MMR Vaccine, Thimerosal And      Late-Onset Autism

(Autistic Enterocolitis)  -  Review Of Evidence Of Vaccine/Autism Links

 

Briefing Note

 

David Thrower    

July 2004 

 


 

Contents

 

Executive Summary

 

Part A:     A Novel Syndrome

1.       What Is Acquired Autism/Autistic Enterocolitis

2.       The New Syndrome

 

Part B:     The Costs of Autism

3.      The Financial Costs  -  Autism Is Costing The Taxpayer £$Billions

4.      Overall Cost Estimates

5.       Failure to Monitor Increases In UK Autism Numbers

6.     “Now Almost Everyone Knows Someone Who’s Autistic”

7.       Is Autism Increasing Due To Changes In Criteria?

8.       Autistic Disorder

9.       Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS)

10.     Asperger’s

11.     University of Cambridge Research

12.     University of Sunderland Research

13.     UK National Autistic Society Estimates

14.     Report by Fiona Loynes for UK All Party Parliamentary Group, Dec. 2001

15.     Report, “Autism In Schools”, UK National Autistic Society May 2002

16.     Is Autism Increasing?  -  Some Recent Official UK Pronouncements

17.     Autism In The USA

18.     Autism Elsewhere

 

Part C:     MMR

19.    The Introduction of MMR

20.     Recognised Adverse Reactions to MMR

21.     US Vaccine Adverse Events Reporting System

22.    Contraindications To Receiving MMR

23.    The UK Department of Health’s Position over MMR and Autism

24.     Single Vaccines In The UK

25.     Measles In The UK

26.     Promotion of MMR In The UK After Wakefield “Early Report” Controversy

27.     Position of the US Center For Disease Control on MMR/Autism

28.     The Parents Have Seen What They’ve Seen.....

 

Part D:     The Thimerosal/Thiomersal* Issue

(*the two terms are interchangeable)

29.     Thimerosal’s Possible Role

30.     Joint Statement by American Acad. Of Ped./Pub. H.  Service, July 1999

31.     Removal of Thimerosal

32.     Waters & Kraus Press Release, 2002

33.     US Use of Thimerosal - Statement by Dr. Geier, 2004

34.     UK Vaccines With Thimerosal

35.     UK Med. and Healthcare Regulatory Agency Position on Thimerosal

36.     UK Joint Committee on Vaccination * Immunisation Position on Thimerosal

37.     US CDC Thimerosal Studies

38.     Report, “Mercury In Medicines”, US Committee on Govt. Reform 2003

39.     Letter to Congress by the US Office of Special Counsel, 2004

40.     California Votes To Ban Thimerosal, June 2004

 

Part E:     Reviews Questioning the Autism Epidemic

41.     Paper by Fombonne, UK Med. Research Council, Pediatrics, January 2001

42.     Paper by Wing, Centre for Social & Commun. Disorders, London 2002

43.     Position of Dr. B. S. Siegal, University of California, 2002

44.     Study by Croen et al, July 2002

45.     Editorial by Fombonne, J. of the American Medical Asscn., January 2003

46.     Paper by Jick et al, Boston Un. Sch of Med., Pharmacotherapy, Dec 2003

 

Part F:     Evidence That Autism Increases Are Real

47.     Close-Up On California

48.     The MIND Study, California

49.     Close-Up On New Jersey

50.     Atlanta Study, 2003

51.     Paper by Gurney, Fritz et al, Trends on ASD In Minnesota, 2003

52.     Paper by Yazbak, Autism In The US - A Perspective, J of A Phs & Surg 2003

53.     Paper by Yazbak, Autism In Quebec, 2004

 

Part G.     Studies Used To Disprove Any MMR/Thimerosal/Autism Link

54.     Limitations of Epidemiology - A Preface

55.     Stokes et al paper, J of American Medical Assoc. (JAMA), Oct. 1971

56.     Study by Peltola and Heinonen, Lancet, April 1986

57.     Paper by Miller, Miller et al, The Practitioner, January 1989

58.     Gillberg Study, Sweden, British Journal of Psychiatry, 1991

59.     Commentary by Gillberg and Heijbel, Autism, 1998

60.     Letter by Fombonne, Pediatrics, March 1998

61.     UK Committee on Safety of Medicines Study, June 1999

62.     Paper By Taylor, Miller and Farrington, Lancet, June 1999

63.     Paper by Miller & Farrington to US Govt Reform Committee, April 2000

64.     Patja, Peltola et al Study, Finland, Pediatric Infectious Disease J. Dec. 2000

65.     Kaye, Melero-Montez and Jick Study, British Medical Journal, 2000

66.     Dales, Hammer and Smith Study, JAMA, March 2001

67.     De Wilde, Carey & Richards Study, Br. J. of General Practice, March 2001

68.     Davis et al study, Archive Pediatrics Adolescent Medicine, 2001

69.     Further Paper by Farrington, Miller and Taylor, Vaccine Journal, 2001

70.     Fombonne & Chakrabarti Study, Pediatrics, October 2001

71.     Further Paper by Taylor, Miller et al, BMJ.com, February 2002

72.     Review by Donald and Muthu, Bazian Limited, British Medical J. June 2002

73.     Study into Childhood Gastrointestinal Disorders and Autism, August 2002

74.     Madsen et al, Population-Based study, MMR/Autism, Denmark, Nov 2002

75.     Study on Mercury by Pichichero, Lancet, November 2002

76.     Study by Makela et al, Finland, Pediatrics November 2002

77.     Commentary by Nelson & Bauman, Pediatrics March 2003

78      Paper, Madsen et al, Thimerosal/Autism in Denmark, Pediatrics, Sep 2003

79.     Paper by Hviid, Stellfeld et al, Denmark, J of Amer. Med Assoc Oct 2003

80.     Paper by Miller, Taylor et al, Archives of Diseases in Childhood 2003

81.     Paper by Taylor et al, Archives of Diseases in Childhood, 2003

82.     Article by Verstraeten et al, Pediatrics, Nov 2003

83.     Paper by Stehr-Green et al, American J of Preventative Medicine 2003

84.     Paper by DeStefano, Yeargin-Allsopp et al, Pediatrics, January 2004

85.     Paper by Williams et al, Aberdeen University, Neuroimage June 2004

 

Part H:     Reviews Concluding There Is No Evidence Of A Vaccine/Autism Link

86.     Medical Research Council Ad-Hoc Review, March 1998

87.     Presentation by Miller to UK All-Party Parl. Gp on Primary Health, 2000

88.     Medical Research Council Sub-Committee Report, March 2000

89.     Review by US Institute of Medicine, 2001

90.     Review by Strauss & Bigham, Health Canada/Un. Of Br. Columbia, 2001

91.     Elliman, Bedford & Miller Review, Arch. of Dis. in Childhood, Oct. 2001

92.     Medical Research Council Review, July-December 2001

93.     Further Review by US Institute of Medicine, February 2002

94.     Review of the Scottish Executive MMR Expert Group, April 2002

95.     Review by Wilson et al, Arch. of Ped. & Adolescent Med., July 2003

96.     Review by US Institute of Medicine, Washington, February 2004

 

Part J:   The MMR Original Safety Trials Debate

97.    Wakefield & Montgomery “Through A Glass Darkly” (MMR safety-studies)

98.     Dr. Peter Fletcher Commentary, Journal of Adverse Drug Reactions, 2001

99.     Dr. Stephen Dealler Commentary, J. of Adverse Drug Reactions, 2001

100.   Dr. F. E. Yazbak Commentary, Journal of Adverse Drug Reaction, 2001

101.   The Wakefield/Watson/Shattock Rebuttals

102.   The UK Department of Health’s Repudiation of “Through A Glass Darkly”.

 

Part K:  Studies That Point Towards The Plausibility Of Gut/Autism, MMR/Gut/Autism, Thimerosal/Autism and Autoimmunity/Autism Links

103.   Paper by Nelson & Gottshall, Applied Microbiology, May 1967

104.   Paper by Eggers, Klinical Paediatrics, March 1976

105    Weizman, Weizmann et al Study, Am. Journal of Psychiatry, Nov. 1982

106.   Delgiudice-Asch and Hollander Study

107.   Paper by Dr. H. Fudenberg

108.   Paper by Dr. Reed Warren

109.   Warren and Singh Study, Immunogenetics, 1992

110.   Singh, Warren, Odell, Warren and Cole Paper, March 1993

111.   Singh, Warren, Odell et al Study, Brain Behaviour, March 1993

112.   Oleske and Zecca paper

113.   Binstock paper

114.   Anne-Marie Plesner Letter, Lancet, February 1995

115.   Paper by Thompson, Montgomery et al, Lancet, April 1995

116.   Gupta, Aggarwal & Heads Study, J. of Autism and Dev. Disorders, 1996

117.   Montinari, Favoino and Roberto paper, Naples conference May 1996

118.   Auwaerter & Griffin paper, Clin Immunology & Immunopath., May 1996

119.   Cook, Courchesne et al Paper, Molecular Psychiatry, May 1996

120.   Griffin and Hussy Study, Journal of Infectious Diseases, June 1996

121.   Martinez et al Study, Proceedings of National Academy of Sciences, 1997

122.   Paper by Zecca, Graffino et al, Meeting of Nat. Inst. of Health, Sept. 1997

123.   Weibel, Caserta and Evans Study, March 1998

124.   Wakefield et al “Early Report”, Lancet, February 1998

125.   Paper by Montgomery, Morris et al (pub. date/details not yet known)

126.   Sabra, Bellanti and Colon letter, Lancet, July 1998

127.   Further Paper by Singh and Yang, Pharmaceutical Journal, October 1998

128.   Uhlmann, Sheils et al Paper

129.   Bitnun et al Study, Clinical Infectious Diseases Journal, October 1999

130.   Paper by Horvath, Papadimitriou et al, Journal of Pediatrics Nov 1999

131.   Paper by Singh to the US Committee on Govt Reform, April 2000

132.   O’Leary Paper Presented to Congressional Oversight C’ttee, April 2000

133.   Kawashima, Takayuki et al Study, Digestive Dis. and Sciences, April 2000

134.   Confidential Review, Centers for Dis. Control, Simpsonwood, June 2000

135.   Hagenbuch, Kullak-Ublick et al Study, J of Pharm. Exp. Ther., July 2000

136.   Wakefield et al Paper, American J. of Gastroenterology, September 2000

137.   Statement by Professor Walter O. Spitzer, December 2000

138.   Furlano, Anthony et al Study, Journal of Pediatrics, 2001

139.   Study by Jyonouchi, Sun and Le, J. of Allergy & Clin. Immun., Feb. 2001

140.   Study by Jyonouchi, Sun and Le, J of Neuroimmunology, 2001

141.   Paper by Spitzer, Aitken et al, J of Adverse Drug Reactions & Tox., 2001

142.   Paper by Dr. Ken Aitken to the Scottish Society for Autism, 2001

143.   Paper by Imani and Kehoe, Clinical Immunology, September 2001

144.   Paper by Buie, Oasis 2001 Conference for Autism, Portland, US

145.   Paper by Uhlmann, Wakefield et al, J. of Clinical Pathology, Feb. 2002

146.   Paper by Singh and Nelson, February 2002

147.   Review by Wakefield, Pulestone et al, Aliment Pharm. Ther. 2002

148.   Report of Study, Comi et al, Johns Hopkins Hospital, Baltimore, Apr 2002

149.   Paper by Torrente, Ashwood, Day et al, Lancet, May 2002.

150.   Paper to 102nd GM of Am. Soc for Microbiology, Singh et al, May 2002

151.   Study by O’Leary et al to Path Soc of GB and Ireland July 2002

152.  Wakefield Paper Presented to US Govt Reform Committee, June 2002

153.   Paper to US Government Reform Committee by Dr Krigsman, June 2002

154.   Unpublished Research by Shattock, Un. of Sunderland, June 2002

155.   Paper by Sheils, Smyth, Martin & O’Leary, Trinity College Dublin, 2002

156.   Paper by Dr. Vijendra Singh, Utah State University, August 2002

157.   Paper by Finegold, Molitoris, Song, J. Of Clin. Infect. Dis., Sept 2002

158.   Further paper, Jyonouchi, Sun & Itokazu, Un. of Minnesota, Oct 2002

159.   Paper, Treatment of Late Onset Autism, Matarazzo, Un. Sao Paulo, Nov 2002

160.   Paper by Makani, Gollapudi et al, Genes & Immunity, 2002

161.   Paper by Westphal, Asgari et al, Arch of Toxicology, August 2002

162.   Unpublished letter by Wakefield to New Eng. J. of Medicine, Nov 2002

163.   Study by Croonenberghs et al, University of Antwerp, December 2002

164.   Paper by Singh and Jensen, Pediatric Neurology 2003

165.   Paper by Geier & Geier, Soc. for Experimental Biology & Med. 2003

166.   Study by Geier and Geier, International Pediatrics, May 2003

167.   Further Paper by Geier & Geier, Ped. Rehabilitation, Apr-June 2003

168.   Further Paper by Geier & Geier, J of Am Phys and Surg, Spring 2003

169.   Paper by Bradstreet, Geier et al, J of Am Phy and Surg Summer 2003

170.   Letter by Geier & Geier, J of Am Phys. & Surgeons, Summer 2003

171.   Paper by Via, Nguyen et al, Envir. Health Perspectives August 2003

172.   Paper by Sweeten, Bowyer et al, Pediatrics, November 2003

173.   Paper by Ashwood, Murch et al, J of Clinical Immunology, November 2003

174.   Study by Ueha-Ashibishi, Oyama et al, Toxicology, Jan 2004

175.   Paper by Singh, presented to the Inst. of Medicine, Washington, Feb 2004

176.   Paper by Bradstreet, Inst of Medicine, Washington, Feb 2004

177.   Paper by Bradstreet, O’Leary et al, Inst of Medicine, Feb 2004

178.   Further Paper by Bradstreet, Institute of Medicine, Feb 2004

179.   Presentation by Geier and Geier to the Institute of Medicine, Feb 2004

180.   Paper by De Water et al, MIND Institute, U of Calif at Davis May 2004

181.   Paper by Hornig, Chian, Lipkin et al, Molecular Psychiatry June 2004

182.   Study by Waly, Olteanu, Deth et al, J of Molecular Psychiatry April 2004

183.   Paper by Torrente, Anthony et al, Am. J of Gastroenterology, April 2004

184.   Presentation b Prof. Boyd Haley, Canada Autism Conference, April 2004

185.   Paper by Bradstreet, Dahr et al, J of Am Phy & Surg Summer 2004

 

Part L:     Other Relevant Papers

186.   US Developmental Delay Registry Report, 1994

187.   Stratton et al Study, National Academy Press, 1994

188.   Paper by Carbone.

189.   Iizuka, Saito et al Study, Gut, May 2001 (Mumps Study)

190.   Statement by Spitzer, US House of Repres. Govt Reform C’ttee, April 2001  

191.   Statement by Dr. Jefferson, Cochrane Collaboration, Oxford, October 2002

192.   Paper by Sweeten et al, Pediatrics 2003

193.   Paper by Blaycock, JANA, Winter 2003

194.   Paper by Singh and Rivas, Jan 2004

 

Part M:     Future Papers Investigating A Link/Increased Prevalence

195.    Fombonne et al Study, London

196.    Charman et al Study, London

197.    Study by Professor Andrew Hall, London

198.    Study by Takahashi et al, Tokyo

199.    Study by Rall, Fox Chase Cancer Center, US

200.    Studies Commissioned by the US Center for Disease Control

201     UK National Institute for Biological Standards and Control Study

202.    Study by University of California at Davis into Environmental Factors

203.    Study by Afzal et al, February 2003

204 .   Other UK Studies funded by the Medical Research Council

205.    Study by Autism Center, Un. of Med. & Dentistry, New Jersey, US

206.    Study by Center for Disease Control, New Jersey, US

207.    Study by Robert Wood Johnson Medical School, New Brunswick, US

208.    Survey by New Jersey Answers for Autism

209.    Columbia University (Lipkin et al) Autism Birth Cohort Study

 

Part N:     Flawed UK Regulatory and Monitoring Systems

210.    Fighting Measles, Missing Autism, Overlooking Damage?

211.    Has the UK Medicines Control Agency Missed the Syndrome?

212.    Further Statement by Dr. Jefferson, Cochrane Collaboration, Mar 2004 

213.    Has The UK Committee on Safety of Medicines Modified MMR Vaccine?

214.    UK Department of Health Re-Launch of MMR, January 2001   

215.    The Search For Alternatives To MMR

 

Part P: UK and US Political Initiatives

216.     UK House of Commons Health Committee, Westminster

217      UK All Party Parliamentary Group on Autism, Westminster

218.     Scottish Parliament, Edinburgh

219.     UK Liberal Democrats

220.     UK Conservatives

221.     US House of Representatives Government Reform Committee

 

Part Q:     Litigation

222.     UK Legal Action

223.     UK Vaccine Damage Payment Scheme

224.     US Vaccine Injury Compensation Scheme (VICP)

225.     Families Taking Legal Action in the US over Thimerosal and Autism

226.     US Government Attempts To Block The Thimerosal/Autism Litigation

227.     MMR Litigation In Ireland

228.     MMR Litigation in Japan

229.     Litigation Elsewhere

 

Part R:     Some Conclusions and Some Unanswered Questions

230.     Some Broad Conclusions

231.     Some Unanswered Questions

 

 EXECUTIVE SUMMARY

 

?         This note  -  which has been put together by the parent of a child who became autistic after immunisation  -  sets out the concerns of parents whose children have degenerated into an acquired-autistic state after MMR or other vaccines, and attempts to summarize the debate over thimerosal (or thiomersal) preservative used in vaccines other than MMR, and to highlight possible links between this mercury-based preservative and autism. It is possible that the MMR and thimerosal factors overlap in the cause of late-onset degenerative autism.

 

?         These are immense and complex subjects. This briefing does not attempt to cover every single piece of the available scientific literature for or against an MMR/autism or thimerosal/autism link, but it reviews about one hundred of the most recent, most pivotal, or most frequently-quoted studies and papers.

 

?         Its key finding is that there has not been a single credible study that can robustly refute the claims of the parents that their children’s acquired autism has been caused by MMR or related vaccines. Each of the studies that seeks to “disprove” an MMR/autism link can be argued to be flawed in design or ambiguous in results. These flaws are discussed in detail in the text.

 

?         It also notes that all but one of the studies that seek to disprove an MMR/autism or a thimerosal/autism link did not look at the actual children themselves, but rather were based upon statistical analyses of the medical records of the wider population. Such epidemiological studies are not appropriate to the identification of relatively-rare adverse outcomes.

 

?         Such studies also fail to address the problem  -  what was it that damaged the specific children that became autistic after MMR or thimerosal-containing vaccines?

 

?         The one MMR study that has both claimed there is no MMR/autism link and also actually looked at information extracted from the medical records of a sub-set of UK damaged children was unable to prove or refute the suggested association with MMR on the basis of the information available  -  although it went on, despite this, to insist that MMR was safe. And  -  note  -  this was still not a clinical study. No children were actually examined.

 

?         Parents who have scrutinised the studies quoted by the Department of Health as “proof” of there being no link between MMR or thiomersal and autism have found that such studies crumble away easily when pressed. To give just one example, the Finnish study by Patja, Peltola et al was very loudly heralded at the start of 2001 by the UK Department of Health as convincing and conclusive proof that MMR was safe. After intense critical scrutiny by parents and media, by the end of 2001 the Medical Research Council was forced to admit that Patja, Peltola et al’s original 1998 paper “did not examine the relationship of MMR and autistic spectrum disorders.....and does not therefore provide useful evidence on this point.” Of the subsequent paper by Patja, Peltola et al, the MRC admitted: “The findings need to be interpreted with some caution, as cases of autistic spectrum disorder or bowel disorders not considered at the time attributable to MMR would not necessarily have been reported”. Quite a retreat. Yet the study still continues to be regularly quoted by medical commentators and professionals as “proof” that MMR is safe.

 

?         In contrast, the parents find that there is a considerable, and growing, number of studies that suggest that MMR and/or thimerosal preservative (routinely used in very many vaccines until very recently, and still in widespread use in 2004) could be causing acquired autism (or “autistic enterocolitis”) in significant numbers of children.

 

?         Contrary to the claims of the authorities, particularly in the UK, not all of these studies originate from only one group of researchers (the former Wakefield team at the Royal Free Hospital London, and then Dr. Wakefield since his departure), as has sometimes been asserted by those who defend MMR. The studies that point to a link have involved a growing number of research teams, in several countries. Other studies, whilst not specifically targeting MMR or thimerosal-containing vaccines, offer further clues as to what may be happening, and are consistent with an MMR and/or thimerosal involvement.

 

?         Furthermore, many of the studies that suggest that there is an MMR/autism or a thimerosal/autism link are based upon the scientific analysis of data gathered from detailed individual medical examination, and upon medical samples taken from the children concerned. These are the studies that actually seek to address the two key questions, “what is the damage sustained by this specific child, and what exactly precipitated the damage to this specific child?”.

 

?         A “house of cards” has thus been constructed by the UK Department of Health, the US Government health system and by other authorities and commentators in the medical establishment over the past five years, with repeated assurances being given to the public, but with these being based upon a lop-sided, highly partisan and culpably selective gathering and interpretation of the available evidence.

 

?         This briefing note also finds that there are other related concerns  -  from the regulatory bodies themselves  -  about the risk of permanent developmental damage from thimerosal-containing (or thiomersal-containing) vaccines, though it is not yet completely understood as to how these problems are directly interlinked biologically to the MMR/autism problems (we are told that MMR in itself does not contain thimerosal). Class-action lawsuits are now under way in the US (see later sections) over thimerosal/thiomersal and autism, just as they have been (or still are) in the UK and Ireland over MMR and autism.

 

?         Although complete and precise scientific proof of how the children have been damaged by vaccines and become autistic is still emerging, there have been numerous vital clues over the past six years and more  -  clues that all too often have been ignored, or, worse still, have been rejected out of hand by the authorities.

 

?         The medical establishment has repeatedly asked itself the wrong question. It has asked itself “Is MMR safe?”, and “is thimerosal safe?”, hoping for an affirmative answer. In contrast, researchers and parents have asked two very different questions: “What precisely is wrong with this child?”, and “Why did this child change from being healthy to being autistic?”. It is answering these latter two questions that should be the key issue.

 

?         The safety trials of MMR were undoubtedly very poor. That is an established fact. For the thimerosal issue, the picture is even more stark. The product appears to have had no proper safety trials since its introduction about 75 years ago, and its use appears to have lacked any appropriate back-checks on safety.

 

?         The children that have been damaged have had their lives ruined. They were previously completely healthy. They now have seventy or eighty years of mental handicap ahead. Whether their sacrifice is justified in the interests of wider public health is not the point at issue. What is at issue is, what changed for these children, through what processes, involving what susceptibility factors and trigger factors. And how can further cases of damage be headed-off?

 

?         This briefing note also poses a number of unanswered questions about MMR, about thimerosal,  and about the children that are believed to have been severely damaged by vaccine administration. The damage involved is not confined to regressive autism.

 

?         Finally, it is emphasized that this note is the result of a search of the published (and sometimes unpublished) studies and other information. It does not offer medical advice. Parents considering vaccinating their children with MMR or with thimerosal-containing vaccines must form their own conclusions as to whether to proceed, and are urged to gather the maximum amount of hard information before making their own choice. It is hoped that this Briefing Note offers a useful start, and is useful for journalists.

 

PART A

 

A NOVEL SYNDROME

 

1:     What Is Acquired Autism/Autistic Enterocolitis?

 

?         Autism is not an illness in itself, so much as a manifestation of a dysfunction in certain parts of the central nervous system, particularly affecting language, cognitive and intellectual development and the ability to relate to others. It is an effect, and a consequence, not a cause in itself. Everything has a cause. Autism is not some mysterious illness that comes out of the sky, to strike children at random. It is a global term, all too loose, to describe a set of characteristics.

 

?         The “classic” form of autism was first described by Dr. Leo Kanner. These children were different from normally-developing children from birth.

 

?         However, a very different form of autism, formerly a minority variant, has now begun to predominate. In this, children develop normally, passing all their developmental milestones, and then later acquire an autistic-like condition. They lose their previously-demonstrated speech, learned behaviour and social skills. In effect, they dissolve into a state of mental impairment, of varying severity. Often the damage is severe or very severe, and usually the damage appears to be permanent, although some remedial treatments are claimed to be able to reverse some aspects of damage to a modest degree.

 

?         This late onset of autism typically follows the receipt of MMR vaccination, but also appears to sometimes follow measles-containing vaccines such as monovalent (so-called “single”) vaccine, or measles-rubella (MR) vaccine, and sometimes other vaccines such as DPT (diptheria-pertussis-tetanus).

 

?         It does not necessarily occur immediately after MMR  -  onset of autism is not in any case an “acute” reaction  -  and there are now grounds for believing that onset following vaccination may be very gradual indeed, spread over at least many weeks, more probably several or many months, or even in some cases several years. The rate of deterioration seems to vary considerably. It has been a consistent error of the medical authorities to view autism as an alleged acute, immediate, reaction, although many parents have certainly reported than some form of immediate or near-immediate (within 24 hours) adverse reactions, such as high-pitched screaming and high temperatures, have occurred. Some parents have reported a rapid change in their child’s behaviour, whereas others have seen a slower decline. Typically, the child’s mood has changed, they have become quiet and withdrawn, speech has been lost and skills have vanished. Sleep patterns have often disintegrated.

 

?         Crucially, the onset of this acquired form of regressive autism is accompanied by other visible and associated physical manifestations of problems. These include bright red ears and dark rings under the eyes after certain foods, acute gluten and casein intolerances, prolonged hyperactivity, night sweating and loss of temperature control, and chronically poor sleep patterns.

 

?         The arrival of these problems and the degeneration of the child into autism as a “package” strongly suggests that they are interconnected

 

?         The timing of onset following vaccination  -  not just MMR  -  is described by the UK Department of Health as a coincidence. Their argument is that autism is “noticed” around this time, because this is a time when child development is most rapid, and therefore any failure most noticeable. The thinking behind this stance appears to be that either autism was always there, all along, or that it is akin to some sort of delayed-action genetic “bomb”, primed in certain individuals to detonate just after receipt of MMR or thimerosal-containing vaccines, or around that time.

 

?         The gross implausibility of this argument, that it is highly unlikely in the extreme that previous problems would have been missed, and at a time where children receive constant devoted attention and close scrutiny regarding their development, is ignored. The concept that genetics alone could be responsible for sudden devastating decline in a developing infant is equally implausible.

 

?         Photographic and video evidence, together with child health and developmental records and the accounts of relatives, friends and visitors, that contradicts the authorities’ arguments, is also routinely ignored, without even a superficial investigation to verify their accuracy.

 

?         However, very significantly, much older children have also degenerated into autism after MMR or other vaccination. If degeneration in affected children always follows immunisation with MMR or measles-containing vaccine, regardless of the age of the child, then it implies that the link is not coincidental.

 

?         Also, no cases are known, at least to campaigning parents, of any children who have rapidly become autistic just before MMR or thimerosal-containing vaccines. This clearly implies that such cases are much fewer in number.

 

?         Also, it is not simply a failure to develop. The children have developed normally, then inexplicably acquired their autistic state. This protracted event has been directly observed by parents and relatives, and in many cases recorded on photographs and video footage.

 

?         There is also the issue of double-regression, where children have been normal, have been vaccinated, have regressed, have made some remedial progress, have been re-vaccinated (as a booster) and have severely regressed again. This principle is known as challenge-rechallenge. The US Institute of Medicine has stated that evidence of challenge-rechallenge would constitute powerful support for a causal link between vaccines and regressive autism. There are many UK children (and presumably US children, too) who offer such evidence, but the IoM has not yet accepted that its self-declared criteria has been fulfilled.

 

?         No credible alternative explanation for why a previously-healthy child should become severely autistic has been put forward. The unheralded acquisition of a state of severe disability, in a substantial number of hitherto-healthy children, has to have a significant causal trigger. A growing number of scientists, as well as parents, believe that the trigger is either MMR, or thimerosal, or both acting in synergy.

 

?         Undoubtedly there are other factors involved, pointing to a predisposition of certain children to be vulnerable to damage, of varying severity. Research should be trying to pinpoint those factors, but patently is not. Research is being held up by the refusal of the medical establishment in the UK and US to recognise the problem, or even to recognise the reality of a steep increase in autism.

 

?         Also coinciding with the late onset of autism in many of the children (or other severe damage  -  autism is not the only manifestation of there being a problem), has come gastrointestinal problems such as alternating bouts of diarrhoea and constipation, chronic abdominal pains and bloating.

 

?         Examination of children, initially but not exclusively at the Royal Free Hospital, London, has identified a novel form of inflammatory bowel disease, ileal-lymphoid nodular hyperplasia. This has emerged after ileocolonoscopy of affected children and analysis of samples. The pioneer research the Royal Free has now been confirmed by researchers at other centres in Ireland and the US.

 

?         The simultaneous onset of these problems after a normal early development suggests that it is highly likely that these other elements are linked into the biological explanatory sequence of autism, notably through the pathway of gut damage and either the penetration of the blood-brain barrier or the triggering of some other process, such as serious myelin damage (in basic terms, the myelin sheath is the “insulation” around the neurons or “wires” of the brain).

 

?         Research reported by Dr. Jeff Bradstreet to the US Institute of Medicine on 9th February 2004 found that, when the cerebrospinal fluid of 28 regressive-autistic children was analysed, measles virus was found in 19 of the 28 cases. When 37 non-autistic control-group children were analysed, only one child was found to have measles virus. All 65 of these children had received MMR, and none had any recorded history of wild measles infection. This more recent research is powerful statistical evidence of a measles virus complicity in the pathogenesis of regressive autism. This research therefore strongly endorses the anecdotal evidence of the parents, that their children became autistic after MMR. For many children, MMR thus remains the prime suspect.

 

2:     The New Syndrome

 

This is a very brief summary of the new syndrome of autistic enterocolitis:

 

?         In a 200-strong cohort of children examined through ileocolonoscopy at the Royal Free Hospital, London, an almost 100% incidence of ileal-lymphoid nodular hyperplasia has been found. This condition manifests itself as swollen lumps throughout the intestinal tissue of autistic children. The condition is very rare in non-autistic children.

 

?         The condition is believed to have developed in each case in the period following MMR immunisation

 

?         Because of the swollen and hyperplasic condition of the intestinal wall, undigested toxins , having not been stopped by either the intestine or the liver (which can also be damaged) may then be able to attack the central nervous system. The evidence for the complete pathway of damage is uncertain at present, due to lack of research.

 

?         An alternative pathway of damage may be that the virus(es) in the vaccine, or other constituents of the vaccine, may be inflicting the actual damage, or interfering with the brain’s further development by damaging myelinisation. Comprehensive studies to determine this have also yet to be undertaken.

 

?         It is also possible that thimerosal, a mercury-based preservative that has been routinely used in a number of vaccines, may have played a role. The resultant damage closely resembles that of mercury poisoning. Again, adequate research has not yet been done.

 

?         Damage may in the event be via a combination of these pathways.

 

PART B

 

THE COSTS OF AUTISM

 

3:     The Financial Costs  -  Autism Is Costing The Taxpayer £££££££$$$$$$$$Billions

 

Quite apart from the immense social costs of autism for individual families, there are the huge financial costs. Autism effects every UK and US taxpayer, not just the families with the children. In the UK, the costs comprise:

 

?         Health costs  -  specialist hospital visits, GP visits, prescriptions, exclusion diet costs  -  passed on to the taxpayer

 

?         Major education costs  -  special schools, extra teachers, extra teaching assistants, extra training, management  -  passed on to the taxpayer

 

?         Transport costs for schooling and respite  -  taxis plus drivers and escorts, plus local authority management costs, plus environmental/congestion costs of extra traffic  -  passed on to the taxpayer

 

?         Significant childhood social services costs  -  respite care staff costs, management, inspection, reviews  -  passed on to the taxpayer

 

?         Later special transport costs in adult life (during lifelong care)  -  funded by the taxpayer, as the person with autism will almost certainly have no income

 

?         The immense costs of sheltered accommodation during adult life (lifelong costs), again including social services, management, inspection, and also including furniture and other allowances, all passed on to the taxpayer

 

?         The immense loss of earnings of the affected person (lifelong)

 

?         The loss to the Government of their national tax revenues (lifelong)

 

?         The loss to local government of their Council Tax revenues (lifelong)

 

?         Loss of earnings of parents whilst acting as carers

 

?         Loss of the parents’ tax revenues whilst caring

 

?         Carers allowances (paid to parents when they are acting as carers), the costs of which are passed on to the taxpayer

 

?         Disability living allowances, often at the higher rate (lifelong), including care and mobility components, passed on to the taxpayer

 

?         Incapacity benefit (lifelong beyond age 16), passed on to the taxpayer

 

?         Wider economic costs  -  other losses of gross domestic product and other non-financial contributions to the national economy

 

It would be interesting to know if the UK (or US) Treasury had a view on these costs, and whether sufficient resources were being devoted to investigating acquired autism and other forms of autism, as they represent a massive loss to the local and national taxpayer and the national economy. These costs will grow as more and more children become autistic and as more of the existing children reach adulthood and leave home. The affected people almost certainly won’t be paying these costs as children, nor even as adults, as they almost certainly won’t have any income. And once the children reach adulthood, the parents won’t be paying them, either.

 

As these costs soar, the question becomes, “is autism too important to be left to the Department of Health, a Department that has done virtually nothing to investigate its causes”?  -  or to its counterparts in the US and elsewhere? Is this just a private matter for the medical community, or a matter for a wider audience? And, for the medical safety regulators, “who guards the guards”? Does a Minister control his/her advisers, or do his/her advisers control the Minister?

 

4:     Overall Cost Estimates

 

In June 2000 a study for the UK Mental Health Foundation found that

 

?         the annual costs of autistic disorder in the UK were at least £1 billion

 

?         individual lifetime costs per child affected could run to £2.94 million each.

 

The full costs, taking into account wider economic costs, are probably considerably higher still.

 

If one reduces the £2.94m per child by an arbitrary 33%, to allow for the fact that many children are less severely damaged than the maximum, and will thus cost less to care for, one is still facing a bill of £2m for lifelong care, not counting other wider costs such as loss of tax revenues from the autistic person an (when their parents care for them) their carers, plus other costs such as carers’ allowances (a UK scheme). The degree of severity and precise costings could be debated at length, but are clearly extremely large for severe cases.

 

Another way of looking at it is to compare the UK with the US, which has hard State-collected data. According to the Individuals With Disabilities Education Act data, the US autism numbers (with four times the population) stood at 120,000 in early 2003 (amongst 6-21 year olds in full time education).

 

If UK cases currently run to around a quarter of this figure, 30,000 to 35,000, then total economic costs for the UK could be immense. A reasonable estimate would be that 35,000 cases would cost the UK taxpayer somewhere between £35 billion and £100 billion spread over perhaps seven decades, or between £500m and £1.4 billion per annum. A mid-range answer probably lies in the £20 billion to £40 billion-plus range, spread over five to six decades, and even that latter figure works out at £700 million per year. And that is only for the UK.

 

Even if these costs are being seriously overestimated here, they are still immense. And they could represent an underestimate, especially if there is economic damage from the milder cases that are probably not included in the statistics. There is also the prospect of cases being added to the total, all the time, now. Any annual increase in cases of, say, ten per cent would lead to all these estimates having to be re-doubled a decade on.

 

And this is wholly irrespective of any MMR-autism or thimerosal-autism link being proved, because the children already exist, even if the cause of their illness remains disputed. The children are out there, now, and these bills are being passed to the taxpayer, now, today. The costs meter is already running, but the immense scale of the bill is partly obscured by it being spread amongst many central and local government (or Federal and State) budget headings, and amongst numerous lesser authorities.

 

5.     Failure To Monitor Increases In UK Autism Numbers

 

?         There has been a consistent argument on the part of the authorities, and those seeking to defend MMR, that the apparent rise in autism may be largely a matter of better recognition. This has received some backing from autism researchers. But where hard UK or US data is available, increases are far too steep, and in far too short a timescale, to be credibly ascribed to better recognition alone..

 

?         For this to be “better recognition” or “improved diagnosis”, this would have required these children to have been missed, simultaneously, by their parents, their relatives, their doctors and their teachers in the past This is simply not credible. For example, the increase in autism 1992-99 in Wakefield, West Yorkshire, UK, local education authority was from 5 cases to 111 cases. If increased autism is down to better recognition, it would mean that, back in 1992, there really were 111 cases, but only 5 were recognised, and the remaining 106 were missed, and by all the parties  -  parents, doctors, health visitors, teachers  -  concerned. This is completely implausible.

 

?         Undoubtedly there has been some degree of better recognition and reclassification, following introduction of ICD-10 (international classification of diseases/disorders) criteria in 1992, and DSM-IV (diagnostic statistics manual) criteria in 1995. But this will account for only a minority of the growth.

 

?         The UK Department of Health has failed to monitor autism, and is still failing to (despite a specific 1997 recommendation of the House of Commons Health Committee to do so). Is it now afraid of what it might find? If it does decide to monitor autism, will it find that numbers are high and then claim it has always historically been so?

 

?         UK Health Boards/Authorities are also failing to monitor autism locally. Health Boards/Authorities have little data and no consistent approach. At the health authority level, official figures vary wildly, by factor of 300-fold, i.e. 300-times (not 300%). The data is an extraordinary mess.

 

?         In fact, most UK data is actually non-existent. In the year 2000, only 1 in 6 UK Boards/Authorities had any credible figures at all. Most used estimates from textbooks.

 

?         The Scottish schools census now includes autism. The census commenced in 1998. The 1998 figure was around 750, but by year 2000 this had climbed steeply to about 1,250, and by 2002 it stood at approaching 2,200.

 

?         There are other indications of the level of increases: Kaye et al paper (see later) found a sevenfold increase 1988-99 in UK. An unpublished 1999 paper by Dr. Fiona Scott, Autism Research Unit, Cambridge, indicated autism at eleven times the expected level (1 in 174)  -  see later.

 

?         The 2001 Medical Research Council review found autism to be at 1 in 166, many times higher than hitherto thought. Sixteen studies published between 1966 and 1991 found rates of between 1 in 3030 and 1 in 625. A rate of 1 in 166 is nearly four times higher than 1 in 625, itself the highest of these sixteen, and only from a relatively-recent study in 1983. If you take a rate of 1 in 1830 as being the mid-point of these historic rates, then a rate of 1 in 166 is eleven times higher.

 

The repeated official line that the apparent increase is down to better recognition is little more than a counsel of complacency.

 

In December 2002, a Parliamentary Written Question (84502) confirmed that there is now in place a “Good Practice Guidance on Autistic Spectrum Disorders”, in the UK, published by the Government’s Departments of Education & Skills and of Health. This is intended to raise awareness amongst schools and local education authorities. However, it is probably just one of many thousands of such well-intentioned documents, is non-statutory, and is probably lost in the stream of paper raining down on local government from central government.

 

UK schools and local education authorities have a duty to identify, assess and make suitable provision for children with special educational needs. However, there seems to have been no duty upon either the health authorities at the local level or the Department of Health at Government level to improve the data position over autism  -  doubtless to the latter’s relief. Perhaps centrally-collated figures showing steep increases would beg uncomfortable questions as to the causes. The UK Department of Health seems to regard autism as a problem for local education authorities  -  not for the Department.

 

It is understood that from January 2004, a first survey in England will be undertaken of disabilities amongst children receiving special needs education. This will be the UK (England-only) Pupil Level Annual Schools Census (PLASC). English local education authorities and the schools in their areas have to supply data about the numbers of pupils with different types of special educational need, including autistic-spectrum disorders.

 

However, it may be some time before data is available, and obviously it will be several years before any clear trend emerges. Any past steep rise during the 1988-2004 period will therefore of course have been missed, although some idea of increases may be available if data is stratified by age (this is not known at time of writing).

 

6.     “Now Almost Everyone Knows Someone Who’s Autistic”

 

Autism was a very rare condition, but is now almost regarded as commonplace. Very many cases are now of late-onset autism, whereas almost all used to be cases from birth. We have to ask why this is.

 

Some UK research noted the sharp increases in autism in the 1990s. A paper by Powell et al, Department of Public Health and Epidemiology, University of Birmingham, UK, Changes in the Incidence of Childhood Autism and Other Autistic Spectrum Disorders in Pre-School Children from Two Areas of the West Midlands, UK, was published in Developments in Medicine and Child Neurology, September 2000. This looked at the incidence of childhood autism and ASD in pre-school children between 1991 and 1996.

 

The study found that there were year-on-year increases in classical autism during this period of 18%, but for “other ASDs” the annual increase was no less than 55%. But the study then concluded that this was due to clinicians being increasingly able or willing to make a diagnosis. The possibility of an underlying genuine increase, and any follow-on question as to causes, does not appear to have occurred to the study team.

 

But parents of children believe to have been damaged by MMR strongly believe that part of the increase is down to a new phenomena, autistic enterocolitis.

 

It is not the autism of the past. Such a severe acquired regressive syndrome after a normal early childhood would have been noticed at once in the past by parents, and recognised medically, and also reflected in much higher historic rates of prevalence/incidence. Regressive autism used to be a minority variant: Now it is clearly the predominant form, by a very wide margin. Dr. Bernard Rimland, President of the US Autism Research Institute, has concluded, after a thorough analysis of the ARI database: “Late onset autism (starting in the second year) was almost unheard of in the 1950s, 1960s and 1970s. Today, such cases outnumber early onset cases by five to one, with the increase paralleling the increase in required vaccines”.

 

In the parents’ view, there is clear evidence of recent dramatic rates/increases in autism:

 

?         Some UK examples  -  an East Surrey 1/69 rate amongst three year old boys, 1/139 rate amongst three year old boys+girls combined (source: personal communication of 10/6/99 from Caroline Clark, Commissioning Manager, Learning Disability Services, East Surrey Health Authority). The letter from East Surrey stated: “In the remaining half of the District, it is estimated that there are at least 50 children on the autistic spectrum under the age of five. A special needs audit has been undertaken of children aged three by the community paediatrician. This is the age where the paediatrician expects to identify children at the more severe end of the autistic spectrum. Thirty-six children have been identified during the last two years as presenting with autism, of which twenty-nine were between the ages of two and three, with seven children slightly older. The general population is around 2,500 children (born) per year in this part of the District. The prevalence of autism indicated by the audit is 0.72% (1 in 139) but with 1.44% (1 in 69) for young boys.”

 

?         Bromley Autistic Trust figures show a 1990-94 increase of 280% over 1980-84 figures (source: personal communication of 16/9/99 from Miss C. M.  Povey, Services Director, Bromley Autistic Trust)

 

?         A local survey carried out in the Inverness area in 2003 found that 1 in 49 children was on the autistic spectrum.

 

?         Wakefield LEA autism pupils rose from 5 to 111 in seven years (source: survey by David Brown, a specially-seconded headmaster from the Park School, Wakefield, on behalf of Wakefield Local Education Authority, 1999)

 

?         Telford health data up from 4 new cases per year in 1990 to 17 per year 1998 and again 1999 (source: personal communication of 20/11/00 by Dr F. R. J.  Hinde, Consultant Paediatrician, Princess Royal Hospital, Telford)

 

?         As noted, Scottish schools census, repeatedly up year-on-year, and by a large margin each year; from around 750 in 1998 to well over 2000 in 2002 (source: Scottish Annual School Censuses, available from Scottish Education Office, tel 0131 556 8400)

 

The problem isn’t confined to autism. On December 22nd 2002, the (UK) Observer newspaper carried a report on the apparent epidemic of behavioural problems amongst UK schoolchildren. Whilst not autism (the report cited hyperactivity and attention-deficit disorder), the Observer’s report suggested a steep rise in the incidence of problems. Figures obtained by the newspaper suggested that numbers of schoolchildren with attention-deficit disorder (ADD) or attention-deficit hyperactivity disorder (ADHD) had reached 345,000, and that one child in twenty between the ages of 6 and 16 years had one or other condition. The Observer also found out that prescriptions for Ritalin, to counter these disorders, had increased markedly, from 91,100 in 1997 to 208,500 in 2001.

 

In the US, the Brown University Child & Adolescent Behavioural Letter (18(3): 1: 304, 2002) carried the following details:

 

?              A study into attention deficit hyperactivity disorder (ADHD) was undertaken, based on parent and teacher reports concerning 6,099 children in 17 public elementary schools. The study was undertaken by researchers working for the National Institute of Environmental Health Sciences in North Carolina

 

?              When the researchers surveyed parents in a typical county of rural and suburban communities  -  Johnston County, North Carolina  -  the parents reported that more than 15% of boys in grades 1st through 5th had a diagnosis of ADHD, with about 10& (i.e. two-thirds of those diagnosed) receiving medication.

 

Although ADHD is not autism, it may share some common causal pathways, particularly multiple food allergies and gut permeability. The finding is thus of interest to the MMR/autism debate.

 

7.     Is Autism Increasing Due To Changes In Criteria?

 

It has frequently been asserted by Governments, some researchers and elements of the medical establishment that the apparent increases in numbers of children with autism can be ascribed to “looser” criteria for inclusion. This latter point is demonstrably not the case. The criteria have in fact tightened-up.

 

Kanner’s original concept of autism included five diagnostic features:

 

  *     A profound lack of affective contact

 

  *     obsessive desire for the preservation of sameness

 

  *     Fascination for objects

 

  *     mutism or language that does not seem suited to interpersonal communication

 

  *     feats of memory, or skills in performance tests

 

Kanner and Eisenberg, in 1956, emphasized two diagnostic criteria:

 

  *     profound lack of affective contact

 

  *     repetitive ritualistic elaborate behaviour

 

They considered that if these two key features were present, the other typical features would also be found.

 

In 1980, the DSM-III (Diagnostic and Statistical Manual III) criteria were introduced. These included:

 

  *     “pervasive developmental disorder” for the general category of autism

 

  *     “infantile autism”

 

The category of infantile autism was defined as:

 

  *     lack of responsiveness to others

 

  *     language absence or abnormalities

 

  *     resistance to change and/or attachment to objects

 

  *     the absence of schizophrenic features

 

  *     onset before age 30 months

 

In 1994, DSM-IV criteria were introduced. These criteria are more restrictive than DSM-III, and so an increase in numbers between the DSM-III era and the DSM-IV era cannot be explained by looser criteria, as the very opposite is the case. For example, in Washington State, autism numbers actually fell when DSM-IV was introduced.

 

It is worth setting out in detail the criteria for autism and relating autistic-spectrum disorder (ASD) conditions:

 

8.     Autistic Disorder

 

For DSM-IV, a total of six or more items from the following lists of (1), (2) and (3) is necessary, with at least two items having to come from (1), and one each from (2) and (3):

 

(at least two from)

 

(1)     Qualitative impairment in social interaction as manifested by:

 

*     marked impairment in the use of multiple non-verbal behaviours, such as eye-to-eye gaze, facial expression, body postures and gestures to regulate social interaction

 

*     failure to develop peer relationships appropriate to developmental level

 

*     a lack of spontaneous seeking to share enjoyment, interests or achievements with others (eg by a lack of showing, bringing or pointing-out objects of interest

 

*     lack of social or emotional reciprocity

 

(at least one from)

 

(2)     Qualitative impairments in communication, as manifested by at least one of the following:

 

*     delay in, or total lack of, the development of spoken language (not accompanied by an attempt to compensate through alternative modes of communication such as gesture or mime)

 

*     in individuals with adequate speech, marked impairment in the ability to initiate or sustain a conversation with others

 

*     stereotyped and repetitive use of language or idiosyncratic language

 

*     lack of varied, spontaneous make-believe play or social imitative play appropriate to developmental level

 

(at least one from)

 

(3)     Restricted, repetitive and stereotyped patterns of behaviour, interests and activities as manifested by at least one of the following:

 

*     encompassing preoccupation with one or more stereotyped and restricted patterns of interest that is abnormal either in intensity or focus

 

*     apparent inflexible adherence to specific non-functional routines or rituals

 

*     stereotyped and repetitive motor mannerisms (eg had or finger-flapping or twisting or complex whole-body movements)

 

*     persistent preoccupation with parts of objects

 

9.     Pervasive Development Disorder  -  Not Otherwise Specified

 

The DSM-IV criteria also included criteria for “pervasive development disorder-not otherwise specified”, or PDD-NOS. This category applies to cases where there is a severe and pervasive impairment in the development of reciprocal social interaction or verbal and non-verbal communications skills, or when stereotyped behaviour, interests and activities are present, but the criteria are not met for a specific pervasive developmental disorder, or schizophrenia, or schizotypal personality disorder, or avoidant personality disorder.

 

For example, PDD-NOS includes “atypical autism”, presentations that do not meet the criteria for autistic disorder because of late age of onset, atypical symptomatology, or sub-threshold symptomatology, or all of these.

 

10.     Asperger’s

 

The DSM-IV criteria for Asperger’s Disorder (or syndrome) are as follows:

 

Qualitative impairment in social interaction as manifested by at least two of the following:

 

*     marked impairment in the use of multiple non-verbal behaviours such as eye-to-eye gaze, facial expression, body postures and gestures to regulate social interaction

 

*     failure to develop peer relationships appropriate to developmental level

 

*     lack of spontaneous seeking to share enjoyment, interests or achievements with other people

 

*     lack of social or emotional reciprocity

 

Restricted, repetitive and stereotyped patters of behaviour, interests and activities as manifested by at least one of the following:

 

*     encompassing preoccupation with one or more stereotyped and restricted patterns of interest that is abnormal in intensity or focus

 

*     apparently inflexible adherence to specific nonfunctional routines or rituals

 

*     stereotyped and repetitive motor  mannerisms such as had or finger-flapping or twisting, or complex whole-body movements

 

*     persistent preoccupation with parts of objects

 

The disturbance causes clinically-significant impairment in social, occupational or other important areas of functioning. There is no clinically-significant general delay in language, eg single words are used by age two years, communicative phrases used by age three years). There is no clinically-significant delay in cognitive development or in the development of age-appropriate self-help skills, in adaptive behaviour (other than in social interaction) and in curiosity about the environment in childhood. Criteria are not met for another specific pervasive developmental disorder, or schizophrenia.

 

11.     University of Cambridge Research

 

On 18/2/01, the UK Sunday Telegraph reported on research undertaken by Dr. Fiona Scott at the Autism Research Centre at the UK University of Cambridge. The research, Prevalence of Autism Spectrum Conditions in Children Aged 5-11 Years in Cambridgeshire UK, by Scott, Baron-Cohen et al, which is due to be published shortly, was undertaken across schools in Cambridgeshire.

 

The study aimed to establish prevalence of the broader autistic spectrum, including Asperger syndrome in 5-11 year olds in Cambridgeshire, UK. Cases of diagnosed autism spectrum condition in children who were in Cambridgeshire schools and aged 5-11 on 31st December 1999 were sought out using public records, screening instruments, educational psychology and special educational needs coordinator records.

 

It found that:

 

?         One in 175 (58/10,000) children was autistic, whereas previous studies had pointed to a rate of 1 in 2000 (5/10,000)

 

?         This was 11 times higher than the rate of classic autism, but in line with other recent national and international rates for the broader spectrum.

 

?         In responding mainstream schools, the prevalence was 1 in 300. In the responding special schools, the prevalence was 1 in 8.

 

?         Extrapolated across the UK, that would imply 30,000 primary school (age 5-11) children with autism

 

?         The overall sex ratio of the children was 4 to 1 male to female, but in mainstream schools it as 8 to 1.

 

?         Linking these rates to estimated costs of education and care for sufferers would give a figure of as high as £5 billion per year, year after year. The Cambridge autism figures were described as “if anything an under-estimate”. They included only children with a definite clinical diagnosis. Any child who had only been “statemented” (= educational needs-assessed) as autistic, but not yet clinically diagnosed, was not counted

 

?         One in eight children with special educational needs was suffering from some form of autistic spectrum disorder. The increase of actual numbers over previously-assumed numbers would have enormous cost implications for central and local Government

 

?         A year-2000 report for the UK Mental Health Foundation by Professor Martin Knapp for the UK Institute of Psychiatry used the earlier “textbook” rate of autism of 5/10,000 to put the total UK economic cost of autism at £1bn. The Knapp report estimated the lifetime cost of a severely-affected child at £3m, for a high-functioning autism child at £0.8m, and for an Asperger’s syndrome child at £0.5m. The revised £5bn per year estimate is based upon these costs.

 

12.     University of Sunderland Research

 

An unpublished study by the UK University of Sunderland found a tenfold increase in diagnosis of autism, during the years 1989-93.

 

13.     UK National Autistic Society Estimates

 

The NAS issued a factsheet in early 1997 which gave the following prevalence rates:

 

?         People with Kanner syndrome (IQ less than 70)          5/10,000, or 1 in 2,000

 

?         Other spectrum disorders (IQ less than 70)                15/10,000, or 1 in 666

 

?         Asperger’s (IQ 70 or above)                                         36/10,000, or 1 in 278

 

?         Other spectrum disorders (IQ 70 or above)               35/10,000, or 1 in 286

 

Combined total of above four groups                                91/10,000, or 1 in 110

 

The above implies a very high level of autism in the UK, and the previously-described studies seem to bear this out.

 

The NAS reach its 91 in 10,000 or 1 in 110 rate by taking the Wing & Gould study (Camberwell, London) of 1979, which looked at children with an IQ of under 70 and found a rate of 20 per 10,000, and adding this to the study by Ehlers & Gillberg (Sweden) of 1993 which looked at autistic children with an IQ of over 70 and found a rate of 71 per 10,000 (1 in 141).

 

The 91/10,000 rate is thus “merged data”, collected in two different countries and some years apart, and thus needs to be treated with caution, particularly if rates have since been rising further. The Wing & Gould study is now over two decades out of date, and also pre-dates MMR introduction into the UK.

 

14.     Report by Fiona Loynes, UK All-Party Parliamentary Group on Autism, Dec. 2001

 

The purposes of this report included:

 

?         To establish numbers of children with autistic spectrum disorders

 

?         To learn whether UK local education authorities believed there had been a recent increase in the last five years

 

?         To ascertain whether LEAs routinely collected data

 

The findings included the following:

 

?         100 out of 115 LEAs reported an increase in autism in the past five years. Some reported small increases, others reported far higher increases, in one case by 77%.

 

?         The study compared the expected prevalence rate of all autistic spectrum disorders in each LEA (91 in 10,000 or 1 in 110) with the actual recorded number of children with ASD and a Statement of Educational Needs (21 in 10,000 or 1 in 476). If the estimated numbers are correct, then the implication is that 75% of children with autism do not become included in the Statement data, because they have no Statement.

 

?         Only 44 out of the 100 LEAs reporting an increase had actual data. Some of these reported dramatic increases, up to 400% in four years.

 

15.     Report, “Autism In Schools  -  Crisis or Challenge”, National Autistic Society UK, May 2002

 

This report was complied from the findings of a survey carried out in seven local education authorities across England, Wales and Scotland, although the Scottish findings were reported separately. The England and Wales survey involved 373 individual surveys, with a response rate of over 30%, covering a pupil population of 133,000. The study found that:

 

?         1 in 86 children in mainstream schools had special educational needs that were related to ASD.

 

?         The rate of ASD is three times higher in primary than in secondary schools. In primary it is 1 in 80, in secondary it is 1 in 268.

 

?         This is in addition to children with ASD in special schools. In special schools, 1 in 3 children has ASD-related needs.

 

16.     Is Autism Increasing?  -  Some Recent UK Pronouncements

 

These are some recent, and sometimes self-contradicting, statements:

 

?         “There is no good evidence that the frequency of autism has increased since the introduction of MMR” - Tessa Jowell, then Minister for Public Health, October 1997 (personal communication to David Thrower)

 

?         “The true incidence of autism is uncertain” - Sir Kenneth Calman, then Chief Medical Officer, March 1998

 

?         The apparent rise in autism in the UK began more than ten years before the introduction of MMR” - Tessa Jowell, in June 1998

 

?         “Rates of autism are rising, but not because of MMR” (Committee on Safety of Medicines, June 1999)

 

?         “There is no robust data on the prevalence of autism before and after MMR’s introduction” - Brent Taylor, in a June 1999 study heavily quoted by the Department of Health

 

?         “Numbers of cases of autism are rising, but the reason for this is unclear” - John Hutton, Minister for Public Health, December 2000

 

?         Methodological differences between studies, changes in diagnostic practice and public and professional awareness are likely causes of increases in prevalence. Whether these factors are sufficient to account for increased numbers of identified individuals, or whether there has been a rise in actual numbers, is as yet unclear” - Medical Research Council 2001 review, quoted by the Scottish Parliament Expert Group May 2002.

 

?         “Two thirds of (surveyed) teachers felt that there were more children with ASD now than five years ago. This (is) consistent across age groups and in all types of education provision, special and mainstream” (Report of the National Autistic Society, May 2002)

 

?         “The vast majority of the increase is due to the fact that we’re much better at detecting autism now (and) we include many more things in the spectrum for autistic spectrum disorders.....There’s a far wider spectrum, so that’s one of the factors.” - Dr. Stephen Ladyman, Health Minister for England, in Epolitix, 14th October 2003

 

But then Dr. Ladyman hedged his bets a little.....

 

?              “And underlying that, I think there may well be some sort of underlying increase in the number as well.....But what I am as certain of as I can be is that it has nothing to do with MMR and there is no reliable piece of science that links MMR and autism.”

 

  and

 

?              “In my view, it is clear from the literature available that more people with autism have bowel disorders compared to the rest of the population” (extract from All Party Parliamentary Group On Autism minutes, address by the Minister).

 

17.     Autism In The USA

 

The UK Department of Health is fond of saying how MMR is safely used in 32 countries, including the USA, as though its use elsewhere is proof, in itself, that it is safe. Recent claims have even referred to 100 countries. A similar attitude prevails over thimerosal.

 

But the USA, at least, has clear evidence of an autism epidemic. Other countries may also be becoming aware of increases, for example Finland, where a 400% increase in cases has been alleged since was MMR introduced.

 

The US has IDEA (Individuals with Disabilities Education Act). This picks up numbers of schoolchildren with developmental problems. Autistic pupils ages 6-21 are up from 12,222 to 118,602 between 1992-1993 and 2002-2003 (Source: US IDEA State data).

 

Since the introduction of the more restrictive DSM-IV criteria from 1994 onwards, the rise in US numbers has continued unabated:

 

year

95-96

96-97

97-98

98-99

99-00

00-01

01-02

02-03

cases

28,813

34,082

42,487

53,561

65,391

78,717

97,847

118,602

 

(source: Individuals With Disabilities Education Act)

 

?         To the above total also has to be added the further cases of autism amongst children aged 3-5 years. As at year 2000, this was 15,581 (this number will have since increased further).

 

?         There were huge increases in some States between 1992-1993 and 2002-2003  -  up 968% in Connecticut, 779% in Florida, 1,131% (repeat: one thousand one hundred and thirty-one per cent) in Idaho, 1,086% in Kansas, 1,291% in Minnesota, all in just ten years (Source: US State data, Individuals with Disabilities Education Act). The rises have continued into 2004.

 

?         Many of the increases in individual States can only be described as alarming. A selection of States is included here:

 

  Florida, ages 6-21

 

Year

Number of diagnosed cases in IDEA

1999-2000

3,114

2000-2001

3,626

2001-2002

4,328

2002-2003

5,117

2003-2004

5,915

 

  Illinois, ages 3-5

 

Year

Number of diagnosed cases

2000-01

670

2001-02

660

2002-03

841

2003-04

956

 

  Illinois, ages 6-21

 

Year

Number of diagnosed cases

2000-01

3,103

2001-02

3,802

2002-03

5,080

2003-04

6,005

 

  Indiana, ages 3-5

 

Year

Number of diagnosed cases

2000-01

456

2001-02

533

2002-03

632

2003-04

678

 

  Indiana, ages 6-21

 

Year

Number of diagnosed cases

2000-01

2,621

2001-02

3,262

2002-03

3,975

2003-04

4,749

 

  Massachusetts, ages 3-5

 

Year

Number of diagnosed cases

2000-01

231

2001-02

770

2002-03

887

2003-04

1,080

 

  Massachusetts, ages 6-21

 

Year

Number of diagnosed cases

2000-01

575

2001-02

2,681

2002-03

3,193

2003-04

4,007

 

  Minnesota, ages 3-5

 

Year

Number of diagnosed cases

2000-01

345

2001-02

452

2002-03

618

2003-04

762

 

  Minnesota, ages 6-21

 

Year

Number of diagnosed cases

2000-01

2,448

2001-02

3,270

2002-03

4,116

2003-04

5,076

 

  New Jersey, ages 3-5

 

Year

Number of diagnosed cases

2000-01

397

2001-02

447

2002-03

464

2003-04

570

 

  New Jersey, ages 6-21

 

Year

Number of diagnosed cases

2000-01

2,925

2001-02

3,526

2002-03

4,180

2003-04

4,933

 

  Ohio, ages 3-5

 

Year

Number of diagnosed cases

2000-01

326

2001-02

334

2002-03

334

2003-04

344

 

  (note: these figures show a minimal increase, and are out of line with other States. The reason for this is not known).

 

  Ohio, ages 6-21

 

Year

Number of diagnosed cases

2000-01

2,217

2001-02

3,057

2002-03

4,017

2003-04

5,146

 

  Oregon, ages 3-5

 

Year

Number of Diagnosed Cases

2000-01

429

2001-02

506

2002-03

588

2003-04

630

 

  Oregon, ages 6-21

 

Year

Number of diagnosed cases

2000-01

2,516

2001-02

2,847

2002-03

3,339

2003-04

3,760

 

  Virginia, ages 3-5

 

Year

Number of diagnosed cases

2000-01

222

2001-02

266

2002-03

363

2003-04

418

 

  Virgina, ages 6-21

 

Year

Number of diagnosed cases

2000-01

1,983

2001-02

2,365

2002-03

2,966

2003-04

3,533

 

  Wisconsin, ages 3-5

 

Year

Number of diagnosed cases

2000-01

306

2001-02

334

2002-03

340

2003-04

410

 

  Wisconsin, ages 6-21

 

Year

Number of diagnosed cases

2000-01

1,823

2001-02

2,247

2002-03

2,739

2003-04

3,259

 

 

  (note: increases in the younger ages are often lower than increases in the older ages, due to growing delays in diagnosis)

 

?         It is also interesting that individual towns such as Round Rock, Texas, are reported to be up from 6 cases to 115 cases in eight years  -  very much like Wakefield Local Education Authority in West Yorkshire UK (up from 5 to 111 in seven years). This suggests that UK increases may very closely match those in the USA.

 

?         It has been alleged that Brick Township (New Jersey) has manifested an “autism cluster”. Some 40 of Brick Township’s 6,000 3-10 year olds have autistic spectrum disorder. It has made Brick Township the “autism capital of the USA” (but note, East Surrey rates in the UK are higher still). In Brick Township, Federal investigators collected data on surface and ground water, sites of industrial spillages and waste dumping, and also ensured that there had been correct diagnosis of the actual children. They have found nothing untoward. Their findings were reported in April 2000.

 

?         The following is taken from the statistics produced by the Department of Education in the United States, for numbers of children aged 6-21 served by IDEA (Individuals With Disabilities Discrimination Act) who have autism. It compares the increase over the ten years between 1992-93 and 2002-03, including separate figures for 2001-02 to reveal the most recent-year rise that was available when this table was compiled:

 

State

(1991-92)

1992-93

2001-02

2002-03

Alabama

 

68

904

1,096

Alaska

 

8

223

259

Arizona

 

199

1,348

1,689

Arkansas

 

30

774

912

California

 

1,605

13,257

16,093

Colorado

 

14

538

688

Connecticut

 

164

1,470

1,754

Delaware

 

15

294

345

District of Columbia

 

0

144

179

Florida

 

582

4,328

5,117

Georgia

 

262

2,462

3,057

Hawaii

 

52

380

528

Idaho

 

39

356

480

Illinois

 

5

3,802

5,080

Indiana

 

273

3,262

3,975

Iowa

 

67

554

1,148

Kansas

 

74

743

878

Kentucky

 

38

1,022

1,171

Louisiana

 

409

1,297

1,493

Maine

 

37

552

675

Maryland

 

28

2,396

2,692

Massachusetts

 

493

2,681

3,193

Michigan

 

288

4,719

5,463

Minnesota

 

296

3,270

4,116

Mississippi

 

0

461

537

Missouri

 

336

1,953

2,254

Montana

 

20

197

232

Nebraska

 

4

415

481

Nevada

 

5

518

684

New Hampshire

 

0

404

491

New Jersey

 

446

3,526

4,180

New Mexico

 

16

265

311

New York

 

1,648

7,023

8,274

North Carolina

 

786

3,095

3,518

North Dakota

 

9

144

178

Ohio

 

22

3,057

4,017

Oklahoma

 

31

785

829

Oregon

 

37

2,847

3,339

Pennsylvania

 

346

3,969

4,836

Puerto Rico

 

266

518

531

Rhode Island

 

19

384

471

South Carolina

 

141

1,012

1,168

South Dakota

 

36

250

285

Tennessee

 

304

1,103

1,359

Texas

 

1,444

7,099

8,576

Utah

 

105

723

843

Vermont

 

6

248

247

Virginia

 

539

2,365

2,966

Washington

 

476

1,972

2,344

West Virginia

 

101

374

429

Wisconsin

 

18

2,247

2,739

Wyoming

 

15

117

132

Total

5,415

12,222

97,847

118,602

 

(Source: Individuals With Disabilities Education Act data, US Department of Education. Note: Where increases are from a very low base figure, these have been expressed as “almost infinite”.)

 

?         For every single case there was in 1992, by the close of the school year 2002-03 there were 22 cases......

 

?         The 2002 MIND study by Byrd et al (see later) proved that these increases were not ascribable to either better recognition or greater awareness.

 

?         It seems obvious that the US has an autism epidemic. The UK has a very similar health regime to the US, so it also seems reasonable to conclude that the UK probably has an autism epidemic, too, but just hasn’t yet realised it.

 

?         Dr Bernard Rimland of the US Autism Research Institute, San Diego: “Some supposed experts will tell you that the (US) increase reflects only greater awareness. That is nonsense. Any paediatrician, teacher or school official with 20 years experience will confirm there is a real increase, and the numbers are huge and growing”.

 

As in the UK, health officials in the US have tried to explain away these increases as being the result of greater awareness, better recognition and broader diagnostic definition. Doubtless these play some minority part, but the authorities seem to want to use these factors to explain all the increase, without having any hard evidence to support their stance.

 

The criteria changes have been as follows:

 

?              1956, Kanner and Eisenberg propose that just two essential diagnostic features were required to make a diagnosis of autism. These were from areas covering profound lack of affective contact and repetitive ritualistic elaborate behaviour

 

?              In 1978, Rutter proposed that a definition of autism in children required four criteria: (1) impaired social development out of keeping with the child’s intellectual level; (2) impaired language development out of keeping with the child’s intellectual level; (3) stereotyped play patters, abnormal preoccupations and resistance to change; and (4) onset before the age of 30 months.

 

?              In 1980, DSM III (Diagnostic & Statistical Manual of Mental Disorders, third edition) criteria were introduced. Its classification for infantile autism required five criteria (1) lack of responsiveness to others, (2) language absence or abnormalities, (3) resistance to change or attachment to objects, (4) absence of schizophrenic features, and (5) onset before 30 months

 

?              In 1980, the diagnostic criteria for autism were revised once again, to DSM III-R, and a definition of pervasive developmental disorder (PDD) was also introduced.

 

?              Since 1994, the required criteria for autistic disorder has been set out in DSM IV, requiring the meeting of six criteria. Further detailed criteria were also set out for Asperger’s Syndrome (AS) and PDD Not Otherwise Specified (PDD-NOS).

 

?              DSM-IV criteria are more restrictive for autism than hitherto, and when they were introduced, figures for autism in some US States actually fell slightly.

 

The massive increases in US autism are in marked contrast to the moderate increase in other disabilities recorded by IDEA data:

 

 

1991-92

2001-02

% increase

Autism

5,315

97,847

+1,700%

All disabilities (inc autism)

4,499,924

5,853,830

+30%

 

(Source for the above: Autism In The United States: A Perspective, by F. Edward Yazbak, MD, FAAP, Journal of American Physicians and Surgeons, vol 8 no 4 Winter 2003)

 

What this amounts to is that criteria for the mid-1990s onwards became more restrictive. The steep rise in autism witnessed in the US (on the IDEA database) and elsewhere wherever DSM-IV criteria are used (which includes the UK) are thus in the face of this more restrictive eligibility. There is no possibility that increases can be explained away by suggesting that criteria have somehow widened. The increases are real.

 

In April 2000, giving evidence to the Government Reform Committee hearings into autism’s increase, Dr. Coleen Boyle, Associate Director for Science and Public Health at the Center for Disease Control, stated that UK rates in 1966 had been 4 to 5 per 10,000 (1 in 2,500-2,000). Studies from outside the US since 1985 had indicated 12 per 10,000 (1 in 833). Recent studies had been higher still. There had been only two population-based studies in the US, both in the 1980s, indicating prevalence of 1.2 to 3.3 per 10,000 (1 in 8333 to 1 in 3030).

 

Two years on, giving evidence to the same Congressional committee, Dr. Coleen Boyle acknowledged the case of Brick Township New Jersey, where the CDC had found a rate of ASD of 6.7 per 1,000 (note: per ONE thousand), or 1 in 149. She stated that the previously-accepted background rate was 1-2 per 1,000 (comment  -  but this does not square with her evidence in the year-2000 Washington hearings). She stated “We cannot determine whether rates are increasing or not, because we do not have comparable data from earlier years”.

 

But the thrust of her earlier comments implied that, even if increases were demonstrated, this was down to better awareness etc., and at no point did she appear to confront the possibility that increases were real, and then confront the (very troubling) question, “What was causing the increase?”.

 

The CDC strategy seems to be to cast doubt upon the increase, and might be summed up as follows:

 

?             Cast doubt upon the accuracy of the data, and thus draw the focus of debate away from the cause of the increase and towards the data issue

 

?             Stress the need for better data (which no one would argue against)

 

?            Announce new comprehensive data-gathering exercises, which will take more time  -  and thus “buy time”.

 

By early 2003, other evidence that increases were real was also beginning to accumulate  -  see next main section.

 

18.     Autism Elsewhere

 

(Canada)

 

Information on autism in Canada does not appear to be anything like as comprehensive as that in the US, but press reports are indicating a recent increase. In May 2002, a study by the Ontario government health ministry indicated that numbers were increasing sharply, with 800 children younger than six years of age being newly diagnosed during 1998. This represented a 53% increase over numbers diagnosed two years earlier. The Ontario government study also found that 2,863 children younger than seven were diagnosed with autism between 1991 and 1998. The study was not released until the efforts of a parent, Professor Marianna Ofner-Agostini of the University of Toronto, forced the issue.

 

In Canada’s Province of Quebec, the number of children with pervasive developmental disorder (note, this is not full autism) in schools increased by 63% in two years, from 1,388 in September 2001 to 2,267 in September 2003, according to the Ministry of Education. (There is a paper on Quebec in the next section)

 

(New Zealand)

 

The issue is now being debated in developed countries elsewhere in the world. A New Zealand doctor, Dr. Mike Godfrey, wrote to the UK Scotsman newspaper in early 2002 as follows: “I have so far analysed 866 children’s histories, with 260 being unvaccinated. There are no cases of autism, epilepsy or Crohns Disease and only a handful of other diseases in this latter (unvaccinated) group. There are 16 autistics, 12 epileptics, 8 cases of Crohns, plus cases of other illnesses, in the vaccinated 606 children.”

 

(Australia)

 

An early-2004 press report stated that there were 30,000 children in the country with autism, and that there had been a “dramatic increase of more than 200 per cent in diagnoses over the past ten years.” Diagnoses of new cases were reported in 2004 to be running at 17 per week nationally.

 

In 2004, further information was received as follows: “Early in 1997, a TV information item stated a rate of 1 in 600 in Canberra. By mid-1997, diagnoses for the first six months of 1997 had exceeded the number for the whole of 1996, indicating a rate of 1 in 300. In January 2002 (press reports indicated) the rate to be 1 in 100. In the most recent Canberra Autism Association newsletter, 60 diagnoses were reported to have been made in the previous nine months. With 4,617 births in Canberra for year 2002, that represents one diagnosis for every 58 births (Note: this would appear extremely high, but closely matches the Inverness, Scotland, rate of 1 in 49 being quoted in the Scottish press in early 2004).

 

(Denmark)

 

According to a 2004 paper by Dr. Fou Yazbak of the US, the prevalence of autism in children and teenagers under the age of 14 in Denmark, which was 13 per 10,000 in the seven years before MMR was introduced, increased by 542% to 84 per 10,000 in the years 1995-2002 (source: Danish Psychiatric Central Register). The Denmark situation is detailed elsewhere in this Briefing Note.

 

(Finland)

 

There was a striking increase in the incidence of autism recorded in the Northern Provinces between 1991 and 1994, with a cumulative incidence in the 5-7 year age range of 20.7 per 10,000 (1 in 483).

 

(Saudi Arabia)

 

In Saudi Arabia, which has a population of just under 23 million, there were 42,500 confirmed cases of autism in 2002, and many more cases were believed to remain undiagnosed.

 

(Jersey, Channel Islands, UK)

 

Although part of the UK healthcare system, Jersey (a small island off the northern French coast) clearly offers a further insight. There were (as at October 2003) 64 children in Jersey with autism, of which 59 were 16 or under 16. It was reported that a decade earlier, there were only three cases. The under-16 population of the island is 15,664 (2001 census), giving a rate of incidence (discounting undiagnosed cases at the younger end of the age spectrum) of 1 in 265.

 

PART C:    

 

MMR

 

19.     The Introduction Of MMR

 

(some of this information relates to the UK only)

 

Three brands of MMR were introduced into the UK childhood vaccination schedule in October 1988. The vaccines were claimed to be a one-off lifelong protection against the three serious diseases of measles, mumps and rubella. Although it was not made clear at the time, the vaccines’ advantages, according to previous published safety tests, were convenience and economy, rather than greater safety or effectiveness.

 

The vaccine manufacturers were SmithKline Beecham (brand name Pluserix), Merieux (brand name Immravax) and Merck Sharpe Dohme (brand name MMR-II).

 

SmithKline Beecham/Pluserix and Merieux/Immravax both used Schwartz strain measles virus, Urabe AM9 strain mumps virus and Wistar RA27/3 strain rubella virus. Merck Sharpe Dohme/MMR-II used Enders’ Edmonston strain measles virus, Jeryl Lynn strain mumps virus and Wistar RA27/3 strain rubella virus.

 

The UK and US Governments, health authorities and medical establishments behave as though the very concept of vaccine damage does not exist. But it does, and there have been a number of very serious problems with a variety of vaccines, including in recent years, as was recently pointed out by the Congressional Committee on Government Reform in the US:

 

On three occasions in the last fifteen years, changes have been made to vaccine policies to reduce the risk of serious adverse effects. First, a transition from oral polio vaccine to injected polio was accomplished in the US to reduce the transmission of vaccine-induced polio. Second, an acellular pertussis vaccine was developed and a transition from DTP to DTaP was accomplished to reduce the risk of pertussis-induced seizures in children. And when the Rotashield vaccine for rotavirus was linked to a serious bowel condition (intersucception), it was removed from the US market”  -  quote from the report.

 

In the UK, there were to be serious problems with both Pluserix and Immravax versions of MMR. It took the UK Department of Health a full four years to identify these and to withdraw the two brands, in September 1992, due to an emerging link between the Urabe strain mumps virus and aseptic meningitis.

 

The vaccines use an attenuated (weakened) version of the virus to stimulate an immune-system response in the child. In a letter published on 9th February 2002 in The Times (UK), Dr. David Hall, President of the Royal College of Paediatrics and Child Health, stated: “Some children develop encephalitis (brain swelling) when they catch measles, mumps or rubella virus, and may be left with a variety of handicaps, including  physical and mental impairment, deafness, internal organ damage and autism......”

 

So could an insufficiently-attenuated strain of these viruses, administered in the form of a vaccine, also cause autism?

 

20.     Recognised Adverse Reactions to MMR

 

As a background to the controversy about MMR’s safety, it is important to make clear that there is already a range of adverse reactions to the vaccine that are recognised by the manufacturers themselves, if not by the UK Department of Health.

 

The latter insists that the vaccine is safe and has a good safety record worldwide. However, the February 2000 edition of the manufacturer’s notes, issued by Merck & Co., lists the following possible adverse reactions reported during clinical trials:

 

?         (body as a whole) panniculitis, atypical measles, fever, syncope, headache, dizziness, malaise, irritability

 

?         (cardiovascular system) vasculitis

 

?         (digestive system) pancreatitis, diarrhoea, vomiting, parotitis, nausea

 

?         (endocrine system) diabetes mellitus

 

?         (hemic and lymphatic system) thromobocytopenia, purpura, regional lymphadenopathy, leukocytosis

 

?         (immune system) anaphylaxis and anaphylactoid reactions, angioneurotic edema, bronchial spasm

 

?         (musculoskeletal system) arthritis, arthralgia, myalgia

 

?         (nervous system) encephalitis, encephalopathy, measles inclusion body encephalitis (MIBE), subacute sclerosing panencephalitis (SSPE), Guillain-Barre Syndrome, febrile convulsions, afebrile convulsions or seizures, ataxia, polyneuritis, polyneuropathy, ocular palsies, paresthesia. On encephalitis, the Merck notes state that “the data suggest the possibility that some of these (reported) cases may have been caused by measles vaccines.”

 

?         (respiratory system) pneumonitis, sore throat, cough, rhinitis

 

?         (skin) Stevens-Johnson syndrome, erythema multiforme, urticaria, rash, burning/stinging at injection site, wheal and flare, redness, swelling, induration, tenderness, vesiculation at injection site

 

?         (special senses  -  ear) nerve deafness, otitis media

 

?         (special senses  -  eye) retinitis, optic neuritis, papillitis, retrobulbar neuritis, conjunctivitis

 

?         (urogenital system) orchitis

 

?         (other) “death from various and in some cases unknown causes has been reported rarely following vaccination with MMR; however, a causal relationship has not been established”

 

The above, although qualified in Merck’s preamble as being “without regard to causality”, does suggest that rare or relatively rare serious adverse events are not unknown and are already recognised by the manufacturers of MMR. In this context, the possibility of an unrecognised adverse event such as autism  -  particularly if its onset is subtle, insidious and unresearched  -  becomes much more credible.

 

It is also interesting to see that numerous adverse reactions to MMR have actually been reported in the past, as well as adverse reactions (including rare serious reactions) to single vaccines. Although links between adverse events and vaccines are invariably routinely denied by medical and health bodies, it is stretching credibility to suggest that all reported adverse events are unconnected with prior vaccination. The Department of Health’s line seems to be “only good can come from vaccination”. The manufacturers’ own warnings contradict this stance.

 

21.   US Vaccine Adverse Events Reporting System (VAERS)

 

The following statistics are taken from the US VAERS (vaccine adverse events reporting system) database, covering the period from 1st January 1990 to 6th March 2001.

 

The table below also includes some other vaccines, for comparison. It should also be noted that a very small percentage indeed  -  perhaps as low as 1%  -  of adverse events are actually reported to VAERS in practice, and the real numbers will therefore be very much higher. Many of these reactions are extremely minor and transitory, but a considerable number are also very serious, and some reactions are fatalities.

 

(vaccine)

Reported adverse events

Reported serious adverse events

Reported deaths

% of total events reported as serious**

% of adverse events reported as deaths**

Dipther Tet

1,492

189

15

 

 

DTAP

10,348

1,422

283

 

 

DipTetPert

21,163

3,286

794

 

 

DTPH

6,212

928

254

 

 

Flu

15,351

2,082

324

 

 

Hepatitus B

32,209

4,676

662

 

 

HibV

21,726

3,905

932

 

 

Measles

414

61

7

15%

2%

Measles M

34

25

2

74%

6%

MMR

20,974

2,586

132

12%

1%

Measles R

117

23

0

20%

0%

Mumps

54

19

3

35%

6%

Polio live or

24,702

3,541

970

 

 

Pneumococ

5,841

712

95

 

 

Rubella

685

100

1

15%

0%

Tetanus Dip

9,566

520

12

 

 

Varicella

12,635

590

31

 

 

TOTALS*

201,815

27,768

4,965

14%

2%

 

Notes: * totals include a number of other vaccines, not included in the table,

** percentages only calculated selectively for components of MMR. Full titles of those vaccines itemised in the table are (1) dipitheria tetanus, (2) diptheria tetanus acellular pertussis, (3) diptheria pertussis tetanus, (4) diptheria pertussis tetanus haemophilus B, (5) influenza, (6) hepatitus B, (7) haemophilus B, (8) measles virus live, (9) measles mumps virus live, (10) measles mumps rubella virus live, (11) measles rubella virus live, (12) mumps, (13) poliovirus live oral, (14) pneumococcal, (15) rubella virus live, (16) tetanus diptheria adult, (17) varicella.

 

It is noteworthy that MMR and the various other components of vaccines for measles, mumps and rubella appear to account for 2,814 reported serious adverse events and 145 deaths. This has to be set against the many millions of doses administered, but also against the likely levels of under-reporting. For the autism issue, under-reporting is likely to be very high indeed, perhaps even almost total, due to lack of knowledge on the part of both parents and health professionals.

 

More up-to-date information has been obtained in relation to years 1999-2002, covering adverse reactions, hospitalizations and deaths data on the US Vaccine Adverse Events Reporting System database:

 

(adverse reactions reported to VAERS 1999-2002 ages 0-6 years):

 

(vaccine)

(number of adverse events reported)

DTaP

16,544

Flu

419

HepB

13,363

Hib

22,463

MMR

18,680

OPV

22,915

Varc

11,246 (from 1995)

 

(hospitalizations reported to VAERS 1999-2002 ages 0-6 years)

 

(vaccine)

(number of adverse events reported)

DTaP

1,631

Flu

41

HepB

1,840

Hib

3,224

MMR

1,736

OPV

2,868

Varc

576 (from 1995)

 

(deaths reported to VAERS 1999-2002 ages 0-6 years)

 

(vaccine)

(number of adverse events reported)

DTaP

394 deaths

Flu

11 deaths

HepB

642 deaths

Hib

843 deaths

MMR

110 deaths

OPV

866 deaths

Varc

34 deaths (from 1995)

 

It is interesting to note that 20,526 adverse events were reported 1999-2002 for MMR, including 110 deaths. The VAERS data is regarded as a gross underestimate of the true number of adverse events.

 

22.     Contraindications to Receiving MMR

 

This list of potential contraindications to receiving MMR, contained in the Merck manufacturer’s information sheets, is also lengthy. It is very questionable as to whether all parents of UK recipients of MMR during the late 1980s and the 1990s were questioned in detail by their healthcare professionals on these aspects before their child received MMR.

 

Department of Health leaflets are extremely uninformative about both adverse reactions and contraindications, barely mentioning them. The moral pressure is always to press ahead with giving the child MMR, and indeed, doctors receive a significant financial bonus for achieving takeup targets. The bonus is not on a pro-rata sliding scale  -  if you are just short of the target, you receive a nil bonus. The pressure is therefore considerable, particularly where takeup rates hover just around the target threshold.

 

Contraindications recognised by the manufacturers (but in almost all cases not passed on to the public by the Department of Health) include:

 

?         Hypersensitivity to any component of MMR, including gelatine

 

?         Anaphylactic or anaphylactoid reactions to neomycin

 

?         Febrile respiratory illness or other active febrile infection

 

?         Patients receiving immunosuppressive therapy

 

?         Individuals with blood dyscrasias, leukemia, lymphomas of any type or other malignant neoplasms affecting the bone marrow or lymphatic system

 

?         Primary and acquired immunodeficiency states, including patients who are immunosuppressed in association with AIDS or other clinical manifestations of infection with human immunodeficiency viruses

 

?         Patients with cellular immune deficiencies or hypogammaglobulinemic and dysgammaglobulinemic states. The Merck information sheets note that “Measles inclusion body encephalitis (MIBE), pneumonitis and death as a direct consequence of disseminated measles vaccine virus infection has been reported in immunocompromised individuals inadvertently vaccinated with measles-containing vaccine”

 

?         Individuals with a family history of congenital or hereditary immunodeficiency, until the immune competence of the potential vaccine recipient is demonstrated

 

Some of the above contraindications could be partly relevant to the MMR/autism issue. And clearly, if a hitherto-unrecognised syndrome such as the insidious onset of autism, should exist but go unreported, then the list of contraindications would remain too narrowly defined until the syndrome became recognised. Much therefore depends on the effectiveness of reporting systems and length of follow-up. These issues will be covered later.

 

23.      The UK Department of Health’s Position On MMR And Autism

 

?         Despite research pointing to an original failure to properly conduct safety tests with adequate follow-up of MMR (see later), and emerging research linking MMR with autism (autistic enterocolitis syndrome) and/or inflammatory bowel disease, the UK Department of Health and other medical institutions continue to insist that MMR is safe.

?         This claim is based upon advice of the UK Committee on Safety of Medicines and Joint Committee on Vaccination and Immunisation  -  both of which would suffer a catastrophic loss of public confidence, should such a link emerge  -  and a number of studies, all of which arguably have severe methodological weaknesses or inconclusive outcomes. Details follow later in the text.

 ?         Much of the support for MMR, and denial of a link with autism, is based around a very small number of these studies, which the various sectors of the medical establishment have then endorsed.

 ?         There have also been general reviews of the MMR/autism issue by the Medical Research Council, most recently in late 2001, and by other bodies. These reviews have failed to find a link between MMR & autism. The parents believe this failure was inevitable, given the past lack of funded research into causes, and the superficial nature of these reviews, which have accepted “absence of evidence” as “evidence of absence” of a link.

 ?         The outcome of these reviews, and other published papers, has then been misrepresented or misinterpreted by the Department of Health as hard evidence that there is not a link.

 ?         The DoH-sponsored impression of “a growing body of evidence” that there is no MMR/autism link is therefore illusory  -  the “house of cards”.

 

?         The situation mirrors that in the US, where there is official Congressional recognition of it:

 

“To date, studies conducted or funded by the CDC (US Centers for Disease Control) that purportedly dispute any correlation between autism and vaccine injury have been of poor design, under-powered and fatally flawed. The CDC’s rush to support and promote such research is reflective of a philosophical conflict in looking fairly at emerging theories and clinical data related to adverse reactions from vaccinations”  -  quote from the conclusions of a report of the Subcommittee on Human Rights and Wellness, Committee on Government Reform, US House of Representatives, May 2003

 

?         The UK Department of Health’s position on MMR has been endorsed by many of the major medical institutions, though it is questionable whether these institutions have themselves fully considered, in adequate detail, all the evidence on both sides of the argument.

 ?         It is also unlikely that any of these bodies has met with parents or listened sufficiently attentively (or even at all) to their accounts of how their children degenerated. It is likely that some of the bodies, and spokespersons, backing MMR and refuting a link with autism are entirely basing their confidence upon a few selected studies, and that their knowledge of the actual children believed to have been damaged is very poor. Their detailed knowledge of the studies that point towards there being a problem may be weak and incomplete.

 ?         The starting point should be to “listen to the patient”. Most of those giving reassurance have never even met the patient, nor the patient’s parents, nor examined the affected child, nor reviewed their medical case-notes.

 

24.     Single Vaccines In The UK

 ?         Despite the DoH’s position of “MMR or nothing” (and increasing numbers of parents seem to be choosing the latter), when MMR was introduced in 1988,  the UK National Health Service advice to doctors was that single vaccines should be made available for any parents not wishing their child to have MMR.

 ?         In the pamphlet, Immunisation Against Infectious Disease”, which accompanied the introduction of MMR to the UK, it stated: “For children whose parents refuse MMR vaccine, single antigen measles vaccine will be available” (source: Joint Committee on Vaccination and Immunisation, 1988). It is unclear when, or why, this advice was withdrawn by the DoH, but it may have followed discontinuation of the single vaccines as an economy measure. In the 1996 edition it states, page 135, 22.2.3, “single antigen measles mumps and rubella vaccines are available”, so perhaps it was dropped some time after this date as stocks of single vaccines were reduced.

 

25.     Measles In The UK

 ?         There have also been numerous spurious claims about measles deaths, aimed at frightening parents into having MMR. For example, the Chief Medical Officer for England, Professor Sir Liam Donaldson, told the BBC Today programme that Dr. Andrew Wakefield’s research had led to a loss of confidence in MMR, a vaccine “that had saved millions of children’s lives”. The implication was that a large proportion of these “saved” lives was in the UK.

?         The truth was very different. Dr. F. Edward Yazbak, in a letter to the British Medical Journal in March 2004, pointed out that UK measles deaths had decreased precipitously before the introduction of measles vaccines, because of better nutrition and hygiene. “The following can be checked with the (UK) Department of Health. In 1901 there were 9,019 deaths attributed to measles, in a population of 32,612,000 in England and Wales, giving a mortality of 276.5 per million. In 1960 (before measles vaccination was introduced, using the single vaccine), there were 80 deaths and the total population was 45,775,000.

?         The measles mortality rate in England and Wales was therefore 1.75 per million in 1960. In other words, the mortality rate from measles had decreased by 99.12% before the introduction of the (single) measles vaccine.”

?         It is also interesting to note that, bearing in mind that health officials routinely wave-away claims of potential damage from vaccines as being a “one in a million” chance, but that even as long ago as 1960, the actual recorded death rate from measles was barely much more than the proverbial “one in a million”.

 

26.     Promotion Of MMR In The UK After The Wakefield “Early Report” Controversy

 

?         During the years 1998-2004, a one-sided view of the MMR/autism issue has thus been adopted by the Department of Health and its satellite organisations, much of it aimed at restoring public confidence in immunisation, to fight communicable diseases, rather than rigorously searching-out the cause of the damage to the actual children. Fresh publicity issued during early 2002 took a one-sided view of the debate, and ignored some key scientific evidence such as the January 2002 research by Dr. Vijendra Singh (see later), despite the latter being widely available in advance of the date of the Department’s publicity.

 ?         A similar denial process has occurred in the US, but its main roots lie in the UK, and based on (mainly statistical) advice stemming from only a very small number of sources.

 ?         At the end of 2001, the UK Department of Health released a “Top 10 Truths/Top 10 Myths” leaflet about MMR, and this is summarised below, with a critique alongside:

 

(UK Department of Health’s “Top 10 Truths”)

 

(Department of Health “Truth”)

(Critical Response of Parents)

MMR is safest way to protect children

Does not address the alleged damage

Over 500m doses of MMR have been used in over 90 countries

Almost all those countries have no autism database. Only US has good data  -  and this shows a steep rise in autism

No country in the world recommends single vaccines

No country in the world has yet acknowledged that there may be an MMR/autism link, either, but that may yet follow in time. Some countries permit single vaccines as a choice.

Children who are not immunised with MMR increase the chance of infection in others.

True. But those children could still receive single vaccines. And there may yet be a massive loss of confidence in all vaccination, if the children win in the High Court. It would therefore be prudent to think of this possibility, and permit choice now.

The evidence is that MMR does not cause autism or IBD (a number of studies are quoted, but only those which suit the Department’s stance)

There is evidence that suggests that it may do. Every one of the quoted studies that “disproves” an MMR/autism link can be flawed (see elsewhere in this document).

Wakefield et al in 1998 said “We did not prove an association”.

True. The research is still unfolding. Time did not stop in 1998.

Single vaccines put children at risk

The Department’s argument is based upon a supposition that some children would not complete the full course of vaccines. But if the children win in the High Court, and the Department is shown to have misled the public (either unknowingly or knowingly), the damage will be far greater. And already, some children are avoiding any measles vaccine. The Department’s argument is already having a perverse consequence, and may eventually massively backfire..

MMR was thoroughly tested before introduction into the UK in 1988.

In the context of adverse outcomes with an insidious long-term onset, MMR was not properly tested. Advice at the time to explore possible adverse effects was not followed up. By disputing historical facts, the Department reveals its bias.

Two doses of MMR are needed to protect children.

The efficacy of MMR in terms of preventing measles is not the point at issue.

There are very few children with genuine contraindications.

This does not address the MMR/autism link. It also does not square with the manufacturer’s own information sheets, which imply a substantial number of possible adverse effects.

 

The Department of Health’s “Top 10 Truths” leaflet ends with the reassuring statement, “All of the above are correct”! The above critique suggests that the “truth” is nowhere near clear-cut, and the Department’s position is thus exposed as artificial and one-sided.

 

(UK Department of Health’s “Top 10 Myths”)

 

(Department of Health “Myth”)

(Critical Response of Parents)

Getting protection by catching the disease is better.

This is not the issue in dispute.

Three viruses given at the same time is too much for children.

It may yet prove to be. The Department has no evidence (in the context of the MMR/autism debate) to the contrary, in relation to live viruses.

Other countries recommend that MMR is given as separate vaccines.

Of course they don’t. Perhaps this is because no country has yet woken up to the problem. As yet, there is insufficient evidence to alter this position.

Measles, mumps and rubella are rare in the UK so there is no need to immunise.

This is not the issue in dispute.

MMR causes autism and bowel disease.

There is evidence pointing towards an MMR/autism/IBD connection. Until this area is thoroughly researched, it is scientifically untenable to rule it out.

There was a scientific paper that linked MMR and autism/IBD

There have now been a number of such papers. They form part of an unfolding story.

Giving MMR as separate vaccines reduces the risk of side effects.

It is not possible to prove/disprove this until proper clinical research has been funded and conducted.

The vaccine was not properly tested.

In the context of the MMR/autism debate, and the alleged link, this is factually true, and it is extraordinary for the Department to claim otherwise. Even the Department cannot re-write history.

My child has already received one dose, so does not need a second dose.

This is not the issue in dispute.

My son does not need protection against rubella, my daughter does not need protection against mumps.

This is not the issue in dispute.

 

The Department of Health’s leaflet ends, “All of the above are wrong”. In the view of the parents, of the “Top 10 Myths”, four are irrelevant to the debate about an MMR/autism link, one statement about a “Myth” is factually incorrect, and the remainder can readily be disputed because the research has not been completed, or in some cases even commissioned, to decide the issue either way.

 

The position in the US is no different. In summer 2002, the US Center for Disease Control (CDC) updated its “Frequently Asked Questions” (FAQs) on the MMR/autism issue. It asked the question: “What have studies found regarding MMR vaccine and autism?”.

 

Its answer was “Epidemiologic studies have shown no relationship between MMR vaccination in children and development of autism”. However, what it did not acknowledge, or discuss, was that “studies” in the original question should have included both clinical and epidemiological studies, with greatest weight being attached to clinical findings. Its answer ducked the issue of clinical studies, focussing solely on epidemiological studies (see later for a critical review of these).

 

The Department’s position on measles as a disease is also open to question. The Chief Medical Officer for England, Professor Sir Liam Donaldson, claimed during a BBC Radio 4 Today Programme interview that DR. Wakefield’s research had led to a loss of confidence in a vaccine that had claimed “millions” of children’s lives. But in a written response, Dr. F. Edward Yazbak has pointed out that measles deaths in the UK had declined precipitously before the introduction of the measles vaccine, because of better nutrition and improvements in hygiene.

 

According to the Department of Health’s own figures, in 1901 there were 9,019 deaths attributed to measles in England and Wales, amongst a total population including adults) of 32.6m, giving a mortality rate of 276.5 per million. In 1960, there were 80 deaths amongst a population of 45.8m, giving a mortality of 1.75 per million. In other words, mortality attributed to measles had declined by over 99% before the introduction of measles vaccine.

 

27.     Position of US Center for Disease Control on MMR/Autism

 

The position of the US Center for Disease Control is summarised as follows (taken from their website in February 2002, but believed to be unchanged as at 2004):

 ?              Is there any scientific evidence that provides a link between autism and vaccination?  -  To date there is no convincing evidence that any vaccine can cause autism or any kind of behavioural disorder. A suspected link between MMR vaccine and autism has been suggested (but this).......may simply be an.....unrelated chance occurrence.

 ?              Is there a theoretical possibility that there is a connection between autism and MMR vaccine, or any other vaccine?  -  If measles vaccine or any other vaccine causes autism, then it would have to be a very rare occurrence, since millions of children have received vaccines without ill effects.

 ?              What are the known side-effects associated with MMR?  -  About 5-15% of vaccinees may develop a fever 5-12 days after MMR, and 5% may develop a rash (comment  -  not clear if this means 5% within the 15% or 5% plus the 15%). Central nervous system conditions, including encephalitis and encephalopathy, have been reported with a frequency of less than one per million doses administered

 ?              What is the federal government doing to protect the health of persons who receive MMR?  -  There are no proven data to suggest that measles vaccine will increase the risk of developing autism or other behavioural disorders.

 

Comment:  the above is neither comprehensive nor balanced, and its one-sided reassurance is therefore unhelpful. The details of the above could even be challenged on the grounds of factual accuracy. Point one is particularly threadbare.

 

The position of the US health authorities on thimerosal is equally evasive. There is no admission of potential harm. The thimerosal issue is covered elsewhere in this Briefing Note.

 

28:     The Parents Have Seen What They’ve Seen.......

 

It is not in dispute that vaccines have saved millions of lives. The MMR/autism parents are not anti-vaccination in principle. These parents all took children to be vaccinated. We all recognise the need to protect children from diseases.

 

But saving lives from diseases doesn’t justify ruining significant numbers of lives from unrecognised and unmonitored vaccine damage.

 

It is also felt by many parents that the mantra “the benefits of vaccination outweigh the risks” has become increasingly skewed by

 

?         (a) occasionally overstating the dangers of diseases, citing experience of diseases from poor and underdeveloped countries, or UK experiences from half a century ago, or pointing to recent deaths (e.g. Ireland) where other factors played a major part, or

 ?         (b) grossly underplaying or dismissing outright any risks from vaccination. This latter has been aided by the extremely poor monitoring of adverse outcomes, and by the authorities strenuously refusing to accept that an adverse outcome was the result of a vaccine.

 

All affected parents are in the privileged position of having watched their child degenerate. It is a powerful first-hand experience. Comparing notes results in finding that other parents have undergone extremely similar experiences. Unfortunately, such experiences are not part of a scientifically-controlled study, so are routinely dismissed by the Department of Health as anecdotal.

 

?         Usually there appears to be a very gradual degeneration over many weeks and months, not an acute event, more akin to (eg) the onset of cancer than the rare acute reactions to vaccines seen in the past.

 ?         But all the attention of the past upon possible adverse reactions to vaccines has focussed upon acute near-immediate events.

 ?         The onset of gut/bowel problems and hyperactivity have accompanied the onset of autism. Some link between them is therefore likely, even without detailed research.

 ?         An anecdote is an anecdote. A consistent pattern of anecdotes is much more powerful. What we have is a consistent detailed pattern of reports from parents. The importance of this pattern has been ignored by the Department of Health.

 

The view of affected parents can be summed up by two quotes from Canada:

 

Basically, I haven’t met a single person with autism who can’t trace it to the shots. Our stories are all the same. My kid had the DPT and he started getting sick. He had the MMR and we thought he went deaf. We gave him antibiotics for an ear infection.....and suddenly he’s going spinning and twirling and laughing for no reason. You’d have to be an idiot not to see the connection.” (Cynthia Stark, Canadian parent)

 

How is it possible that (the medical establishment) can ignore it? They keep talking about environmental factors. What is this mysterious environmental factor? I hear the same stories over and over again. A few months after an MMR shot, a child begins to regress and to lose milestones. That’s the repeated “broken record” that keeps being told over and over. I see the MMR as the straw that breaks the child’s health.” (Edda West, of the Vaccine Risk Awareness Network, Canada)

 

PART D

 

THE THIMEROSAL/THIOMERSAL ISSUE

 

29.   Thiomersal’s Possible Role

 

This section commences with some quotes:

 

My grandson received vaccines for nine different diseases in one day. He might have been exposed to 62.5 micrograms of mercury in one day through his (US Food and Drug Administration-approved) vaccines. According to his weight, the maximum safe level that he should be exposed to in one day (according to the US Environmental Protection Agency) is 1.51 micrograms. This is (therefore) 41 times the amount at which harm can be caused”  -  letter from Rep. Dan Burton, then Chairman of the House of Representatives’ Committee on Government Reform, to the then US Department of Health and Human Services Secretary Donna Shalala, October 2000

 

and.....

 

In 2001, the Institute of Medicine stated that it is “unclear whether ethylmercury (from vaccines) passes readily through the blood-brain barrier. Th IoM recommended several biological and clinical studies to answer this question.....These studies were in a large part never done.....Even today, the IoM cannot tell you with any degree of certainty what happens to ethylmercury once injected into an infant. Does it go to the brain? Does it cause developmental problems?”  -  Press Release by Representative David Weldon, US House of Representatives, May 2004

 

and.....

 

In 2003, the staff of Rep. Dan Burton, member of the US House of Representatives for Indiana, obtained a confidential internal US Government email written in June 1999 by former Food and Drug Administration scientist Peter Patriarca, offering an assessment  of the impending statement in July 1999 by the US Public Health Service urging manufacturers of vaccines to reduce or eliminate thimerosal: “(This) will raise questions about the FDA being asleep at the switch for decades, by allowing a potentially hazardous compound to remain in many childhood vaccines, and not forcing manufacturers to exclude it from new products. Will also raise questions about various advisory bodies about aggressive recommendations for use.  We must keep in mind that the dose of ethylmercury was not generated by rocket science  -  conversion of the percentage of thimerosal to actual (micrograms) of mercury involves 9th grade algebra. What took the FDA so long to do the calculations? Why didn’t the Centers for Disease Control and the advisory bodies do these calculations while rapidly expanding the childhood immunisation schedule?”

 

The currently-stalled UK litigation regarding autism and vaccination were proceeding on the basis of autism following MMR (or MR) vaccination. In contrast, in the US, cases are taking legal action over the link between autism and thiomersal, the mercury-based preservative used in many vaccines for several decades, both in the UK and US.

 

It is understood that thiomersal, a mercury-based preservative, has been used in a number of UK and US vaccines over many years. It is believed that it is not used in MMR itself, but it may yet prove to have been used in the manufacturing process. If this is the case, it is believed that no declaration has to be made on the manufacturer’s information sheet, as it is not an actual MMR constituent.

 

In the US, in the 70 years since thimerosal/thiomersal/merthiolate preservative was developed, the Food and Drug Administration never required manufacturers Eli Lilly to conduct clinical studies of its safety. Even in 2004, the FDA still referred to the original 1931 Powell and Jamieson study (which offered no proof of thimerosal’s safety) as an indication of its “safety and effectiveness as a preservative.

 

Eli Lilly ceased manufacture of thimerosal-containing products in the mid-1980s, but thimerosal remained in widespread common use, including in vaccines, into the 21st century. Eli Lilly still has revenue from licensing agreements with other pharmaceuticals companies using thimerosal all around the world.

 

The key point about thimerosal is that no-one thought to check that, as more and more vaccines were recommended for infants, whether this produced a cumulative total that was in excess of safety guidelines.

 

The two suspected causes, MMR and thimerosal, are not mutually exclusive. It has never been suggested that MMR causes all autism, and the two factors may in any case be working in concert.

 

?         The thimerosal issue emerged when the 1997 US Food & Drugs Administration Bill was passed, a re-authorisation bill that required the FDA to compile a list of drugs and foods that contained intentionally-introduced mercury compounds. In June 1999, the FDA issued a report indicating that “infants who receive thimerosal-containing vaccines at several visits may be exposed to more mercury than recommended by Federal guidelines for total mercury exposure”.

 ?         Despite the FDA’s report, there was no ordered recall of the vaccines. However, the FDA asked the manufacturers to reduce the mercury content, and they complied.

 ?         Worldwide, thimerosal has been used for about the past 60 years. Ethyl mercury constitutes about 49.6% of its weight, and mediates the antimicrobial effects. Thimerosal has been used to prevent bacterial contamination during the vaccine manufacturing process, as well as in vials where repeated puncture may allow contamination to occur.

 ?         It is believed that levels of thimerosal have been reduced over the years in vaccines, and removed altogether in some cases. In April 2001, the US Food & Drug Administration announced that they supported the reduction of mercury exposure from any source. The FDA then encouraged vaccine manufacturers to develop new vaccines without thimerosal. In the US, in 2001, a free exchange system was instigated by the manufacturers, to remove stocks.

 ?         In the UK, the Department of Health has refused to acknowledge that there might be a problem with thimerosal, and no free exchange system has been offered, or sought. Thimerosal continues in use in a number of vaccines, not just those for children. As recently as January 2003, press reports in The Scotsman newspaper indicated that four out of the seven influenza vaccines in use in the UK contained thimerosal, and this was not refuted by the Department of Health.

 ?         In the US, a September 2001 survey of 65,909 vaccines at provider centres found that 5.5% still contained thimerosal. Some 36% of these were DtaP-Hib for the fourth dose. A depot survey of 837,174 vaccine doses found that 1% still contained thimerosal. Of these, 80% were for DtaP.

 ?              In early 2003, calls for all thimerosal to be removed from vaccine use were renewed. Michael Bender, Director of the Mercury Policy Project, stated that continued use was irresponsible and not worth the risk. Sallie Bernard, Director of the Safe Minds charity, said that there was no “safe” level for mercury in vaccines, and that use should cease unequivocally and without delay. Barbara Loe Fisher, President of the National Vaccine Information Center, said that all vaccines should be mercury-free.

 

30.   Joint Statement of American Academy of Pediatrics and Public Health Service, Thiomersal In Vaccines, July 1999

 

In 1999, researchers calculated that a low-birthweight baby could receive a cumulative dose of mercury (187ug) that would have exceeded the safety recommendations of the US Environmental Protection Agency.

 

In July 1999 the AAP and the PHS issued a joint statement on thimerosal in vaccines, noting that the US Food & Drug Administration Modernization Act of 1997 called for the FDA to review and assess the risk of all mercury-containing food and drugs.

 

The joint statement was generous in its self-reassurance:

 

?         Thiomersal has been used as an additive......since the 1930s......”

 ?         There is a significant safety margin incorporated into all the acceptable mercury exposure limits

 ?         There are no data or evidence of any harm caused by the level of exposure that some children may have encountered” (Comment  -  but this may reflect lack of studies or lack of monitoring, not lack of harm)

 ?         Infants and children who have received thiomersal-containing vaccines do not need to be tested for mercury exposure” (Comment  -  as an example of complacency, this statement is in a class of its own).

 ?         The recognition that some children could be exposed to a cumulative level of mercury over the first six months of life that exceeds one of the federal guidelines on methyl mercury now requires a weighing of two different types of risk.....The large risks of not vaccinating children far outweigh the unknown and probably much smaller risk, if any, of cumulative exposure to thiomersal-containing vaccines” (Comment  -  this is an tautological statement, and is revealing. What the AAP/PHS are saying is, the risks from thiomersal are unknown, are probably small, and are far outweighed by another risk  -  which of course is an impossible deduction to draw if the risks from thiomersal are unknown. One cannot say for certain that A is larger than B if there is no way of determining the size of B, or if the size of B is unknown because it has been historically overlooked, and thus not measured).

 ?         Nevertheless, because any potential risk is of concern, the PHS, the AAP and the vaccine manufacturers agree that thiomersal-containing vaccines should be removed as soon as possible”.

 Key action agreed was:

 ?         A formal request to manufacturers for a clear commitment and a plan to eliminate or reduce mercury content of vaccines

 ?         A review of data

 ?         Expedited FDA review of manufacturers’ supplements to their product license applications, to eliminate or reduce mercury content

 ?         Studies to better-understand the risks and benefits of this safety assessment

 

31.     Removal of Thimerosal

 

The following is quoted from a paper, Vaccination  -  An Analysis of the Health Risks, Part 1, by Gary Null PhD and Martin Feldman MD: published in Townsend Letter for Doctors & Patients, October 2003

 

“Use of thimerosal  -  In July 1999, the American Academy of Pediatrics issued a statement urging the removal of the mercury-containing preservative thimerosal from vaccines. The Centers for Disease Control and Prevention (reported) that as of April 2001, all seven of the vaccines recommended for use in all children contain either no thimerosal or trace elements only. These vaccines include Hepatitis B, Haemophilus influenza B, and DTaP (Diphtheria tetanus acellular Pertussis) which formerly contained thimerosal as a preservative, and MMR, polio, varicella and pneumococcal (which have never contained thimerosal).

 

The FDA explained that the vaccines were now being produced as either thimerosal-free or thimerosal-reduced products. The term “thimerosal-reduced” indicated that trace amounts of mercury  -  less than 0.5mcg per 0.5ml vaccine dose  -  may remain from the use of thimerosal in the manufacturing process, but that thimerosal was no longer added as a preservative. The term “thimerosal-free” means that a vaccine does not have a preservative but, again, that trace amounts may remain from the manufacturing process”.

 

What this report did not make clear, as is explained later in the papers by Geier and Geier, was that large stocks of thimerosal-containing vaccines, some with expiry dates of 2005, remained in use, and were not recalled, but were being used up in children.

 

32.   Waters & Kraus Press Release of March 17th 2002

 

In March 2002, the lawyers Waters and Kraus, acting on behalf of US children in the thiomersal/autism class action, stated that their discovery process in their case of Counter v. Eli Lilly (manufacturers of thiomersal) had demonstrated that thiomersal was known by Lilly as early as April 1930 to be dangerous. These included the following studies/warnings deposited with Lilly:

 

?         (1947) “It may be dangerous to inject a serum containing merthiolate into a patient sensitive to merthiolate”

 ?         (1963) “It seems advisable to use a preservative other than merthiolate for injections into merthiolate-sensitive people”

 ?         (1972) Merthiolate in vaccines caused six deaths  -  “The symptoms and clinical course of the six patients suggest subacute mercury poisoning”

 ?         (1982) The (FDA) Panel concludes that thimerosal is not safe for OTC topical use because of its potential for cell damage if applied to broken skin, and its allergy potential”.

?         (1991) Lilly ceases manufacture or sale of thimerosal. Licensing agreements demonstrate continued profits from the product until at least 2010

?         (1999) Lilly advice on thimerosal: “Mercury poisoning may occurr.....Exposure in children may cause mild to severe mental retardation”.

 

In July 2002, the Indianapolis Star newspaper quoted the lawyers Waters and Kraus as saying that “Lilly flim-flammed scientists for years with a 1931 study that concluded thiomersal wasn’t harmful to humans”. The Star went on: “The study, published in the American Journal of Hygiene, reported that merthiolate has a very low order of toxicity......for man”.

 

Digging further, Waters found out that the study’s toxicity data came from experimental use of thimerosal by doctors from Lilly and Indianapolis City Hospital on meningitis patients during a severe outbreak in 1929-30. ‘The 1931 study on a cohort of severely ill people (who all died) ended up being quoted in Lilly brochures into the 1980s’, Waters said. ‘It very clearly demonstrates an effort to do an unethical study and then paint the results in a certain way that helps them sell this product’. Lilly ignored or covered up later evidence that thimerosal, which contains 50 per cent mercury by weight, can be dangerous to humans”, Waters said.

 

The detailed sequence uncovered by Waters (the wording is taken directly from their press release) is as follows:

 

?              September 1930, Lilly secretly sponsor a “human toxicity” study on patients dying of meningococcal meningitis. Waters then states: “Lilly then cited this study repeatedly as proof that thimerosal was of low toxicity and harmless to humans. They never revealed to the scientific community or the public the highly questionable nature of the original research.”

 ?              Numerous articles since the 1930s indicated concerns about thiomersal and its potential hazard to humans. The evidence clearly demonstrates (according to Waters & Kraus) that Eli Lilly was advised repeatedly that their conclusions on low toxicity were not warranted, and they failed to pass the information on to appropriate Federal and public health authorities.

 ?              1947, article received by Lilly states: “No eruptions or reactions have been observed or reported to merthiolate internally, but it may be dangerous to inject a serum containing merthiolate into a patient sensitive to merthiolate”

 ?              1948, article received by Lilly, “Merthiolate is such a commonly-used preservative for biologicals, plasma, cartilage etc. that it would seem important to determine whether harm would result following its subcutaneous or intravenous injection in skin-sensitive individuals.”

 ?              1950, New York Academy of Science article, “Mercurials as Antiseptics”, states “It (merthiolate) is toxic when injected parenterally and therefore cannot be used in chemotherapy”

 ?              1963, article received by Lilly, “There is another point of practical significance: does the parenteral injection of merthiolate-containing fluids cause disturbance in merthiolate-sensitive patients?” “It is known that persons that are contact-sensitive to a drug may tolerate the same medications internally, but it seems advisable to use a preservative other than merthiolate for injections in merthiolate-sensitive people”

 ?              17/8/1967, Medical/Science department requests that the claim “non-toxic” on thiomersal labels be deleted in next printing run

 ?              29/8/67, draft label changed to “non-irritating to body tissues”, non-toxic wording omitted

 ?              1972, British Medical Journal reports case of skin burns resulting from the chemical interaction of thimerosal and aluminium. “Mercury is known to act as a catalyst and to cause aluminium to oxidize rapidly, with the production of heat”. “The manufacturers who supply us with thimerosal have been informed” (thiomersal is being used in vaccines which also contain aluminium).

 ?              1972, article received by Lilly: “Merthiolate in vaccines caused six deaths? The symptoms and clinical course of the six patients suggest subacute mercury poisoning”

 ?              27/4/76, Lilly responds to Rexal Drug Company’s efforts to place the following warning on merthiolate product: “Frequent or prolonged use or application to large areas may cause mercury poisoning”  -  Lilly objects to this proposed warning, stating: “We object to the connection of our trademark with the unjustified alarm and concern on the part of the user which the statement is likely to cause. We are not aware of any instance of ‘mercury poisoning’ after decades of marketing this product. This is because the mercury in the product is organically bound ethylmercury as a completely non-toxic nature, not ethylmercury.” (Comment: this wording does not make complete sense?)

 ?              5/1/1982, Food & Drug Administration’s advance notice of proposed rule-making regarding thiomersal: “At the cellular level, thimerosal has been found to be more toxic for human epithelial cells in vitro than mercuric chloride, mercuric nitrate, and merbromim (mercurichrom). It was found to be 35.3 times more toxic for embryonic chick heart tissue than for staphylococcus areas”. A 1950 study showed that thiomersal was no better than water in protecting mice from potential fatal streptococcal infection. The panel concludes that thimerosal is not safe for over-the-counter topical use because of its potential for cell damage if applied to broken skin, and its allergy potential. It is not effective as a topical antimicrobial because its bacteriastatic action can be reversed.”

 ?              7/4/1983, additional language added to some Lilly labels: “As with any drug, if you are pregnant or nursing a baby, seek the advice of a health professional before using this product”

 ?              1991, Lilly ceases manufacture/sale of thimerosal. Licensing agreements demonstrate continued profits from the product until at least 2010

 ?              8/12/99, Lilly notes include: “Primary physical and reproduction effects. Nervous system and reproduction effects. Effects of exposure include fetal changes. Mercury poisoning may occur. Exposure in children may cause mild to severe mental retardation. Hypersensitivity to mercury is a medical condition, aggravated by exposure”

 

The next pivotal event was the year-2000 Simpsonwood review by the US Centers For Disease Control. A detailed account of this event is set out later, in the section covering evidence for a thimerosal/autism link (note the “for”).

 

33.     United States Use of Thimerosal  -  Statement to the Institute of Medicine by Dr. Mark Geier, February 9th 2004

 

As part of his submission on links between thimerosal and neurodevelopmental disorders, Dr. Mark Geier and David Geier provided the following useful profile of US thimerosal use:

 

?              It is clear that, despite public perception that thimerosal has been removed from all US vaccines, it is obvious that thimerosal continues to be present in a number of vaccines at non-trace concentrations

?              Additionally, the removal of thimerosal from the routinely recommended childhood immunisation schedule took considerably longer than is commonly acknowledged

?              On July 17th 2003, the Associate Commissioner for Legislation for the FDA wrote a response letter to a March 12th 2003 letter written by Congressman Weldon inquiring about the presence of thimerosal in vaccines

?              This response states that the routinely recommended pediatric vaccines (those recommended by  the Advisory Committee on Immunisation Practices, the US equivalent of the UK’s Joint Committee on Vaccination and Immunisation) that are administered during the first two years of life (hep B vaccine, inactivated polio vaccine, the 7-valent pneumococcal conjugate vaccine, the Hib vaccine, DTaP, MMR and varicella vaccine) have only been thimerosal-free or contained only trace amounts of mercury (<1mcg per dose) from thimerosal as a residual from the manufacturing process, since the end of 2002.

 

The letter reviews that there were many of the following vaccines containing thimerosal throughout 2002 including:

 

?              Tripedia (DTaP, Aventis Padteur, 25mcg per dose)

?              Recombivax HB (hep B, Merck, 12.5 or 25mcg per dose)

?              Energix B (hep B, 12.5 or 25mcg per dose

The letter also reviews that the following thimerosal-containing vaccines were available in 2003:

?             Thimerosal-containing DT vaccine (Aventis Pasteur, 25mcg per dose)

?             Thimerosal-containing Td vaccine (Aventis Pasteur and Evans, for children 7 years of age or older, 25mcg per dose)

 

The Geiers had also stated that they had independently purchased vaccines to see which, if any, still contained non-trace amounts of thimerosal, and had found:

 

?              Meningococcal polysaccharide vaccine (Aventis Pasteur, 10 dose vial, 25mcg per dose

?              Td vaccine (Aventis Pasteur, 10 dose vial, 25mcg per dose

?              Tetanus toxoid absorbed vaccine (Aventis Pasteur, 10 dose vial, 25mcg per dose

?              Tetanus toxoid vaccine (Aventis Pasteur, 15 dose vials, 25mcg per dose

?              Japanese encephalitis virus vaccine (Aventis Pasteur, 35.7mcg per dose)

?              Influenza virus vaccine (Aventis Pasteur, 25mcg per dose

?              Td (Massachusetts PH Biological Laboratories, 8.3mcg per dose)

?              Pediatric DT vaccine (Aventis Pasteur, 25mcg per dose)

Many of these vaccines had 2005 expiry dates, so were available long after the advice to remove thimerosal.

 

34.   UK Vaccines With Thimerosal

 

Vaccines in the UK that are believed to still contain, or until very recently contained, thiomersal are:

 

?         DTaP (Diptheria and Tetanus and acellular pertussis) made by Lederle Laboratories

?         HIB (haemophilus influenza type B) made by Connaught Laboratories

?         DPT (Diptheria and tetanus and pertussis) made by Glaxo SmithKline

?         Energix-B (Hepatitis B) made by Glaxo SmithKline

?         HibTiter (Haemophilus influenza type B) made by Lederle

?         Fluvirin influenza virus vaccine made by Medeva Pharma

?         FluShield made by Wyeth-Ayerst

?         Menomune (Meningococcal polysaccharide vaccine) made by Connaught

?         Rabies vaccine made by Glaxo SmithKline

?         Recombivax (Hep B recombinant vaccine) made by Merck & Co.

 

In January 2003, a detailed report in The Scotsman newspaper listed four influenza vaccines in use in the UK (out of a total of seven) that still used thimerosal:

 

?              Fluvirin

 ?              Fluarix

?              Influvac

 ?              Agrippal

 

The UK Department of Health was quoted in the report, “There is no evidence of long-term adverse effects due to the exposure levels of thimerosal in vaccines”.

 

By early 2004, the UK was believed to be the last developed country in the world not to have acted to withdraw thimerosal from infant vaccines, and to be continuing to openly defend its use.

 

The UK National Health Service stocks two DTP vaccines, DTwP, which contains thimerosal and which is routinely offered, without warning or advice, and DTaP, which is labelled Infanrix and which is thimerosal-free. Infanrix is available to parents who demand it, but DTwP, made by Aventis Pasteur, is cheaper, and so remains the standard issue.

 

It is also understood that the UK introduced an accelerated schedule of DPT vaccination in the late 1980s/early 1990s, which would have significantly increased the thimerosal intake of infants.

 

It is known that MMR does not contain thiomersal, but it is thought that thiomersal may be used in its manufacturing process.

 

When the thimerosal issue was reviewed in the UK general practitioners’ magazine Pulse, the report concluded: “Another drawn-out public debate might damage public confidence, and falling vaccine uptake rates could cause the resurgence of preventable diseases”. This may be true, but this approach is also a potential charter for complacency and secrecy. Always, there is this first concern over “confidence”. At what point should safety concerns be publicly debated? Safety concerns in other industries, such as air travel, are not swept under the mat to preserve public confidence, but are independently investigated. Why are vaccines different?

 

35.   UK Medicines & Healthcare Regulatory Agency Position On Thimerosal

 

?         In May 2001, the UK Medicines Control Agency (now part of the Medicine & Healthcare Regulatory Agency) instructed manufacturers to warn doctors and patients of potential allergic reactions to vaccines containing thimerosal.

 ?         However, unlike the US, the UK has not moved to remove existing stocks, which are being used up.

 ?         The magazine Pulse also reported that the UK Government planned to reduce levels of thimerosal in infant vaccines, including DTP, HiB and the pre-school DT booster.

 ?         It also reported that the UK Government was set to adopt guidance from the European committee for proprietary medicinal products, urging manufacturers to implement a stepwise reduction in thimerosal levels in vaccines.

 

36.     UK Joint Committee On Vaccination and Immunisation Position On Thimerosal

 

These are extracts from the JCVI minutes of November 2001:

 

“Although the CSM (Committee on Safety of Medicines) had expressed some concerns about the limitations of the US study data (presumably this referred to Verstraeten), it had concluded that the preliminary results provided no coherent evidence of harm from thimerosal”

 

“They (the CSM) also felt that an extrapolation from methylmercury to ethylmercury (as contained in thimerosal) was not necessarily justified. Although CSM would continue to keep this issue under review, it had been reassured by what it had seen, and confirmed its view that there was no evidence that thimerosal in vaccines was harmful.”

 

“Further studies investigating the effect of thimerosal in vaccines were being conducted by the Public Health Laboratory Service (presumably Dr. Elizabeth Miller), one with WHO funding (Note: Dr. John Clements of the WHO had been part of the confidential Simpsonwood meeting to discuss the original Verstraeten study, where a 2.48 relative risk factor for autism after receipt of thimerosal-containing vaccines had been unveiled to a dismayed audience) and one with UK Department of Health funding. The Joint Committee would see the results of these studies when they were completed”.

 

“The Committee was reassured by the evidence that mercury exposure in the UK immunisation was very low. It confirmed its view that the available evidence did not indicate any hazard from the presence of thimerosal in vaccines, but that......thimerosal should nevertheless be withdrawn from vaccines wherever possible......”

 

But use of thimerosal continued:

 

“Based on the conclusions of (expert groups), there is no reason on the grounds of safety to change the current immunisation practices with thimerosal-containing vaccines.....The public should continue to have confidence in the immunisation programme, which has an enviable safety record”  -  Dr. Syed Ahmed, immunisation co-ordinator and Dr. Jim McMenamin, consultant in public health medicine, Greater Glasgow NHS Board, Glasgow, UK

 

This stance was endorsed in the Scottish press in June 2003 by Dr. Andrew Fraser, deputy chief medical officer, Scottish Health Department:

 

“Advice from the World Health Organisation (WHO) makes clear that the risk of death and complications from vaccine-preventable diseases is real, compared with the theoretical risk from side-effects of thimerosal”.

 

“No course of treatment is ever risk-free. The balance of risks, though, for the DTP vaccine (which had featured in adverse press comment) comes down strongly in favour of its use.”

 

Sallie Bernard of Safe Minds responded:

 

“Contrary to what Drs. Ahmed and McMenamin assert in their letter, in the October 2001 Institute of Medicine report, the thimerosal review committee concluded that “the hypothesis that exposure to thimerosal-containing vaccines could be associated with neurodevelopmental disorders.....is biologically plausible”......(and) “the committee recommends the use of the thimerosal-free DTaP, Hib and Hep B vaccines in the US”. She also pointed out a third conclusion: “The committee recommends that full consideration be given by professional societies and government agencies to removing thimerosal from vaccines administered to infants, children or pregnant women in the US”.

 

In an unpublished response to Dr. Fraser’s letter she stated:

 

As Dr. Fraser should know, the WHO in their investigation simply looked for existing studies on thimerosal safety. Finding none, since proper safety studies have never been conducted on this mercury compound, the WHO declared ‘no evidence of harm’”.

 

The US report (from the Committee on Government Reform, in 2003) strongly criticised the FDA for its continued assurances to the public of thimerosal safety when in fact it had no supporting data. Now Dr. Fraser is using the same distortion to placate the Scottish public”.

 

Dr. Fraser also misleads (Scottish) readers by suggesting that a little neurotoxic mercury is fine for babies because getting diphtheria, tetanus or pertussis disease is much worse. The argument is a false one, since the UK already has an effective licensed DTP vaccine (Infanrix) that does not contain thimerosal.....Thus to claim that Scottish parents must trade-off childhood diseases against mercury injections is absurd.”

 

37.   US Center for Disease Control Thiomersal Studies

 

At the hearing of the US House of Representatives Committee on Government Reform in June 2002 (see elsewhere for further details), several studies on the thiomersal issue were outlined by the US CDC representative, Dr. Roger Bernier:

 

(study one) This is the thimerosal Screening Analysis in the US Vaccine Safety Datalink (VSD) Project, which commenced Autumn 1999. Data from two health management organisations (HMOs) with automated outpatient data is screened. The CDC and VSD researchers found statistically significant associations between thimerosal and neurodevelopmental disorders such as language and speech delays, attention deficit hyperactivity disorder, stuttering and tics. No association was found with autism.

 

The associations were weak and varied between HMOs. A third HMO has since been examined. This did not confirm the results of the first study phase. These results require further examination.

 

(study two) This is the Thimerosal Follow-Up Study. This will be designed to assess whether preliminary results from automated data used in study one can be confirmed using objective neuropsychological testing. The study will focus on the same developmental disorders as study one. Results are expected by the end of 2003.

 

Three other studies are planned, with results not available until 2005 or later.

 

The US CDC has been heavily criticised by parents’ groups over its stance on access to the Vaccine Safety Datalink (VSD) database. The US group Safe Minds openly challenged the CDC to open VSD data to all qualified university-based researchers, but the CDC refused. The current position is that:

 ?              The CDC’s National Immunization Program has offered to provide limited access to selected areas of data which CDC personnel will choose and manually extract

 ?              Only researchers whom the CDC approves will be allowed this restricted access

 ?              Researchers must come to the CDC’s Center for Health Statistics to conduct their work

 ?              Before leaving, researchers must submit their analyses for review by CDC personnel, who will edit their findings

 

38.     Report, Mercury in Medicine  -  Taking Unnecessary Risks, prepared by the Subcommittee on Human Rights and Wellness, Committee on Government Reform, United States House of Representatives, May 2003, As A Result Of A Three-Year Investigation

 

This is a summary of the report’s key sections, verbatim:

 

?              In 1999, following up on the FDA evaluation.....the House Committee on Government Reform initiated an investigation into the dangers of exposure to mercury through vaccination.....In January 2003, the investigation continued in the newly-formed Subcommittee on Human Rights and Wellness

 

?              In July 2000, it was estimated that 8,000 children a day were being exposed to mercury in excess of Federal guidelines, through their mandatory vaccines

?              According to the (FDA), “at the heart of all FDA’s product evaluation decisions is a judgment about whether a new product’s benefits to users will outweigh its risks. No regulated product is totally risk-free, so these judgments are important. FDA will allow a product to present more of a risk when its potential benefit is great  -  especially for products used to treat serious, life-threatening conditions”

?              This argument  -  that the known risks of infectious diseases outweigh a potential risk of neurological damage from exposure to thimerosal in vaccines  -  is one that has continuously been presented to the Committee by Government officials. FDA officials have stressed that any possible risk from thimerosal was theoretical, and that no proof of harm existed.

?              The Committee did in fact find evidence that thimerosal posed a risk. The possible risk for harm from either low-dose chronic or one-time high-level (bolus dose) exposure to thimerosal is not “theoretical” but very real and documented in the medical literature

?              Congress has long been concerned about the human exposure to mercury through medical applications. As a result of these concerns, in 1997 Congress instructed the FDA to evaluate the human exposure to mercury through drugs and foods. The FDA realised that the amount of ethylmercury that infants were exposed to in the first six months of life through their mandatory vaccinations exceeded the Environmental Protection Agency’s (EPA’s) limit for a closely associated compound methylmercury

?              The FDA and other Federal agencies determined that in the absence of a specific standard for ethylmercury, the limits for ingested methylmercury should be used for injected ethylmercury. The Institute of Medicine, in 2000, evaluated the EPA’s methylmercury standard and determined that, based upon scientific data, it rather than the FDA’s was the scientifically validated safe exposure standard.

?              Rather than acting aggressively to remove thimerosal from children’s vaccines, the FDA and other agencies within the Department of Health and Human Services (HHS) adopted an incremental approach that allowed children to continue to be exposed to ethylmercury from vaccines for more than two additional years. In fact, in 2001, the Centers for Disease Control and Prevention (CDC) refused even to express a preference for thimerosal-free vaccines.

?              Many parents, and a growing number of scientists, believe that this mercury exposure may have contributed to the explosive growth in autism spectrum disorders and neurological and behavioural disorders that this country has experienced.....The Federal government has an obligation to vigorously pursue the necessary research to determine the extent of the impact of these heightened exposures to ethylmercury on our population

 

The Committee’s findings and recommendations included:

 

?              Manufacturers of vaccines and thimerosal.....have never conducted adequate testing on the safety of thimerosal. The FDA has never required manufacturers to conduct adequate safety testing on thimerosal and ethylmercury compounds

?              Studies and papers documenting the hypoallergenicity and toxicity of thimerosal have existed for decades

?              Autism in the US has grown at epidemic proportions during the last decade.....At the same time that the incidence of autism was growing, the number of childhood vaccines containing thimerosal was growing

?              A growing number of scientists and researchers believe that a relationship between the increase in neurodevelopmental disorders of autism, attention deficit hyperactivity disorder and speech or language delay, and the increased use of thimerosal in vaccines, is plausible and deserves more scrutiny

?              The amount of ethylmercury to which children were exposed through vaccines prior to the 1999 announcement exceeded two safety thresholds established by the Federal government for a closely-related substance, methylmercury

?              While the Federal Government has established no safety threshold for ethylmercury, experts agree that the methylmercury guidelines are a good substitute. Federal health officials have conceded that the amount of thimerosal in vaccines exceeded the EPA threshold of 0.1mcg per kilogram of body weight. In fact, the amount of mercury in one dose of DTaP or Hep B vaccines (25mcg each) exceeded this threshold many times over.

?              Federal health officials have not conceded that this amount of thimerosal in vaccines exceeded the FDA’s more relaxed threshold of 0.4mcg per kilogram of body weight. In most cases, however, it clearly did (Note: and using body weight as a measure is very crude  -  what about genetic susceptibility, difficult to measure but probably far more crucial)

?              The CDC’s failure to state a preference for thimerosal-free vaccines in 2000 and again in 2001 was an abdication of their responsibility. As a result, many children received vaccines containing thimerosal when thimerosal-free alternatives were available

?              No amount of mercury is appropriate in any childhood vaccine

?              The CDC in general and the National Immunisation Program in particular are conflicted in their duties to monitor the safety of vaccines, while also charged with the responsibility of purchasing vaccines for resale as well as promoting increased immunisation rates

?              There is inadequate research regarding ethylmercury neurotoxicity and nephrotoxicity

?              There is inadequate research regarding the relationship between autism and the use of mercury-containing vaccines

?              To date, studies conducted or funded by the CDC that purportedly dispute any correlation between autism and vaccine injury have been of poor design, under-powered and fatally flawed. The CDC’s rush to support and promote such research is reflective of a philosophical conflict in looking fairly at emerging theories and clinical data to adverse reactions from vaccines

?              Access by independent researchers to the Vaccine Safety Datalink database is needed for independent replication and validation of CDC studies regarding exposure of infants to mercury-containing vaccines and autism. The current process to allow access remains inadequate.

?              Congress should enact legislation that prohibits Federal funds from being used to provide products or pharmaceuticals that contain mercury, methylmercury or ethylmercury, unless no reasonable alternative is available

?              Congress should direct the National Institutes of Health (NIH) to give priority to research projects studying causal relationships between exposure to mercury, methylmercury and ethylmercury to autism spectrum disorders, attention deficit disorders, Gulf War Syndrome and Alzheimer’s Disease

 

39.     Letter to Congress by the US Office of Special Counsel, Washington

 

A major development in May 2004 was the issuing of a letter to Congress by the US Office of Special Counsel. The letter, from Special Counsel Scott J. Bloch, was directed to the Honorable Judd Gregg, Chairman, Committee on Health, Education, Labor and Pensions and to the Honorable Joe Barton, Chairman, Committee on Energy and Commerce, US House of Representatives.

 

The letter included the following verbatim quotes:

 

“As Special Counsel, if I find on the basis of the information disclosed, that there is a substantial likelihood that one of  these conditions (Note: this referred to alleged violations of law, rule or regulation, gross mismanagement, gross waste of funds, abuse of authority or a substantial and specific danger to public health or safety)....I am required to advise the appropriate agency head of my findings, and the agency head is required to conduct an investigation of allegations and prepare a report

 

“I have recently received hundreds of disclosures from private citizens alleging a widespread danger to the public health, specifically to infants and toddlers, caused by childhood vaccines which include thimerosal

 

It appears there may be sufficient evidence to find substantial  likelihood of a substantial and specific danger to public health caused by the use of thimerosal/mercury in vaccines because of its inherent toxicity

 

“Due to the gravity of the allegations, I......hope that you will review these important issues and press Health and Human Services for a response to this very serious public health danger.

 

“The disclosures allege, amongst other things, that:

 

?              some datasets showing a relationship between thimerosal/mercury and neurological disorders no longer exist

?              That independent researchers have been arbitrarily denied access to Centers for Disease Control and Prevention databases

?              That Government-sponsored studies have not assessed the genetic vulnerabilities of sub-populations

?              That the Food and Drug Administration colluded with pharmaceuticals companies at a conference at Norcross Georgia (Note: this was the Simpsonwood meeting) in June 2000 to prevent the release of a study which showed a statistical correlation between thimerosal/mercury exposure through pediatric vaccines and neurological disorders, including autism

?              The author of the study, Dr. Thomas Verstraeten, later published a different version of the study in the November 2003 issue of Pediatrics (Note: the original and re-worked versions are both detailed elsewhere in this Briefing Note), which did not show a statistical correlation. No explanation has been provided for this discrepancy

?               There is an increasing body of clinical evidence on the connection of thimerosal/mercury exposure to neurological disorders which is being ignored by Government public health agencies

 

“Based on what is known to date about mercury as a deadly neurotoxin and because thimerosal is not an essential component to the vaccine, there is no reason to continue to purposefully inject it into the bloodstream of infants

 

“I believe these allegations raise serious continuing concerns about the administration of the nation’s vaccine program and the Government’s possibly inadequate response to the growing body of scientific research on the public health danger of mercury in vaccines.”

 

The Office of the Special Counsel does not have jurisdiction over disclosures from private citizens. In the event, however, that a federal employee comes forward with information on this issue, the OSC would then have jurisdiction to determine whether there is a substantial likelihood that the information discloses a violation of any law, rule or regulation, or a substantial and specific danger to public health and safety.

 

40.     California Votes To Ban Thimerosal

 

In June 2004, the State of California‘s Senate Health and Human Services Committee voted 9 votes to 1  to ban the administration of mercury-containing vaccines that contain more than trace amounts of mercury (as per the US Food and Drug Administration’s definition) in pregnant women and children under three years of age.

 

PART E:

 

REVIEWS QUESTIONING THE AUTISM EPIDEMIC

 

Despite the evidence that autism has increased very greatly since the 1970s and early 1980s, several researchers maintain that this is not the case.

 

41.     Paper by Fombonne, Medical Research Council Child Psychiatry Unit and Institute of Psychiatry, Is There An Epidemic of Autism?, Pediatrics, January 2001

 

At the end of January 2001, a paper, “Is There An Epidemic of Autism?” was published by Dr. Eric Fombonne. The paper sought to deny that autism had really increased, and criticised the “poor research methodology” of Dr. Andrew Wakefield, and said “There is no need to raise false alarms on putative epidemics nor to practice poor science.....”

 

?         Fombonne criticises the California increase on the basis of in-migration, possible changes within the population make-up, the change from DSM-III to DSM-IIIR in 1987, the introduction of diagnostic categories for Asperger, Rett and childhood disintegrative disorder in DSM-IV in 1994, the effects of earlier diagnosis adding to the totals, and other factors.

 ?         His most useful conclusion is that “we simply lack good data”. He raises doubts about the apparent epidemic, but is then unable to refute it either.

 

In an excellent FEAT (parents’ group) critique (8th Feb 2001), Mark Blaxill goes carefully through Fombonne’s previous work and argues that Fombonne has become inconsistent. He points out key flaws in Fombonne’s previous work, and criticises his criticisms of the California data and his scientifically-unsupported assertions

 

42.     Paper by Lorna Wing, Centre for Social & Communication Disorders, Elliot House, Bromley, Kent, UK and David Potter, UK National Autistic Society, The Epidemiology of Autistic Spectrum Disorders: Is The Prevalence Rising?, 2002

 

This paper noted that:

 

?              For decades after Kanner’s original paper in 1943, autism was generally considered to be a rare condition with a prevalence of around 2 to 4 cases per 10,000 children. Then in the late 1990s, prevalence rates of up to 60 cases per 10,000 for autism, and even more for the whole ASD spectrum, were reported.

 ?              Reasons for this included changes in diagnostic criteria, development of the concept of the wide autistic spectrum, different methods used in studies, growing awareness and knowledge amongst parents and professionals, the development of specialist services, and the possibility of a true increase in numbers.

 

The paper argued that not one of the possible environmental causes, including MMR, had been confirmed by independent scientific investigation

 

The paper maintained that there was “strong” evidence that complex genetic factors played a major role in aetiology (Comment: this point and the one above seemed to be treated as “either/or” explanations rather than in combination)

 

In direct contrast with the 2002 California paper, this paper concluded that “the evidence suggests that the majority, if not all, of the reported rise in incidence and prevalence is due to changes in diagnostic criteria and increased awareness and recognition of autistic spectrum disorders. Whether there is also a genuine rise in incidence remains an open question”.

 

43.     Position of Dr. Bryna S. Siegal, Director, Pervasive Developmental Disorders Center, University of California at San Francisco, 2002

 

The August 2002 issue of Paediatric News carried a report by Sherry Boschert, about the position of Dr. Bryna S. Siegal of California, expressed at a meeting on developmental disabilities sponsored by the University of California at San Francisco. Dr. Siegal’s view is that:

 ?              Prevalence in autism in California increased from 5 per 10,000 in 1987 to 15 per 10,000 in 1994, yet during the same time, diagnosis of mental retardation declined by a similar amount, dropping the State prevalence of mental retardation from about 27 per 10,000 to around 18 per 10,000.

 ?              Changing social attitudes have shifted stigma away from autism and onto mental retardation

 ?              Autism is partly now preferred because it is associated with a higher level of State services. Dr. Siegal claims that many letters from parents actively seek a diagnosis of autism

 ?              These are not the only factors fuelling what she describes as an “illusory” epidemic of autism. The inclusion of the diagnosis of pervasive developmental disability into the former DSM-III classification in 1980, creating DSM-IIIR (or III-revised) resulted in autism rising by one-third. In 1994, the creation of DSM-IV, which included Aspergers cases, further increased the numbers.

 

Comment: these views have been strongly contradicted by:

 ?              The views of parents, professionals and others, who testify that autism is now being seen in unprecedented numbers

 ?              The point that the autism of the past largely comprised children who were autistic from birth or from a very young age, and that the “new variant” regressive autism was apparently largely unseen and unreported until the late 1980s, and that it is extremely unlikely that dramatic regression and loss of milestones would have been missed in the past

 ?              Detailed research carried out by Dr. Robert S. Byrd in late 2002 (reported elsewhere in this note), in California, finds that the apparent increase in autism is real, and not ascribable to reassignment from other categories

 

44.    Study by Croen, Grether, Hoogstrate and Selvin for the California Department of Health Services, July 2002

 

The authors conducted a population-based study of eight successive birth cohorts to examine the degree to which improvements in detection and changes in diagnosis have contributed to the observed increase in autism prevalence. Children born in 1987-1994 who had autism were identified from State registries. To evaluate the role of diagnostic substitution (re-assignment from other categories), trends in prevalence of mental retardation without autism were also investigated.

 ?              A total of 5,038 children with full-syndrome autism were identified from 4,590,333 births, giving a prevalence of 11 per 10,000

 ?              During the study period, prevalence of autism increased from 5.8 per 10,000 to 14.9 per 10,000

 ?              During the same period, the prevalence of mental retardation without autism decreased from 28.8 per 10,000 to 19.5 per 10,000.

?              The data, in the view of the researchers, suggests that improvements in detection and changes in diagnosis accounts for the observed increase in autism. However, they also conclude: “Whether there has also been a true increase in incidence is not known”.

 

Comment:  this report backs the views of Dr. Siegal (see above) and Dr. Fombonne (see below), but contradicts the study by Dr. Byrd (see elsewhere). The authors also acknowledge that there study cannot rule out that there has been a real increase. The criticisms applied to Dr. Siegal’s work also apply here.

 

A detailed commentary on the Croen et al study was published by Blaxill et al in the Journal of Autism and Developmental Disorders, Vol 33, No. 2, April 2003, criticising the following errors:

 

  *     they did not consider the trend information within their own dataset

  *     they did not consider obvious ascertainment biases within their youngest autism cohorts

  *     They did not consider similar ascertainment biases in the mental retardation category

  *     they did not analyse the implications of their own records review

  *     they did not define a key element of their principal disease frequency measure prevalence

 

And that correcting the first four of these errors is sufficient to controvert the authors’ argument.

 

45.     Fombonne, editorial, Journal of the American Medical Association, January 1st 2003 Vol 289, No.1 49

 

At the start of 2003, Dr. Eric Fombonne wrote an editorial in the Journal of the American Medical association that appeared to acknowledge that there had been some real increase in autism, but which also attempted to explain this away to as great a degree as possible through the usual recourse to references to better awareness, less restrictive criteria and a greater willingness to diagnose.

 

Fombonne’s key points were that:

 

?              That the prevalence rate of 34 per 10,000 (1 in 294) was likely to actually be an underestimate, because high-functioning autism cases were likely to have been missed.

 ?              The lower reported prevalence in 3- and 4-year olds might reflect lower sensitivity of case identification for disorders, which were often diagnosed later

 ?              There was an unexpected decrease in prevalence amongst 9- and 10-year olds. Fombonne dismisses the idea that this might imply that the younger the birth  cohort, the greater the level of autism as being “biologically implausible”. Yet this is open to obvious question  -  what if an external factor had altered during this time? Fombonne does not address this possibility.

 

Fombonne concluded that a rate of 41-45 per 10,000 (1 in 222) might be a more accurate rate of prevalence. He noted in his editorial that other studies suggested rates of 60 per 10,000 when pervasive developmental disorder-not otherwise specified (PDD-NOS) and Aspergers syndrome were taken account of.

 

He then addressed the issue as to whether the prevalence of autistic spectrum disorder (ASD) had increased over time. His benchmark was the 1970s Wing and Gould study in Camberwell, London, which pointed to a rate of 20 per 10,000 for severe-impairment cases. Other earlier studies had point to rates of 4 or 5 per 10,000, and more recent studies cited by Fombonne pointed to rates of more than 10 per 10,000. Fombonne’s conclusion was that the most recent rates of prevalence were three or four times higher than 30 years ago.

 

Fombonne, seemingly searching for an uncontroversial explanation for any increase, then examined whether this increase implied a broadening of criteria and improved methods of case-finding during studies. He pointed to what he described as the “major” changes in criteria:

 ?              Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III), 1980

 ?              DSM Revised Third Edition (DSM IIIR), 1987

 ?              DSM Fourth Edition (DSM IV), 1994.

 

He argued that there was strong evidence that differences in methods for case finding could account for a “huge” proportion of the variability of prevalence estimates between surveys. Referral rates were also unreliable, due to confounding factors.

 

This, and other factors, he concluded, combined to offer “good” evidence to support the contention that higher rates of prevalence reflected changes in diagnostic practice, improved identification and availability of services. The hypothesis of an increasing trend in the incidence of autism could not, in his view, be fully tested because of the inadequacy of studies to date. Fombonne dismissed any association with MMR (citing his own study work and studies by Madsen and by Taylor and Miller as proof), and dismissed evidence of any connection with thiomersal as being “weak”.

 

Fombonne was also quoted in the New York Times of 31st December 2002 as stating: “No strong candidate environmental exposures have been identified.....Claims of an association with MMR have not been borne out by recent studies, and evidence for causal association with other exposures such as mercury-containing vaccines is weak”.

 

The study being commented on by Fombonne was that by Dr. Marshalyn Yeargin-Allsop et al, detailed earlier.

 

Comment: the editorial by Fombonne offers no hard evidence against a vaccine/autism link, and, whilst offering some arguments in favour of questioning the precise scale of the apparent major rise in autism prevalence, fails to demolish the central assertion of many parents, that autism has grown immensely in a couple of decades. No alternative explanations for the rise are offered by the Fombonne editorial.

 

46.    Jick et al, Boston University School of Medicine, Increase in Autism is Due to Changes in Diagnosis, Pharmacotherapy, 2003; 23; 1524-30, December 2003

 

This study set out to identify whether the number of diagnosed cases of autism had progressively increased over the previous decade, and, if it had, what environmental factors were related to any increase.

 

The study documented numbers of children in the UK diagnosed with behaviour and developmental disorders and with autism. It found that numbers of children with behaviour and developmental disorders tended to decrease by about 20% per year, 1992-2000, whereas the diagnosis of autism increased by 20% per year during the same time period.

 

The conclusion of the study was that increased incidence of diagnosed autism is primarily a reflection of changes in diagnostic practices, such as improved identification. The authors did acknowledge that there had been a major increase in autism diagnoses.

 

The researchers also compared 126 autistic boys with non-autistic male controls. It found that there was no difference in the frequency of medicines or vaccines received by autistic cases compared with controls. There was no differences in medicines or illnesses between mothers of the two groups.

 

The study concluded that neither medicines (including vaccines) nor medical illnesses were responsible for the increase in autistic children. The study author, Jick, claimed that it “provides compelling evidence that vaccines, including MMR, are not the cause of the rise (in autism)”.

 

The study prompted comforting headlines in the UK press, such as “Autism Rise May Be A Myth” (Sunday Times, UK, January 2004). Jick commented: “This represents compelling evidence that the children haven’t changed but the diagnosis has”. However, there was a note of caution, that the authors “do not rule out the possibility that MMR or another drug might trigger autism in an individual child, but that it cannot be responsible for the large rise.”

 

Comment: it is mathematically impossible for cases of developmental disorders to decrease 20% year-on-year as cases of autism increase year-on-year as a consequence of the decrease. The numbers will not fit. This suggests that either the data of this study is suspect, or its interpretation is flawed, or that the claims being made of it are not supported by the data.

 

Comparing administration of medicines and vaccines between autistic/non-autistic groups proves nothing, and is irrelevant to the MMR debate. No one is claiming that giving MMR, in itself, causes autism. There have to be other co-factors, such as the state of health of the child, the state of its immune system, and genetic susceptibility due to familial background.

 

The Jick study appears to hinge upon a simplistic and erroneous hypothesis. It therefore offers no evidence in relation to links with MMR. To describe this study as “compelling evidence” is wholly unwarranted. That such a study should be so highly acclaimed is in itself revealing.

 

PART F:  EVIDENCE THAT INCREASES ARE REAL

 

47:     Close-Up On California

 

California has probably the most useful and detailed autism data in the world, going back to 1970. Trends monitored there have a potential worldwide significance.

 ?         The rise in autism was first highlighted by a report Changes in the Population of Persons With Autism and Pervasive Developmental Disorders in California’s Developmental Services System, 1987 through 1998  -  A Report to the Legislature, tabled on March 1st 1998 by the Department of Developmental Services, Sacramento, California Health and Human Services Agency.

 ?         Department of Developmental Services data shows that a record number of professionally-diagnosed DSM-IV criteria autism cases are now entering the State system. The rate of increase actually appears to be accelerating.

?         Numbers have gone up 1994-2004 from 5,281 to 24,297.

?         Between January 5th 2004 and April 2nd 2004, California added 795 new cases of professionally diagnosed DSM-IV full-syndrome autism to its recording system. Those 795 cases averages 11 new cases per day, seven days per week. The new cases do not include any children under three. They also do not include children with “autism spectrum disorder”, such as PDD, NOS, Aspergers etc.

 ?         Historically, autism made up 3% of childhood disability in the State Developmental Services system. It now comprises 55% of new cases added to the system. Autism has been by far the fastest-growing disability, and is now the number one disability.

?         Eight out of ten persons (of all ages, not just children) with autism have been born since 1980 (1980 was the year that California mandated the full complement of childhood vaccines as a condition of school entry. MMR was also introduced in California 1979-80).

 

This does not include children with persistent developmental disorder, non-specific (NOS) developmental delays, Asperger’s or and other autistic spectrum disorder  -  it is therefore the tightest definition of the severe-case numbers. 

 

Statistics on autism in the individual regional centres in California, run by the state Department of Developmental Services, also show a sharp rise at each centre in the period 1998-2002:

 

(regional centre)

At 7th Jan 1998

At 3rd Jan 2002

Increase %

Alta

400

683

71%

Central Valley

150

361

141%

East Bay

606

1,087

79%

E. Los Angeles

443

976

120%

Far Northern

125

217

74%

Golden Gate

371

499

35%

Harbor

639

1,113

74%

Inland

568

1,195

110%

Kern

141

262

86%

Lanterman

418

842

101%

North Bay

215

350

63%

N. Los Angeles

742

1,746

135%

Orange

670

1,621

142%

Redwood Coast

76

103

36%

San Andreas

360

666

85%

San Diego

609

1,186

95%

San Gab/Pomona

581

937

61%

S. Central LA

549

874

59%

Tri-Counties

352

725

106%

Valley Mountain

153

373

144%

Westside

613

986

61%

(Statewide Total)

8,781

16,802

91%

 

Comment: the above suggests a major rise in autism incidence in California, as elsewhere.

 

48.     The MIND Study, California

 

Following mounting concern at the apparent steep increase in autism in California, an urgent study was launched by the MIND Institute. Its findings were released on 17th October 2002, and appear to finally confirm (but see other contradicting studies in the following section) that autism has risen steeply.

 

The study was led by Dr. Robert Byrd, whose team had previously enrolled 684 Californian children who were receiving services from one of the Department of Developmental Services regional centers. Byrd’s team systematically gathered information for children in two age groups, 7-9 year olds, and 17-19 year olds. These were drawn from families of 375 children with a diagnosis of full-syndrome autism, and families of 309 children with a diagnosis of mental retardation without full-syndrome autism.

 

The study findings were that:

 ?              The unprecedented increase in autism in California is real and cannot be explained away by artificial factors such as misclassification and criteria changes. Autism is on the rise in California and the study team does not know why

 ?     The observed increase cannot be explained by a loosening in the criteria

 ?              Some children reported with mental retardation and not autism did meet criteria for autism, but this misclassification does not appear to have changed over time

 ?              Because more than 90% of the children in the survey are native to California, major migration of children into California does not contribute significantly to the increase in autism

 ?              A diagnosis of mental retardation associated with autism had declined significantly between the two age groups studied.

 ?              The percentage of parent-reported regression (loss of milestones) does not differ between the two age groups studied

 ?              Gastrointestinal symptoms, including constipation and vomiting, in the first fifteen months are more commonly reported by parents in the younger group

 

Comment: the above study appears to offer firm evidence of a major rise in prevalence.

 

49.     Close-Up On New Jersey

 

Data on autism in New Jersey, recorded by the IDEA system for individuals with disabilities who require special education, suggest that there is a vast preponderance of cases amongst children/young people ages 6-21 amongst the youngest ages.

 

The following figures related to the position as at 1st January 2002:

 

age

6

7

8

9

10

11

12

13

nos

514

505

465

439

360

257

208

165

 

age

14

15

16

17

18

19

20

21

nos

145

124

81

73

58

63

30

14

 

The total number of cases was 3,501. This equated to an average of 219 for each age-year. One year later, the position had worsened noticeably:

 

age

6

7

8

9

10

11

12

13

nos

582

548

531

469

442

369

254

215

 

age

14

15

16

17

18

19

20

21

nos

175

150

130

84

81

50

59

18

 

?              The total number of cases by this time was 4,157, an increase of 18% over the year before.

?              The youngest three years average out at 554 cases.

?              The oldest three years average out at 42 cases.

?              The average numbers of autistic children diagnosed in the youngest three years is about 13 times that of the numbers in the oldest three years.

 

In an article published by the US Autism Autoimmunity Project at the end of December 2002, Dr. Ed Yazbak set out the evidence for there having been a huge rise in autism in Rhode Island, New Jersey:

 

?              The Special Education Census published yearly by the Rhode Island Department of Education listed 14 categories of primary disability, by school district. Two categories, autism, and behavioural disorders, had risen sharply.

 

?             Autism had increased by 1,115% (one thousand, one hundred and fifteen per cent) between 1994 and 2002 in Rhode Island schools. On 30th June 1994, there had been 41 students at the schools with a diagnosis of autism. By June 30th 2002, that number stood at 498.

 

?              The more restrictive diagnostic criteria of DSM IV had been used, exclusively, since 1994, and had remained unchanged. Rhode Island has one main diagnostic center, one paediatric psychiatric hospital and very few paediatric neurologists, so consistency in application of diagnostic criteria would be high.

 

Comment: the above seems to confirm that the recent very steep rises in California are also being witnessed elsewhere in the US.

 

50.     Atlanta Study, Prevalence of Autism in a US Metropolitan Area, by Yeargin-Allsopp, Rice et al, published in the Journal of the American Medical Association, 2003, Jan 1st, 289: (1): 49-55

 

This study was at last an acknowledgment at the US Center for Disease Control & Prevention that autism was at a higher real level than two decades ago. Its conclusions directly undermined the evidence of one of its participants, Dr. Coleen Boyle, to the US House of Representatives Government Reform Committee, only a short time earlier, that autism was a very rare condition.

 

?              The objective of the study was to determine the prevalence of autism among children in a major US metropolitan area, and to describe the characteristics of the study population.

 ?              The study looked at children aged 3 to 10 years in the counties of metropolitan Atlanta, in 1996. Cases were identified through screening and abstracting records at multiple medical and educational sources, with case status determined by expert review.

 ?              The results were that 987 children were identified, displaying behaviour consistent with DSM-IV criteria for autistic disorder, PDD-NOS or Asperger disorder.

 ?              The prevalence for autism was found to be 34 cases per 10,000

 ?              The conclusion was that the rate of autism found was higher than the rates from studies conducted in the US during the 1980s and 1990s, but was consistent with those of more recent studies.

 

Comment: this study, too, supports the view that autism has greatly increased. The study is notable for being a CDC-sponsored study, using CDC personnel.

 

51.     Paper by Gurney, Fritz, Ness et al, Analysis of Prevalence Trends of Autism Spectrum Disorder in Minnesota, published in Archives of Pediatric Adolescent Medicine, 2003, 157, 622-627

 

The purpose of this study was to quantify and characterise prevalence trends over time in ASD in Minnesota. The study conducted an age-period-birth cohort analysis of special educational disability data from the Minnesota Department of Children, Families and Learning from 1981-82 through the 2001-02 school years.

 

The study results were:

 

?              Prevalence rates of autism spectrum disorder rose substantially over time within single-age groups and increased from year to year within birth cohorts

 ?              Autism spectrum disorder prevalence among children aged 6 to 11 years increased from 3 per 10,000 in 1991-92 to 52 per 10,000 in 2001-02

 ?              All other special educational disability categories also increased during this period, except for mild mental handicap, which decreased slightly from 24 per 10,000 to 23 per 10,000

 ?              The study found that Federal and State administrative changes favouring identification of ASD corresponded in time with the increasing rates.

 

The study concluded that there were dramatic increases in the prevalence of ASD as a primary special educational disability, and that the trends show no sign of abatement. The study found no corresponding decrease in any special educational disability category to suggest diagnostic substitution as an explanation for the autism trends in Minnesota.

 

As to the extent that increases were real, the study sat on the fence. It confirmed huge rises, but suggested that there may have been underdiagnosis in the past. However, it did confirm that reassignment from other categories of disorder did not explain the increase, nor did it ascribe increases to criteria changes.

 

52.   Paper by Dr. F. Edward Yazbak, Autism In The United States  -  A Perspective, published in the Journal of American Physicians and Surgeons, vol 8 No. 4 Winter 2003

 

This paper brought together much of the evidence of an autism epidemic for the first time in a peer-review publication:

 

?              Autism has reached epidemic proportions in the United States. The increase cannot be attributed to changes in diagnostic criteria, which have actually become more restrictive.

?              The increasing number of patients afflicted with this serious disability will have an enormous effect on the economy

?              Studies of a potential relationship to childhood vaccines have been limited and flawed

?              The autism explosion since 1994 and DSM-IV is best documented in California.....Autism has become the predominant disability for which services are accessed in California. According to the most recent (Note: at that time) California Autism Report released in March 2003, cases of Type 1 autism increased by 97% in the last four years compared to 16% for cerebral palsy and 29% for mental retardation

?              There is every reason to believe that more children will develop autism in the coming years

?              When the children become adults and the parents are no longer there, the impact on society will be even greater, and the burden on the US economy will mount into trillions of dollars

?              To date, the US Centers for Disease Control and other US Government health authorities have not given enough attention to this serious epidemic (the same allegation could most certainly be levelled at UK Government agencies).

?              According to Bernard Rimland of the US Autism Research Institute, two clear trends have emerged. First, the incidence of autism has increased remarkably, becoming an ‘explosion’ in recent years, and secondly, there has been a distinct shift in the time of onset of autistic symptoms

?              According to Rimland, late-onset autism was almost unheard of in the 1950s, 1960s and 1970s, but today, such cases outnumber early onset cases by five to one

?              Parents in increasing numbers are reporting similar stories. A child.....who is developing socially and verbally on par for his age, suddenly stops acquiring new words and skills in the second year of life and then regresses, losing speech, cognitive abilities and social dexterity

?              Suggesting that a sudden and exponential increase in autistic disorders is not real, and results only from better diagnosis, amounts to denial

?              Genetic disorders have never presented as epidemics, and investing the scant available (research) resources solely in genetic research diverts them from the scientific exploration of more plausible environmental etiological factors

?              In accordance with the US Individuals With Disabilities Education Act.....the number of children aged 6 to 21 with autism in US schools rose steadily from 5,415 in 1991-92 to 118,602 in 2002

?              Autism is not a diagnosis that parents accept readily, or physicians make lightly, or that school authorities approve easily. It is probable that autism in US schools is actually under-diagnosed and that many less severe cases are labelled behaviour and communication disorders, in order to avoid the stigma and/or the added cost

?              In spite of all the above, some “experts” still claim that the spectacular increases in autism reported lately are simply the result of more liberal or less stringent diagnostic criteria

?              The only reasonable conclusion from this review is that the recent increase in autism in the US is real and significant

 

Dr. Yazbak’s conclusion was that emerging evidence suggested some relationship between MMR and thimerosal-containing vaccines and regressive autism, and that additional independent and unbiassed clinical studies must be conducted in order to determine all causes involved.

 

53.     Paper by Dr. F. Edward Yazbak, Autism Skyrockets In Quebec  -  A Secret No More, published by Red Flags Weekly, 25th January 2004

 

Dr. Yazbak also carried out research into the apparent steep rise in autism in Quebec. In this paper, he suggests that:

 

?              The recent 150% increase in autism in all school age groups, in itself disturbing, does not do justice to the seriousness of the situation facing the Province

?              The percentage of pre-schoolers with autism is almost double that of students in primary grades, and almost quadruple that in secondary grades, a clear indication that younger children are being diagnosed in increasing numbers

?              Although some of the increase will be due to better and earlier diagnosis, the number of young children with autistic disorders accessing the special education system and requiring specialised educational services has risen dramatically.

?             A total of 1,388 students with pervasive developmental disorders were registered in schools in the Province of Quebec in September of 2000. By September 2002 this had increased to 2,267, an increase of 63% in just two years.

?             There were 91 children with autism in Montreal schools in 1998. By 2003, this number had risen to 307, an increase of 237% in five years.

 

The autism situation for 2003 makes a disturbing comparison with that in 1971. In 2003, the estimated population of Canada was approximately 31.4m, of whom 25.1% were under the age of 19, divided-up as follows:

 

(age)

(percentage of total population)

0-4

5.4%

5-9

6.3%

10-14

6.7%

15-19

6.7%

 

The approximate population of Quebec was slightly under 7.5m in 2003, compared with slightly over 6m in 1971. Using prevalence estimates appropriate to the years in question, one can estimate that there were somewhere between 300 and 400 individuals with autistic disorders in the Province in 1971, compared with over 10,000 in 2003:

 

(year)

(population)

(pop. 0-18 yrs)

(prevalence)

(autism/PDD)

Year 1971

6,028,000

1,513,028

2/10,000

303

Year 2003

7,455,000

1,871,255

60/10,000

11,228

 

The most conservative evaluation should show that the increase in autistic disorders in Quebec has probably exceeded 3,000% in the last thirty years. It is unlikely that any other childhood disease has increased at the same rate.

 

PART G

 

STUDIES THAT HAVE BEEN USED TO DENY AN MMR/THIMEROSALAUTISM LINK

 

This section deals with the numerous recent official studies and reviews, many in the UK but some in the US or elsewhere, that “prove” there is no connection between autism and vaccination.

 

These studies, and reviews of studies, are exclusively epidemiological. In other words, they are based upon surveys of information such as patient records.

 

54.     Limitations Of Epidemiology  -  A Preface

 

The limitations of epidemiological studies are well-known, and were eloquently expressed recently:

 

“The validity of observational research depends on the validity of existing knowledge about the cause of the studied disease. In other words, causal association cannot be established by data from observational research alone. Supportive evidence from experimental research, including basic science and randomised trials, is essential.....In observational research, such as cohort study and case-control study, compared groups can differ in many features and are thus not truly comparable. Whether this built-in limitation can be overcome depends on whether all major confounding factors can be identified and appropriately controlled. Recognition and identification of confounding factors, however, require a comprehensive and in-depth understanding about the complex biological mechanism in pathogenesis. If the mechanism of a disease is poorly understood, some unexpected confounders probably remain unidentified and uncontrolled.....Data from observational research just cannot be used as the sole evidence to.....deny a causal link”  -  letter by Fang and Shau, Department of Internal Medicine, National Taiwan University Hospital, Tapei, published in The Lancet, Vol 360, No. 9328, 20th July 2002

 

As will be seen, all when scrutinised critically are actually either irrelevant, inconclusive, or are seriously methodologically questionable.

 

?         The UK Government’s advice on MMR and autism comes from the DoH, the Medicines Control Agency (MCA), the Committee on Safety of Medicines (CSM) and the Joint Committee on Vaccination and Immunisation (JCVI). These bodies are closely intertwined, and have based their position on a barely more than a handful of studies. Further advice has come from the Medical Research Council.

 ?         Much of the focus has been upon the need maintain public confidence in MMR to prevent communicable diseases, rather than the need to investigate specific cases of alleged damage.

 ?         The studies are also of random groups of children, but not of the actual children reported by parents as damaged by MMR.

 ?         Finally, the UK Department of Health has implied in the past that the evidence for a link between MMR and regressive autism has come from only one team of researchers, which is not factually correct. However, the very same criticism can be levelled at the “anti-link” camp. A significant proportion of the studies below only comes from a very small number of sources, some very close to the UK Department of Health itself.

?         Similar errors of logic have been committed in the US by the CDC and the Institutes of Health, and by the Institute of Medicine.

 

55.     Stokes et al Paper, Trivalent Combined Measles Mumps Rubella Vaccine, Journal of the American Medical Association, 4th October 1971

 

This paper, by Stokes, Weibel, Villarejos, Jorge, Arguedas, Buynak and Hilleman, has assumed more importance recently (see later Wakefield/Watson/Shattock debate section).

 ?         The paper stated that triple vaccines were desirable to simplify administration, reduce costs and minimise visits (my emphasis). There was no mention of greater effectiveness, or inherent drawbacks with single vaccines.

 ?         There were three trials, firstly of 30 children in Philadelphia, then of 214 children in Philadelphia, then of 440 children in rural Costa Rica and San Salvador, total 684 but (note) of very different economic and geographical backgrounds.

 ?         The mean ages of children in the three trials was 1.1, 1.5 and 3.0 years. Note that the present age of receiving MMR is about 14 months, and therefore the vast majority of the trial children were significantly older than today’s UK MMR recipients. Some 64% were also not from Western social/health backgrounds.

 ?         The 30 children’s parents were given report cards for recording temperatures for 28 days, and queried at six to nine weeks. For the 214 child-cohort and the 440 child-cohort trials, follow-up was 28 days. The parents were instructed to notify any significant illnesses during the 28-day period, and were queried at the second bleeding, six to nine weeks after vaccination  -  but the implication is that this query may have covered the 28-day interval, not longer.

 ?         The study noted that “the fifth to twelfth day after vaccination is the critical time period for occurrence of the expected low incidence of febrile reaction”, also that the significance of the difference between vaccinees and controls in terms of miscellaneous subsequent complaints (gastroenteritis included) was “doubtful” (though it was actually very marked in the study tables, up to 18/228 of vaccinees with gastroenteritis, compared with at most 3/106 of controls)

 ?         At no point in the study was autism mentioned as a risk-factor or an actual outcome. Clearly, the possibility was not even considered. The study noted the lack of arthritis and arthralgia.

 Overall verdict: this study is not relevant to disproving an MMR/autism link

 

56:     Study of Twins By Peltola and Heinonen, Frequency of True Adverse Reactions to MMR Vaccine; A Double-Blind Placebo-Controlled Trial in Twins, National Public Health Institute and Children’s Hospital, University of Helsinki, Finland, published Lancet, April 26th 1986

 

This study sought to check levels of adverse reactions following MMR. MMR was introduced into Finland in 1982, being administered at 14-18 months and at 6 years, using Merck Sharp Dohme Viravac.

 ?         The study was a double-blind crossover study involving 581 twins. The vaccines were administered blind, but one twin of each pair first received active MMR, then three weeks later, received a placebo. The other twin was given the placebo first, then three weeks later received MMR.

 ?         Each twin was given a colour coded questionnaire to be completed daily by parents, for 21 days after the injections.

 In theory, this should have provided a foolproof test of how reactive MMR was. However, the study completely founders on:

 ?         the issue of the potential time-delay between receipt of MMR and any possible gradual degeneration into autism. If such a delay could exceed 21 days, then the study would have missed it as an adverse reaction

 ?         Secondly, the linking of autism/developmental delays with MMR, or indeed any other vaccine. Parents in 1982, or indeed until about mid-1997, were not linking MMR with autism. It is extremely unlikely that regressive autism would have been connected, in the minds of either parents or the study authors, with MMR back in 1982. Virtually no literature or press reports had appeared on the issue.

 ?         As with the original safety trials of MMR (see later papers), this study was not designed to verify whether rare and complex adverse events might follow months or years after MMR.

 ?         The study only looked at one brand of MMR. As subsequently transpired, some brands of MMR used in the UK and elsewhere had a less satisfactory safety record than others, and (in the UK) were withdrawn at very short notice in 1992. A study with Viravac cannot be used to give safety clearance to other brands if the brands are found to have been variable.

 ?         A further criticism is that the study is still quite small in relation to rare events. It involved 581 twins. All other things being equal, if a rare adverse outcome occurred at a rate of 1 in 2 x 582, or less frequently, this study would not have found it.

 

The authors did actually acknowledge this, stating:

 ?         The study was designed to explore relatively common symptoms and signs occurring after the vaccination” (they mean, “within 21 days of”), and

 ?         Rare reactions due to the MMR vaccine cannot be studied with this small sample”.

 

It is therefore suggested that this study, regarded as the “gold standard” by the exponents of MMR, offers no evidence for or against an MMR/autism link; it is clearly irrelevant. Overall verdict: this study is not relevant to disproving an MMR/autism link

 

57:     Study by Miller, Miller, Rowe et al, Surveillance of Symptoms Following MMR Vaccine in Children, The Practitioner, Vol 233, 8th January 1989

 

This paper was to report the incidence and severity of clinical reactions before the start of the UK national MMR programme. MMR was offered to 10,000 children in three districts in the UK, with a post-vaccination follow-up of every child.

 

Two types of MMR were introduced, Immravax in Somerset, England, and Pluserix in Fife, Scotland, and North Hertfordshire, near London. Both vaccines contained Schwarz measles and Urabe 9 mumps vaccine, and both later had to be withdrawn in 1992 for safety reasons, in connection with risks of aseptic meningitis. These risks were not detected by this study.

 

The study found that:

 ?         Of the 7,247 children aged 1-2 years, 38% had either no symptoms or symptoms for only one day

 ?         18 had convulsions. Fifteen were admitted to hospital.

 ?         Of the children aged 4-5 years, 61% had either no symptoms or symptoms for one day. There were no convulsions and no hospital admissions.

 ?         Follow up was for 21 days. However, 114 children were followed up through diary records for a further 21 days, total 42 days.

 ?         Comparison of symptoms of children after MMR was made against symptoms of children after measles vaccination  -  not unvaccinated children.

 ?         The study concluded that symptoms reported after MMR appeared to be similar in nature, frequency, time of onset, and duration, to those recorded in earlier studies after monovalent measles vaccine

 

Comment: as with the original safety trials of MMR, follow-up was extremely short and only immediate/near-immediate reactions noted. The study did not look at autism, but effectively cleared the way for MMR’s general introduction into the UK. It is noteworthy that the study was co-authored by Dr. Elizabeth Miller, who subsequently authored or co-authored several of the studies that have been used as “proof” that there is no MMR/autism link. It is also noteworthy that, as noted, this study missed the aseptic meningitis problem of MMR, and that the brands of MMR with Urabe strain mumps virus subsequently had to be withdrawn, in 1992, at extremely short notice.

 

Overall verdict: this study fails to disprove an MMR/autism link

 

58.    Gillberg Study, Sweden, Is Autism More Common Than Ten Years Ago?, British Journal of Psychiatry, 1991, 158; 403-409

 

The paper reported a study in Sweden by Gillberg et al, 1991. It has been partially updated since (see below).

 ?         Gillberg looked at tiny sample of autistic children (55 of typical autism, just 19 of atypical autism), in Goteburg and Bohuslan. The study, actually a mish-mash of three studies with differing criteria, does not mention vaccination, does not state the coverage of MMR, does not include data on uptake or demographic factors, and is therefore irrelevant to the MMR/autism debate.

 ?         It had tracked down cases of autism unscientifically, by word of mouth, doctors etc., then allocated them by d.o.b. to “pre-MMR” and “post-MMR” eras

 ?         The study’s case-selection being a few cases out either way would neutralise or completely reverse the findings of the study.

 ?         The paper does acknowledge that the rate of autism has increased but “explains” this through changes in population structure and “better diagnosis”.

 Overall verdict: this study offers little evidence that MMR does not cause autism, particularly as it is so small.

 

59.     Paper by Gillberg and Heijbel, Commentaries, Autism, Vol 2 (4) 423-430, 1998

 

This further paper by Gillberg was published following the appearance of the Wakefield et al “Early Report” paper in The Lancet in early 1998.

 

Gillberg and Heijbel stated that they had re-analysed the data from their population study of autism performed in the late 1980s and published in 1991 (as above). The children in that study (n = 55) had been born in the ten-year period 1975-84. The authors claimed that as MMR was introduced in Sweden for 18-month-old children in 1982, with coverage increasing rapidly to 90%. The authors then argued that if there was an MMR/autism link, then children born from July 1980 onwards (i.e. The post-MMR generation) would be expected to be at increased risk. The 55 children were therefore divided into 34 (62%) pre-MMR and 21 (38%) post-MMR.

 

The authors then argued that had there been a strong effect of MMR, they could have expected more than 45% of the 55 cases of autistic children to have fallen into the post-MMR group. As this was not the case, then their study did not support the hypothesis of an association between MMR and autism

 

The authors also again claimed that in their parallel study of 19 atypical autism cases, there would have been a similar effect, and therefore that again there was no support for an association.

 

Overall verdict: as with the original study, these numbers were so small as to render this study, and its conclusions, as virtually without value in the context of proving/disproving an MMR/autism link. Statistical/epidemiological studies based upon cohorts numbering 55 and 19 cases are far too small. It is extraordinary that the UK Department of Health was using this study in the late 1990s to “disprove” the suggested association.

 

60.     Letter by Dr. Eric Fombonne, Inflammatory Bowel Disease and Autism, Pediatrics, March 28th 1998

 

This letter set out two studies that attempted to prove that there was no connection between inflammatory bowel disease/Crohn’s disease and autism. The first study looked at UK clinical data collected by the Child & Adolescent Psychiatric Services of the Maudslay Hospital, London.

 

?         For ASD, three diagnostic groups were examined, autism, atypical autism including disintegrative disorder, and pervasive developmental disorder

 ?         Medical disorders were coded for a 25-year period, including Crohn’s and ulcerative colitis, for 8889 patients.

 ?         Of the 8889 patients, 987 were born in 1987 or later, and were therefore most likely to have been exposed to MMR. Of these, 201 had ASD.

 ?         Of the 8889 children, only two had Crohn’s, and both were non-autistic. None had ulcerative colitis.

 

For the second study, a similar approach was undertaken. Fombonne surveyed medical, behavioural and intellectual disabilities amongst 6100 French children.

 ?         He found 174 cases with autism.

 ?         One child of the 6100 had Crohn’s, and one had ulcerative colitis. Neither were autistic

 ?         The conclusion that Fombonne drew was that these data provide no support for the hypothesis of an association between IBD and autism. 

 

Overall verdict: neither of these studies offer any evidence to disprove an MMR/autism link.

 

61.     UK Committee On Safety of Medicines Study, Report of the Working Party on MMR Vaccine, Committee on Safety of Medicines, June 1999

 

This study looked at the medical records of some of the children who are now taking High Court action. Their details were provided by their lawyers.

 

The study admitted:

 ?         Information on the children was extremely variable in quality and completeness

 ?         It was “difficult” to draw conclusions about any causal association (verbatim quote: “the information evaluated has important intrinsic limitations as regards assessing whether the vaccines are or are not causally associated with the adverse effects”)

 ?         It was not feasible to review the less common adverse side effects

 The study was effectively run as knockout competition. Each case had to pass four hurdles (all four) to be counted as being caused by MMR. The four hurdles were: (1) have either the diagnosis or clinically relevant signs/symptoms been confirmed medically? (2) was the onset of the possible adverse effect within six weeks of immunisation with MMR? (3) was there history prior to immunisation relevant to the possible adverse effect? (4) was there evidence of other causes for the possible adverse effect?

 

?         Six weeks after immunisation was chosen as a cut-off point for a close temporal association because (quote) “this is the maximum period in which viral replication can be detected after immunisation”. But this probably missed many cases, and is arbitrary. The Spitzer, Aitken et al study (see later) renders this six-week limit as irrelevant.

 ?         At every stage, the study looked for other “causes” to explain-away the cases, and took every opportunity to ascribe cases to these “causes”. In most cases, it was assumed at every stage without scientific justification that autism was “caused” by other factor rather than MMR. But it is not known what causes autism. Therefore there is a gross study bias, and the study rests upon unscientific assumptions.

 ?         The other assumed “causes” were the child’s previous medical history, comprising having a parent/sibling with speech or behavioural problems, an obstetric history of pregnancy complications (these, alone, were not considered as “causes”), signs/symptoms of encephalopathy, a head circumferences larger than the 97th percentile, or history of unspecified viral illnesses, bronchiolitis, rubella, measles, or a minor head injury.

 ?         The study eventually only looked at 92 cases of autism in detail (plus 15 Crohn’s), and was left with a residue of 8 autism cases and four of the Crohn’s it could not “explain” away. These were then just set aside, without explanation.

 ?         What the study did was to introduce so many extraneous considerations, and accord these such an importance, that hardly any case with sufficiently-clear documentation remained to survive the appraisal process. This eliminated almost all cases. The study then appears to have then simply set aside the residue.

 ?         The study text commented that (quote) “it was impossible to prove or refute the suggested associations between MMR vaccine and autism or inflammatory bowel disease because of the nature of the information.”. This would seem to inevitably render the study as inconclusive. But the study’s conclusions did not reflect this sentence.

 ?         The wording of the final conclusion left a small exit-route for any possible future U-turn: “”On the basis of all the available evidence, the demonstrated benefits of MMR or MR vaccines far outweigh any possible risks” (my emphasis).

 ?         The DoH’s press release 0342 of 1999 spun the study’s conclusions further  -  “Two New Independent Studies Have Not Found A Link Between MMR Vaccination And Autism

 

Note: this is the only study to date to have both looked at the actual children reported to have been damaged and to have “cleared” MMR. But as the above criticisms show, the study was actually self-admittedly inconclusive. It also failed to medically examine the actual children.

 

Overall verdict: this study does not disprove an MMR/autism link.

 

62.     Paper by Taylor, Miller, Farrington et al, Autism and Measles Mumps Rubella Vaccine: No Evidence for a Causal Association, Lancet 1999, 353, 2026-9

 

The study, designed by Dr Elizabeth Miller of the Public Health Laboratory Service, was wholly inconclusive, but has been widely presented as conclusive proof of the absence of any link between MMR and autism.

 

?         It only looked at 498 cases, far too small a sample for a robust statistical (case-series analysis) test. The study attempted to track-down children through special schools and local authority special needs registers  -  a method that is open to question, as it probably misses many cases. The study describes itself as “a large regional sample”, but it was actually very small.

 ?         Taylor, Miller found a steep increase in autism, (“There was a steady increase in cases by year of birth”), but did not explain it.

 ?         Also, the study looked for a time-clustering of parental concern six months after MMR, found it, but then dismissed it unconvincingly by saying it was “related to the difficulty of defining precisely the onset of symptoms”. But this method, of precisely identifying a date, was meant to be the very basis of their study.

 ?         Also, the study did not include in its post-MMR numbers those children born 1986-87 who later received it, nor those 2/3/4 year olds who had MMR at this older age.

 ?         It also missed children who had single vaccines, then MMR later. It not only misses these from “post-MMR” numbers, but added them to its pre-MMR numbers. The whole study is thereby compromised. The authors have since sought to clarify this in correspondence in The Lancet, but unconvincingly.

 ?         Autism is sometimes not diagnosed for years after. It is very difficult to pin down an actual “date” of diagnosis, and many children don’t receive any formal diagnosis anyway (contact National Autistic Society, which did a study on this, tel 0207 833 2299). The Taylor Miller study doesn’t recognise this.

 ?         The study seems to have been designed to clear MMR, not to test whether there is a link with autism. The study struggles, and fails, to disprove a link.

 ?         Also, the study is described by the UK DoH as “independent”. But Taylor was co-author of a 1988 paper clearing the safety of triple vaccines, Miller was described in Daily Express press reports of 1/01 as “a colleague of Dr David Salisbury” (head of the DoH Immunisation & Communicable Diseases Branch, which runs the MMR programme), and the study was funded by the UK Medicines Control Agency, a satellite of the DoH.

 ?         The authors have been repeatedly challenged by other researchers to release their raw data but have refused. Yvette Cooper, the UK Minister for Public Health, has backed up their refusal.

 

Overall verdict: despite its claims, this study cannot be taken as proof of there being no MMR/autism link, due to its apparent serious methodological flaws.

 

(Note: this study has been claimed by the UK Medical Research Council to represent “strong positive evidence” of there being no MMR/autism link)

 

63.     Paper by Miller and Farrington to US Government Reform Committee Hearings, Written Testimony to the Congress of the United States Committee on Government Reform Hearing On The Challenges of Autism  -  Why The Increased Rates, April 2001

 

In their submission to the US House of Representatives Committee on Government Reform Hearing, which was investigating increases in autism and possible links with vaccination, Miller and Taylor re-stated:

 

?         Our conclusion, based on the findings of our study, is that there is no evidence of a causal association between MMR and autism”.

 ?         “The case series method has a proven track record with respect to identifying and measuring a risk of adverse events after various vaccines”.

 ?         In our study, we showed that the increase in the prevalence of diagnosed autism in recent birth cohorts occurred during a time when the coverage of MMR vaccine in the same cohorts has been constant. The rise cannot therefore be related to the use of MMR vaccine.”

 ?         There is no credible epidemiological evidence to support the view that measles vaccination is a risk factor for Crohn’s disease or any other inflammatory bowel disorder”.

 

However, as explained in the section covering the original paper by Miller, Taylor and Farrington, there are major questions over the methodology of this paper; these, of course, can also be applied to Miller and Farrington’s paper to the Government Reform Committee.

 

64.    Patja, Peltola et al Study, Serious Events Rarely Related to MMR Vaccine: Natural Diseases Outweigh Risks, Pediatric Infectious Disease Journal, 2000;19; 1127-1134 (December)

 

This Finnish study, usually referred to as the Peltola study, concluded that serious events rarely were related to MMR. The study was initiated in 1982, when MMR was introduced. A nationwide surveillance system was set up to detect serious adverse events, reviewing patients’ clinical records and where taken, serum samples. However, the study relied on passive surveillance  -  a fatal flaw  -  and only followed up acute adverse events  -  a further fatal flaw.

 

According to the report,

 

?         173 potentially serious adverse reactions were claimed to have been caused by MMR, out of almost 3 million doses.

 ?         There were 77 neurologic reactions, 77 allergic reactions, 22 miscellaneous reactions and one death.

 ?         Some 45% of these reactions were dismissed by the study as probably caused or contributed by other factors.

 ?         Peltola admitted on BBC Radio 4 on 13/1/01 that the Finnish study was not designed to look at either autism or inflammatory bowel disease. He confirmed that the study was not specifically designed to look for autism, as no-one had ever raised this issue at the time.

 ?         The Peltola study simply identified the 173 children (out of 1.8m persons, including troops), who had acute reactions to MMR, then followed only these children up. The study followed up the wrong children. No-one has ever suggested that autism follows an acute reaction.

 ?         There would almost certainly have been potential autism cases amongst the remainder of the 1.8m, but these were missed, because they were excluded from the study, as it had a 3-week cut-off for reporting reactions. After that point, the remaining (theoretically, 1,799,827) children/other persons were ignored.

 ?         Peltola relied on referrals from health workers out in the field, who would never have connected degeneration into autism, several months/years after MMR, as being a potential adverse reaction to a vaccine. The alleged syndrome was not known of by scientists, let alone by health-workers in the field, at that time.

 ?         The UK DoH interpretation of this study, widely trumpeted during 1/2001, is that Peltola “clears” MMR of a link with autism/IBD. It is difficult to accept that this “conclusion” has any degree of scientific justification. It appears that the DoH’s “conclusions” have been retrospectively bolted-onto an old and irrelevant study.

 

There are other awkward facts regarding the Peltola study:

 ?         The study was part-funded by Merck Sharp Dohme (MMR manufacturers).

 ?         The study barely refers to autism or IBD.

 ?         Reviews of the study (eg December 2000 Medscape) do not even mention autism/IBD, which are obviously not seen by the reviewers as a relevant aspect of this study.

 

Despite this, the Peltola study continues to be cited by the UK medical establishment as conclusive proof that there is no link between MMR and autism. As late as 12/2001, Dr. Simon Fradd of the General Medical Council’s Doctor-Patient Partnership quoted this study by Peltola on BBC Radio 4 as conclusive proof of the absence of any link.

 

The UK DoH also said in a personal communication, referring to all the various studies: “the follow-up time (three weeks) was based on knowledge of the replication rates of the vaccine viral components.....it is recognised that such a study could not establish a causal relationship with extremely rare events..... millions of children have received MMR in other countries such as Finland and the USA; no serious long-term complications have been identified....” (my emphasis).

 

Overall verdict: this study is wholly irrelevant to the issue of whether MMR can cause autism.

 

65.    The Kaye, Melero-Montes and Jick Paper, MMR Vaccine and the Incidence of Autism Recorded by General Practitioners: A Time Trend Analysis, British Medical Journal, February 2001

 

This paper attempted to prove that there was no link between MMR and autism because, although autism increased when MMR was introduced, it has carried on increasing since, even though MMR’s coverage reached near-saturation almost immediately after its introduction into the UK in late 1988.

 

?         The study looked at 305 children (254 boys) aged 12 or under with autism diagnosed in the years 1988-99. It also looked at 114 boys aged 2 to 5 years born in 1988-93. It used the UK General Practice Research Database.

 ?         The study found that autism had increased sevenfold from 0.3 per 10,000 in 1988 to 2.1 per 10,000 in 1999 (note how low this figure is compared with other studies)

 ?         In the 114 boys born 1988-93, it found autism had increased fourfold, from 8 per 10,000 (1 in 1250) for boys born in 1988, to 29 per 10,000 (1 in 345) for boys born in 1993, during a period when MMR take-up was claimed to be constant at around 97%.

 ?         The study concluded that no correlation existed between MMR and autism, and that the explanation for increased autism remained uncertain

 ?         However, the authors acknowledge that their methods were a “second-best”, because what they really wanted to do was compare vaccinated and unvaccinated cohorts of children. They said that this was impossible because only 3% of cases and controls did not receive MMR. Given the very small numbers of autism cases they in the event actually looked at, this seems an unconvincing argument for abandoning their preferred approach

 ?         The authors then argue that if MMR was a major cause, then the risk of autism should have stopped rising within a few years.

 ?         However, they also admit that the diagnosis of autism was not confirmed from original records, but conclude that “differential misclassification of the diagnosis in vaccinated and unvaccinated children is unlikely to vary over the period of the study”, though no evidence is offered to back this claim.

 ?         They also acknowledge that time trend analysis is a “relatively crude method”.

 ?         The study authors go on to speculate that the increase in autism that they found “could be due to increased awareness of the condition among parents and GPs, changing diagnostic criteria or environmental factors”, without subjecting these “explanations” to any detailed scrutiny.

 ?         The authors also acknowledge the further limitation that they have not yet obtained and evaluated full clinical record information from GPs to describe more fully the characteristics of children diagnosed with autism and to explore other possible explanations. Yet they still dismiss MMR, despite this shortcoming.

 ?         It might be the case that the increase in autism that the authors find, over the period 1988 to 1997 (note - not 1999 - the study figures actually fall away after 1997) could be due to a hybrid explanation, with increases in the early years due to MMR and then continuing further increases in the later years due to better awareness. There is nothing in the study to refute this criticism

 ?         It is also unclear how the issue of re-vaccination has been dealt with. What of the seven million children vaccinated or re-vaccinated in 1994 in the UK “Operation Catch-Up” programme? Couldn’t the continuing rise in diagnosed cases in 1995-97 be due to Operation Catch-Up? The study does not mention it.

 ?         It is interesting that the Finland study team (Patja et al) said “Causality between immunisation and a subsequent untoward event cannot be estimated solely on the basis of a temporal relation.” Yet the Kaye et al study uses a basically similar approach to “prove” there is no link, comparing temporally-linked trends in MMR take-up and autism increases.

 ?         There is also a question over the use of mercury-based preservative (thiomersal, or thimerosal) in vaccines. This was used in the late 1980s and early 1990s, but has reported to have been largely phased-out in the US, with a free exchange system being operated by the manufacturers. No such exchange has operated in the UK, with existing thiomersal-based stocks being used up on the children. Autistic enterocolitis may involve thimerosal as part of the damage sequence.

 ?         If it did, and following a change in formulation, then this might well explain continued rises in autism through the 1990s, then a fall-away in increases at the end of the decade, as was actually found by Kaye et al. Did the industry change the preservative formulation as public concern grew? And has this affected the statistics of autism?

 

Overall verdict: this study offers no convincing evidence against an MMR/autism link.

 

66.      Paper by Dales, Hammer and Smith, Time Trends In Autism and in MMR Immunisation Coverage in California, Journal of the American Medical Association, March 7th 2001 Vol. 285, No. 9, 1183-1185

 

This paper is one of the least conclusive and least robust of all the research of recent years. It appeared in JAMA, March 7th 2001, but it is surprising that it achieved such a high profile within the UK, so weak was its hypothesis and so inconclusive its contents.

 

The paper attempted to determine if a correlation existed in trends of MMR immunisation coverage and autism occurrence. It did this by examining data from 21 regional centres covering the whole of the State of California.

 

During the years examined, 1980-94, MMR take-up was about 72% prior to 1988 and about 82% after 1988. Autism increased from about 200 in 1980 to about 1200 in 1994. The trend of increasing autism continued after the introduction of MMR and was claimed to be unaffected by the increase in take-up.

 

This hypothesis, of a correlation, could be criticised as not being useful to the detection of any MMR/autism link. Although immunisation coverage can be determined, with a specific “date of immunisation”, autistic spectrum disorder ranges from the mild to the severe, its onset ranges from the rapid to the gradual, and its diagnosis varies from a timely and accurate diagnosis to no diagnosis whatever. This apparently was not taken adequate account of by Dales et al.

 

The study did acknowledge some weaknesses itself:

 ?         Diagnosis is not always straightforward”. This is an extreme understatement.

 ?         California Department of Developmental Services’ report stresses that its patient caseload data cannot be used as a true measure of changes over time in autism incidence because other factors can affect trends in system case numbers

 ?         Observation of parallel trends over time.......generally do not constitute strong evidence for a causal association between the two events

 ?         As the system expanded and matured over time, the proportions of California children enrolling and the distribution of ages at enrolment likely (my emphasis) changed over time as a result”. Clearly, the authors do not know, one way or the other, not do they attempt to quantify this to enable their reliance on the data to be validated, or appropriate potential distortions in the data eliminated.

 ?         Also, the proportions of children enrolling in the system who were born outside California may (again, my emphasis) have changed over this time period”. Again, they do not know, have not attempted to quantify this factor, and cannot correct for it.

 ?         The data presented herein have some limitations. It would have been useful to examine individual immunisation and autism records on the same children; however, these could not be linked”. What the authors are saying here is, they would like to have done a rigorous study, but they couldn’t obtain the data.

 ?         Further, the childhood immunisation coverage data used in this study do not provide precise quantification of the percentage of children who received the combined MMR vaccine product vs. separate injections”. This is an admission that one element of the two elements that provide the statistical comparison that is central to their hypothesis, is inaccurate. They go on to say that historical data from elsewhere in the US “strongly suggests” that the use of separate vaccines was “rare” for the 1984-94 birth cohort. How strong? How rare?

 ?         Despite this catalogue of drawbacks and “softness”  -  or complete absence  -  of data, the authors then go on to claim that they have been “unable to demonstrate a correlation between secular trends in early childhood MMR immunisation coverage and autism caseload”. A dispassionate and objective observer would find this wholly unsurprising.

 ?         The assumption that there would be a plateau in the increase in MMR (to match a plateau in take-up of MMR) would only be valid if the background susceptibility of the infant population has remained constant. If successive generations of children became increasingly susceptible to an adverse event such as autism, caused by MMR, then this might well be reflected in a continuing rise in autism. This obvious possibility is not addressed. It does not have to be the case that the relationship between MMR and autism is a simple linear one, without other factors being involved.

 

Overall verdict: this study is not relevant to disproving an MMR/autism link If the study does have a value, it is to demonstrate that extremely weak studies are not only capable of achieving publication  -  apparently without attracting peer-review criticism  -  but also that they are then uncritically welcomed, and publicised, by one side of the argument. This in itself is illuminating.

 

67.      Paper by DeWilde, Carey, Richards et al, Do Children Who Become Autistic Consult More Often After MMR Vaccination, British Journal of General Practice, March 2001

 

This paper appeared in the British Journal of General Practice, March 2001. It attempted to test the hypothesis that a degeneration into autism, with subsequent diagnosis, would be reflected in increased consultations with the child’s general practitioner.

 

This would appear to be an extremely weak hypothesis to test. For example:

 

?         It may be difficult to place a definite date upon degeneration

 ?         Parents may not seek assistance from their GP immediately, or even at all in some cases

 ?         Parents may seek advice from health visitors or other health professionals

 ?         Parents may see a GP only once, to obtain a referral to a specialist paediatrician

 ?         Parents may see their GP for reasons unconnected with autism, confusing the data in some cases

 ?         Parent may be extremely reluctant to see their GP, because of the sometimes extreme practical difficulties of taking an autistic child to a public surgery, with waits etc.

 

The study authors do not acknowledge any of these serious potential methodological flaws, nor do they attempt to quantify them in an attempt to validate the effectiveness of their methodology.

 

The authors looked at only 71 cases of autism, a small sample by any standard for testing a statistical hypothesis, and identified numbers of consultations from a primary health care database. It found that there was no significant difference between cases and controls for numbers of consultations in either the six months before/after immunisation, or the two months before/after immunisation.

 

The study also noted

 

?         that there was a significant fall-off in consultations in the six months after immunisation, in both cases and controls. However, it did not address the possibility that this might have been for two entirely different reasons, with healthy children not needing to be taken to their GP, and autistic children not being seen by their GP for other reasons such as those set out earlier. The study simply assumed that the fall-off in the cases and the control group was for the same reason, without evidence to underpin this assumption.

 ?         It acknowledged that it could be criticised because the study authors “cannot confirm that our cases truly suffer from autism

 ?         The study, like almost all other studies that “prove” no MMR/autism link, did not specifically address the cohort of children alleged to have degenerated as a consequence of MMR, and who are now proceeding through the legal processes

 ?         It acknowledged that “some diagnoses will have been missed

 ?         It admitted that “it seems unlikely (my emphasis) that these will be specifically those associated with MMR”, although it offers no evidence to support this assumption.

 ?         The study notes that “”the clear difference in consultations in the six months before the diagnosis of autism” (between cases and controls) “emphasises that consultations were being recorded and that differences in consultation rates between cases and controls were detectable”. But the study does not address the possibility that the higher frequency of consultations by cases is linked to a potentially-associated condition, such as otitis media (and consequent antibiotic use), and that cases moved from more frequent consultations than controls for such a condition, to more frequent consultations than controls for a wholly different and more serious condition.

 

Overall verdict: this study is not relevant to disproving an MMR/autism link. In short, there are so many caveats, acknowledged and unacknowledged shortcomings and other methodological limitations to this study that its conclusions are virtually valueless. Again, it is illuminating that it has been so well received by one side of the debate (the UK Department of Health).

 

68.     Study by Davis et al, Measles-Mumps-Rubella and Other Measles-Containing Vaccines Do Not Increase the Risk of Inflammatory Bowel Disease, Archives of Pediatrics and Adolescent Medicine, 2001, 155: 354-359

 

This study was conducted in the US on the populations of four health maintenance organisations as part of a vaccine safety programme co-ordinated by the Centres for Disease Control and Prevention.

 

The study focussed on the following questions:

 ?         Was the age of first vaccination with MMR or other measles-containing vaccine, or receipt of vaccination itself, associated with an increased risk for Crohn’s disease or ulcerative colitis later in life?

 ?         Was receipt of MMR or other MCV associated with the acute onset of disease shortly following vaccination?

 

In each of the areas, trained staff reviewed medical records. Cases were of individuals enrolled since birth (some as early as 1958) to 1989. It was claimed that consistent criteria were used for definite and probable diagnosis of Crohn’s disease, ulcerative colitis or unspecified irritable bowel disease. This involved diagnosis by a gastroenterologist, “with signs and symptoms and a diagnostic test for IBD”. Five controls were selected for each case, matched by sex, health organisation and year of birth. Dates of vaccination, type of vaccine and date of diagnosis were also recorded.

 

There were 155 cases of IBD with 152 definite or probable cases. Seven had no discernible onset, two were of “unspecified disease” and one was vaccinated when older than 10 years. This left 142 cases and 432 controls for further analysis.

 

The study found that:

 

?         the risk of inflammatory bowel disease was the same whether for vaccinated or unvaccinated people

 ?         there was an average of 140 months between vaccination and diagnosis for cases.

 ?         Only 1% of cases developed inflammatory bowel disease within a year of vaccination

 ?         Only 1% of controls developed inflammatory bowel disease within a year of vaccination.

 ?         Whether children were vaccinated before 12 months, between 12 and 18 months, or after 18 months, showed no difference in the risk of developing inflammatory bowel disease

 

However, the study team had to acknowledge several serious limitations to this study:

 

?         Only patients with a physician diagnosis (usually a gastroenterologist) were included. This could have potentially missed many cases, particularly if those missed were of an insidious new variant

 ?         The team acknowledged the inherent limitations of diagnostic accuracy in any retrospective study

 ?         They had little information on children or adults with non-specific colitis that did not lead to an eventual diagnosis of IBD  -  surely a key failure, given the nature of the research by the Wakefield team at the Royal Free Hospital in London

 ?         There was an acknowledged limitation over statistical power. The report admitted:: “We were able to effectively rule out associations larger than 2-fold between ever being vaccinated with MMR and developing IBD, and associations larger than 3-fold between vaccination with other measles-containing vaccines and IBD. However, we had a limited sample size from which to look at the independent associations between vaccination and either Crohn’s disease or ulcerative colitis, or at the relationship between timing of vaccination early in life and subsequent risk for Crohn’s disease or UC.” This seems to be a serious self-criticism, yet oddly it does not seem to have had much effect on the study’s assertive conclusions.

 

The study’s reliance on patient records should also be questioned. The analysis of records can by definition be only as good as those records themselves. No study (as far as is known) has yet endeavoured to verify whether children suffering from acquired autism, ileal lymphoid nodular hyperplasia or non-specific colitis have medical records that accurately reflect these conditions. There are grounds for suspecting that the very reverse may be the case. The difficulties in obtaining a clear and timely diagnosis of autism are well known. The nature of the autism problem, with many patients without speech, means that the precise nature of the patient’s complaints and symptoms may be poorly recognised, and even more poorly recorded.

 

Overall verdict: although this study at first sight appears more persuasive than some others, it too fails to provide convincing evidence against an MMR/autism link. The study may be seriously flawed due to its retrospective nature, when the condition in question (acquired autism after MMR/MCV) has only recently received publicity, and because of doubt over records.

 

69.     Further Paper by Farrington, Miller and Taylor, MMR and Autism: Further Evidence Against a Causal Association, Vaccine, 19 (2001) 3632-3635

 

When it became apparent to Taylor, Miller and Farrington that the time-lapse for degeneration into autism might be a protracted one, they were obliged to re-analyse their earlier data.

 

?         Farrington, Miller et al repeated their view of the original Wakefield study, that it was very small (12 children) and that the interval between receipt of MMR and first behavioural symptoms varied from 24 hours to two months. However, the Wakefield study cohort subsequently grew to about 200, and this has not been acknowledged by Farrington, Miller et al in this further paper.

 ?         The Farrington, Miller et al study also has not taken account of the Spitzer, Aitken et al study and its implications (see later sections). They also maintain that they “found no evidence to support a causal association”. But they themselves, in their first study, unconvincingly dismissed a clustering of parental concerns at around six months. They maintain this unconvincing stance.

 ?         Farrington et al concluded that the temporal association found by Wakefield et al was “a combination of selection bias and chance”. This latter is a highly contentious conclusion, suggestive of wishful thinking, in the same way as the dismissal of the six-month clustering was.

 ?         In this second paper, the authors seek to re-test their earlier conclusions by removing any preconceived fixed-time interval between vaccination and the onset of autism. Again, they use a statistical methodology, self-matched case-series analysis, but once again with a very small (for this method) data set of just 64 cases of what they describe as “unvaccinated” children with autism  -  presumably, they mean “unvaccinated with MMR”  -  plus 231 cases of children with autism who had received one dose of MMR, and a further 62 cases of children who had received two doses of MMR (total 357 children).

 

The study found that:

 ?         for the 357 cases, the observation periods had a median of 89 months, a maximum of 191 months.

 ?         The oldest age at diagnosis was 180 months.

 ?         Some 64 did not receive MMR.

 ?         Some 43 received MMR after age 2 years, at median age 57 months, maximum 165 months.

 ?         Some 62 cases received a second dose of MMR, at median age 54 months, maximum 159 months.

 

The comparison of relative incidence for each group finds that there is little difference between those that had received MMR and those previously referred to as “unvaccinated”, but which seems to have really meant “vaccinated with single-antigen measles vaccine”  -  the paper is not clear.

 

The major criticism of the earlier paper using this data (see above section) were that there was only a proxy for “onset of autism” (a questionable term in itself). The original study measured diagnosis, parental concern and regression (if applicable) from medical records. But these would be variably delayed from any actual “onset event”. The very poor correlation between these proxies and the “event” means that the analysis loses all statistical power.

 

Major criticisms of this further re-worked paper’s statistical methodology are that:

 ?         Regarding the whole period following MMR as being “at risk” is questionable.

 ?         Looking to see if those who have MMR earlier have a proxy variable earlier is erroneous, when one observes the very narrow timescale for the application of MMR in this paper. When the input signal (the age of receipt of MMR) has very little variability, one would be unlikely to find this reflected in the output signal (date of diagnosis)

 ?         The above flaw means that the only statistical power left is coming from finding any difference between those who have MMR and those who have not. But most of those who do not have MMR are those older children who are of the pre-MMR generation. So Farrington et al’s analysis is effectively asking whether those who are older had had an earlier or later onset of autism (as measured by the proxy variables).

 

Overall verdict: this study fails to provide any convincing evidence against an MMR/autism link.

 

(Note: this study has been claimed by the UK Medical Research Council to represent “strong positive evidence” of there being no MMR/autism link)

 

70.     Paper by Fombonne & Chakrabarti, No Evidence for a New Variant of Measles-Mumps-Rubella-Induced Autism, Pediatrics, Vol. 108 No. 4 October 2001

 

This paper examined whether there is a new phenotype of autism involving regression and gastrointestinal symptoms.

 

It is suggested that where this paper is flawed is in the assumptions underpinning the hypotheses that are tested. All else stems from that. Fombonne & Chakrabarti assume that if autistic enterocolitis existed, then one or more of the following six predictions should be supported by empirical data:

 

?         Prediction (1)  -  “childhood disintegrative disorder has become more frequent”. (The study found the prevalence of childhood disintegrative disorder to be 0.6/10,000, or 1 in 16,666. But this seems far too low in comparison with other recent studies).

 Comment  -  historic data is not available to prove this either way. The claim that the present rate of 1 in 16,666 represents no increase is further undermined by its non-credible low level. Other studies have found rates very many times higher. This strongly suggests that the study is flawed.

 ?         Prediction (2)  -  “the mean age of first parental concern for autistic children who are exposed to MMR is closer to the mean immunisation age than in children who are not exposed to MMR.”

 

Comment  -  the study found that there was no difference in the mean age at first parental concern between the two samples exposed to MMR (19.3 months and 19.2 months) and the pre-MMR sample (19.5 months). But no argument has been presented as to why there should be a difference. A difference might be expected, but its absence in itself does not prove anything. It is perfectly possible that childhood disintegrative disorder has several causes, and that the arresting of development could be noticed at around the same time. Pre-MMR children who became autistic may well have become so due to an adverse outcome from monovalent measles vaccine. This possibility does not seem to have occurred to Fombonne. There is also a simplistic focus upon MMR alone as a sole factor, working in isolation, rather than as part of a complex process.

 

?         Prediction (3)  -  “regression in the development of children with autism has become more common in MMR-vaccinated children.” The study found that the rate of developmental regression reported in the post-MMR sample (15.6%) was not different from that in the pre-MMR sample (18.4%) and therefore there was no suggestion that regression in the development course of autism had increased in frequency since MMR was introduced. The study also found that in the epidemiologic sample, the subset of autistic children with regression had no other developmental or clinical characteristics, which would have argued for a specific etiologically distinct phenotype.

 

Comment  -  the samples were small. The study used three samples, a post-MMR sample of 96 children with PDD, a pre-MMR sample of 98 autistic patients, and a post-MMR sample of 68 autistic patients. These are very small numbers to use in a statistically-based study. Fombonne and Chakrabarti’s results should thus be treated with caution, as a few cases either way would impact upon their conclusions.

 

?         Prediction (4)  -  “the age of onset for autistic children with regression clusters around the MMR immunisation date and is different from that of autistic children”. The study found that parents of autistic children with developmental regression detected the first symptoms at a very similar age (19.8 months) to those of autistic children without regression (19.3 months). The study also found that the mean intervals from MMR immunisation to parental recognition of autistic symptoms were comparable in autistic children with or without regression (248 days vs 272 days, not significant).

 

Comment  -  but regression might not necessarily be expected to “cluster round”, but may follow MMR at a delay of weeks, months or years. There is no scientific justification for assuming that children with regression after MMR should have their condition recognised at a different time to those who did not regress after MMR. In any event, it is stated that the difference between 248 days and 272 days is not significant, but it is almost 10% different, and this difference has not been explained.

 ?         Prediction (5)  -  “children with regressive autism have distinct symptoms and severity profiles.”

 Comment  -  little scientific justification for testing this assumption is given in the study, which also refers to external features such as behaviour, when the real focus of interest should be on gut biopsies and ileocolonoscopies of the actual children, which of course were not done in this study. Not enough is known about autistic enterocolitis to make such an assumption about external characteristics into a key test.

 

?         Prediction (6)  -  “regressive autism is associated with gastrointestinal symptoms and/or inflammatory bowel disorder”.

 Comment  -  but the children in this study did not undergo ileocolonoscopy. Their condition was medically unresearched.

 Other comments: 

 ?         this is a statistical analysis of random groups of children, not of the children whose cases are going to the High Court. The numbers are extremely small, too small for a reliable interpretation to be made

 ?         The assumption seems to have been made that children could not have been damaged by vaccines other than MMR. The Lassiter court case outcome (US) means that there is evidence, that has been accepted in a Court that other multiple vaccines also trigger autism.

 ?         What this study set out to do was not to investigate the cause(s) of damage to specific children, but to clear MMR of any complicity. At first sight, it succeeds in the latter, but at closer analysis, it makes numerous unfounded assumptions that considerably weaken the strength of its conclusions. At worst, it demonstrates the central flaw of designing a study hoping to achieve a desired outcome, rather than to investigate a problem.

 

Overall verdict: this study fails to provide any convincing evidence against an MMR/autism link.

 

(Note: this study has been claimed by the UK Medical Research Council to represent “strong positive evidence” of there being no MMR/autism link)

 

71.     Paper by Taylor, Miller et al, Measles Mumps and Rubella Vaccination & Bowel Problems or Developmental Regression in Children with Autism: Population Study, published BMJ.Com, 8th February 2002

 

The objective of this paper was to investigate whether MMR vaccination was associated with bowel problems and developmental regression in children with autism, and to look for a “new variant” form of autism.

 

Some 278 children with what the authors defined as “core autism”, and a further 195 with “atypical autism” were studied. These were identified from disability registers. The children were born 1979-1998.

 

The outcome measures that were studied were:

 

?         Recorded bowel problems lasting at least three months

 ?         Age of reported regression (where it was a feature)

 ?         Relation of these to MMR

 

Of the 473 children whose records were reviewed, 81 (17%) were reported to have associated bowel problems, comprising:

 

?         42 with constipation

 ?         7 with constipation and diarrhoea

 ?         19 with diarrhoea

 ?         7 with food allergy

 ?         2 with non-specific colitis with ileal-lymphoid nodular hyperplasia

 ?         (4 noted as “others”)

 

The study reported that:

 

?         The proportion of children with developmental regression (25% of the overall) or bowel symptoms (17%) did not change significantly during the 20 years from 1979 (MMR being introduced in October 1988)

 ?         No significant difference was found in rates of bowel problems or regression in children who received the MMR vaccine before their parents became concerned about their development, compared with those who received it only after such concern, and those who had not received MMR.

 ?         A possible association between non-specific bowel problems and regression in children with autism was seen, but this was unrelated to MMR

 ?         The study concluded that its findings provided no support for an MMR-associated “new variant” autism, and further evidence against involvement of MMR

 

The study admitted that it had the “strengths and weaknesses of data based on case notes. Data was not recorded systematically and there was variability in the level of detail.”

 

Comment  -  there are several major criticisms that can be made of this study.

 

?         Most importantly, it was an epidemiological study of case notes, not a clinical study (with examination and clinical analysis of samples) of the cohort of children believed to have been damaged.

 ?         No clinical examination appears to have been undertaken by the study team, and it is highly questionable whether such examination or analysis was ever undertaken in the past by paediatricians or specialists in the field, either. This greatly reduces the value of this study.

 ?         Equally importantly, the study relies heavily upon the accuracy of child health records. Experience suggests that the health records of autistic children do not accurately reflect their condition, with numerous specialists and agencies involved and with the records not necessarily accurately reflecting the information supplied by parents, due to poor reporting, poor recording and undervaluing of parental “anecdotal” evidence.

 ?         For health records to be relevant to an assessment of a novel syndrome, which was first only widely reported in 1998 (and has been repeatedly denied by the Department of Health ever since), health professionals would have to connect what the parents were reporting, and the condition of the children, with the new syndrome. They would also then have to have commissioned appropriate clinical examination of the children, and ensured that this was accurately recorded.

 ?         It is patently obvious that this would not have happened for the perhaps the first nineteen of the twenty years 1979-1999. The study is therefore trying to assess records made in an era before in-the-field awareness existed, and in all probability without any appropriate clinical examination or analysis ever having taken place in the past, as well as during the study.

 

These major criticisms would appear to leave the study seriously lacking relevance. Despite this, the study was described by the Department of Health as “elegant”.

 

The independence of the study also must be questioned.

 

Dr. Elizabeth Miller, head of the Immunisation Division of the Government’s Public Health Laboratory Service, was a direct participant at the Department of Health’s re-launching of the MMR programme in January 2001, and thus cannot be regarded as a detached “outside” researcher.

 

And as long ago as December 1997, Professor Brent Taylor described Dr. Andrew Wakefield, in writing, as “a zealot.....who thinks that MMR is the cause of all the problems of the Western world.” This suggests that Taylor’s stance towards the alleged MMR/autism issue was set several years ago. Researchers are entitled to their views, but, if these are expressed in such a highly charged manner, then it is only right that such prior remarks should be set alongside their study findings, particularly when such findings are regarded, and publicised, by Government as an “independent” study.

 

There are other serious methodological criticisms of this latest Taylor, Miller study:

 

?         The study looks at percentages of autistic children, giving the impression that background rates of autism aren’t increasing. What the study findings should also include is a plot of the actual numbers of cases diagnosed per year, and of inflammatory bowel disease/other aspects. This is a crucial omission. It is impossible from the study report to tell whether these numbers (as opposed to percentages) have changed over time.

 ?         The study does not reveal the sample sizes for each year. How many children fall in each year is not shown. It also therefore does not confirm whether the distribution is even, across the years. This makes the data impenetrable to outside scrutiny. (Note: on ITV’s “Dimbleby” discussion programme on 10th February, Prof. Taylor was challenged by the National Autistic Society to release his raw data for independent analysis, and declined to do so).

 ?         Following on from the above, any logistic regression on year of birth is going to be highly underpowered as a way of detecting any MMR effect.

 ?         The study does not make clear exactly how many of the 473 had MMR how many times, and precisely when. This is a fundamental failure in methodology.

 ?         Notably, the study does not take the most obvious route of all, of comparing a large group of MMR-vaccinated children (10,000+) with another large group (10,000+) of unvaccinated children. An epidemiological study could have been undertaken of such groups. A study of only 473 children is far too small to detect relatively-rare adverse outcomes. The study size is so small that in some years there may have been no more than a handful of children.

 

(Note: the study by Wakefield O’Leary et al looked at about 200 children, but this was a clinical study, not an epidemiological study. A cohort of 200 children in a clinical study is vastly more reliable than a cohort of 473 children in an epidemiological study). 

 

?         As only 17% of the sample had “not had” MMR, and only 18% had “reported bowel problems”, this means that the study inevitably is not very powerful.

 ?         According to Taylor Miller et al, their study identified just two children with ileal-lymphoid nodular hyperplasia, the novel syndrome being studied by Wakefield et al. This is either wholly inadequate because it is such a tiny sample, or it alternatively suggests that the case-notes missed many cases amongst the remaining 473 cases. It would be extremely surprising if the ILNH condition being studied by Wakefield only occurred in 2/473 children. What this suggests is that very few children out of the 473 have been clinically investigated to ascertain whether or not they have ILNH.

 

?         The cohort of children identified by the study as having “bowel problems lasting three months” is highly unspecific and vague. Records would be most unlikely to accurately reflect the extent, intensity, nature or length of time these “problems” consisted of.

 ?         The percentage of “regressing” children is identified as being 25%, yet Simon Baron-Cohen’s CHAT system uses a rigorous definition which gives a rate of 10%. This difference suggests that the Taylor Miller definition may have been unusually wide

 ?         “Parental concern” is not defined. It is not clear whether this equates to a visit to the GP, or to personal parental doubt. It is unlikely that health records would accurately reflect this, particularly if onset was insidious.

 ?         Perhaps the most interesting finding is that there is a reported highly significant association between developmental regression and bowel problems. But as 87% had MMR, and only 31 had bowel problems, one might expect 27/31 of those with bowel problems to have had MMR, and 4/31 to have not had MMR. This again has very little statistical power, because the numbers are so very small as to be capable of being influenced by pure chance, in addition to other methodological flaws described elsewhere such as poor or inaccurate records.

 ?         It is also not clear which children that had “had MMR”, also had the booster as well as the early immunisation, the booster but not the early immunisation, or the early immunisation but not the booster.

 

In subsequent British Medical Journal correspondence, the paper was also heavily criticised over its statistical methodology and the refusal to release raw data. These criticisms were by Aubrey Blumsohn, a Senior Lecturer at the University of Sheffield, UK. His main points were that the authors provided no statistical confidence limits in relation to several key findings

 

The most extraordinary feature of this inconclusive study was the way it was hailed as providing “conclusive” irrefutable evidence that there was no link, despite is many serious drawbacks. Its publication was met with a further claim by the Scottish chief medical officer, Dr. Mac Armstrong, that any calls to mount clinical studies into the MMR/gut/autism issue would be “resisted”. This line of argument was repeated in a UK television interview by Dr. Elizabeth Miller on 13th February 2002.

 

Conclusion: this study offers no evidence against an MMR/autism link.

 

(Note: this study has been claimed by the UK Medical Research Council to represent “strong positive evidence” of there being no MMR/autism link)

 

72.     Review by Donald and Muthu, Bazian Limited, London UK, published in the British Medical Journal, June 2002

 

This was not a new study, but a review of existing studies. It claimed that it followed the most in-depth analysis of the scientific literature to date, looking at 2,000 existing studies and papers, and offered clear reassurance for parents. However, only 36 studies were actually cited, the remainder having apparently been disregarded on the basis of self-imposed restrictive criteria for inclusion in the review.

 

The study found:

 ?     no evidence of an MMR/autism link.

 ?              strong evidence that both MMR and single measles vaccination virtually eliminated risk of measles and measles complication

 ?              Consistent evidence that MMR and single measles vaccines are associated with small similar risks of self-limiting fever within three weeks of vaccination

 Comment:  there are a number of fundamental (and severe) criticisms that can be made of this review’s methodology:

 ?             The study was only a review. It offered no fresh evidence.

?             It was not a clinical study. It did not examine any children.

 ?             As the syndrome of autistic enterocolitis is a novel one, it is unsurprising that a review of past literature would not find evidence of an MMR/autism link. In the main, such studies have neither been undertaken nor reported. If you look into an box that is known to be empty, you should not be surprised at finding nothing.

?             The review effectively asks the wrong question, “Is MMR safe?”, whereas the fundamental questions should be “What is wrong with these specific children, what are the features of their condition, and what damaged these specific children?”.

?             Absence of evidence is not evidence of absence

?              The study deduced that, because there had not been a “stepwise” increase in autism following MMR’s introduction, there could not be an MMR/autism link. However, this does not take account of delays in diagnosis, differential risk in relation to different strains of MMR and the withdrawal of two brands in 1992 due to side-effects.

 

The study (inexplicably) took only the February 1998 paper by Wakefield et al as being the published evidence for any MMR/autism link, and appeared to disregard a considerable number of subsequent papers (all of which are reviewed later in this Briefing Note).

 

In effect, all the study could reasonably have concluded is that there is a lack of published research that is relevant to the question. However, the researchers claimed that their paper should signal the end of the MMR/autism debate. Dr. Donald appeared on BBC Radio 4’s Today programme and stated that “It was time for the parents to stop chasing shadows” (re MMR).

 

Conclusion:  this review offers no hard evidence whatever against the possibility of an MMR/autism link.

 

73     Study into Relationship Between Childhood Gastrointestinal Disorders and Autism: Nested Case-Control Study Using Data from the UK General Practice Research Database, British Medical Journal Volume 325, pp 419-421, Boston University (researchers’ details not known), August 2002

 

This study identified 96 children with autism from the UK General Practice Research Database between 1988 and 1999 (MMR was introduced into the UK in October 1987). Each case was matched with up to five controls without autism. The study considered the time relation between MMR vaccination and the onset of gastrointestinal symptoms among the cases. Findings were:

 ?              No increase in a history of gastrointestinal disorders, coeliac disease, food intolerance or recurrent gastrointestinal symptoms among children with autism compared with normal controls

 ?              No temporal association between MMR vaccination and the onset of gastrointestinal symptoms in children with autism

 

The authors acknowledged that they could not exclude the possibility that some children in the study had sub-clinical gastrointestinal symptoms before their presentation with autistic behaviour. However, they commented that the children described by Wakefield and colleagues had symptomatic gastrointestinal disease.

 

The authors also could not exclude the possibility that severe gastrointestinal disease might be associated with the development of autism in certain individuals. However, they thought that this was likely to be uncommon.

 

Comment: the authors themselves acknowledge the shortcomings of their methodology. Further criticisms are that child health records are unlikely to fully reflect a novel gastrointestinal condition that is subtly different to Crohn’s Disease or ulcerative colitis. No children were examined. The study apparently failed to distinguish between late-onset regressive-type autism and autism from infancy or birth.

 

Conclusion: this study does not disprove a link between MMR and certain sub-types of autism.

 

74.     Study by Madsen, Hviid, Vestergaard, Schendel, Wohlfarht, Thorsen, Olsen and Melbye, A Population-Based Study of Measles-Mumps Rubella Vaccination and Autism, New England Journal of Medicine, November 2002, 347: 1478-1482.

 

This study paper, again, not to be confused with the Pediatrics paper reviewed above, also attracted a great deal of attention, largely uncritical, when it was published towards the end of 2002, mainly because of its claimed size and, of course, its conclusion that there was no evidence of any MMR/autism link. The paper featured:

 ?              A retrospective cohort study of all children born in Denmark from January 1991 through till December 1998

 ?              MMR vaccination data obtained from the Danish National Board of Health. Information on the children’s autism status was obtained from the Danish Psychiatric Central Register, which contains information on all diagnoses received by patients in psychiatric hospitals and outpatient clinics in Denmark

 ?              Of the 537,000 children in the cohort, 441,000 had received MMR. The study identified 316 children with a diagnosis of autistic disorder and a further 442 with a diagnosis of other autistic-spectrum disorder (total 758). (Note: 758 cases amongst 537,000 children represents a rate of 1 in 709, or 14 per 10,000).

 ?              After comparing autism amongst vaccinated and unvaccinated children, the study concluded that there was no association between the age at the time of vaccination, the time since vaccination, or the date of vaccination and the development of autistic disorder.

 

After initial uncritical review by the press, this study received a very thorough analysis by the parents, notably Dawn Richardson of the US parents’ group PROVE and Sally Bernard of the group Safe Minds. Richardson’s and Bernard’s key criticisms were:

 ?              One of the omissions of the study was its failure to consider the thiomersal issue. The parents’ view as at the end of 2002 was that the thiomersal aspect and the MMR aspect were interlinked in the pathogenesis of autism. Press reports confirmed that thiomersal was removed from Denmark’s vaccines prior to the birth-dates of the children in the study cohorts. It therefore remains unstudied as to whether a child’s immune response, inhibited by elevated mercury levels from thiomersal, has a lessened ability to respond to the measles virus in MMR. The Madsen study does nothing to address this.

 ?              The Madsen study only focussed on MMR and not other vaccines implicated in autism

 ?              The study (as noted elsewhere) failed to distinguish between different types of autism

 ?              An epidemiological study of this scale would be unable to detect a potential connection between the persistence of measles virus in susceptible children and autism. The number of regressive-autism cases (out of 758) would be too small to give statistical power to any conclusions (note: in an epidemiological study, large numbers are needed. This criticism would not apply to a clinical study, such as conducted by Wakefield when at the Royal Free Hospital).

 ?              The Madsen study paradoxically appears to imply support for a thiomersal role, since it suggests that autism in Denmark is at a much lower rate of incidence than in the US or UK

 ?              Only psychiatric records were assessed  -  not medical records. There was no data on gastrointestinal symptoms. No cerebral spinal fluid or gastrointestinal samples were taken or analysed.

 ?              The study covered eight birth cohorts, but two of these, born in 1997 and 1998, were only one or two years old when the data records were obtained by the study at the end of 1999. These age groups are too young in most cases to either have a diagnosis of autism or (probably) to have received MMR. Therefore, in these two cohorts, true autism rates will be underestimated, and vaccination rates over-estimated.

 ?              Children who were in fact vaccinated were assigned to the unvaccinated group if they were diagnosed with autism before they had received MMR. This blurs the distinction between vaccinated and unvaccinated groups. It is not clear what effect this would have on the results.

 ?              A number of the measures used to arrive at the conclusion that autism/ASD disorders were not associated with MMR are irrelevant, including age at vaccination with MMR, time interval between receipt of MMR and diagnosis of autism, and year of MMR vaccination.

?              As the authors themselves acknowledge (page 1481), they had no information on the presence or absence of any family history of autism. There was considerable publicity in Denmark in 1993 on MMR/autism linkages. It is quite possible that those families with a history of autism went on to avoid MMR, undermining the study findings.

?              The decision by the study team to register as autistic cases only those children who only met two strict diagnostic criteria could have meant that many affected children would have been excluded

?              The study does show that MMR is not the cause of all autism  -  but no-one has ever suggested that it was.

?              The study did not, of course, involve the clinical examination of any children or the analysis of samples.

 

The study was also questioned in a letter to the New England Journal of Medicine (6/3-06 issue) by Professor Walter Spitzer of McGill University, Montreal, as follows:

 

?              The study has some methodologic problems. A review of the clinical records for only 40 of the 316 children with autistic disorder is inadequate

?              Without a multidisciplinary review of lifetime records, important errors would have been unavoidable

?              Although it would be difficult, with the use of clinical criteria one could identify subgroups among most of the children, notably subgroups with regression

?              The power of the study was high, but misleading.......(potentially) masking the (MMR) association in a small sub-group

 

The study was also criticised in the same publication by Dr. Michael Mullins of Washington University School of Medicine, St. Louis:

 

?              (the study) has multiple flaws that compound the bias toward a finding of no association. First the use of person-years instead of persons magnifies the weight of the early cases (when the prevalence of autism was relatively low) and minimizes the weight of the later cases (when the prevalence was five times that in the early period).

?              Secondly, mean ages at diagnosis were 51 months for autism and 63 months  for other autistic-spectrum disorders. A child born early in the study period had a higher likelihood of receiving a diagnosis than a child born later in the study period

?              Thirdly, children in the unvaccinated group underwent a mean of 5.0 years of follow-up (482,360 person-years for 96,648 persons), as compared with 3.7 years in the vaccinated group (1,647,504 person-years for 440,655 persons). This discrepancy also reduced the likelihood that autism would be detected in a vaccinated child as compared with an unvaccinated child.

?              The authors overstate their conclusion in the abstract by saying “this study provides strong evidence against the hypothesis that MMR vaccination causes autism”. Even if the study did not suffer from these flaws, the strongest defensible conclusion would be that the study did not detect an association between MMR and autism.

 

Madsen responded to these published comments by admitting:

 

?              We cannot rule out the possibility that at least one child would not have become autistic if he or she had not been vaccinated

?              we can say that MMR vaccination is not the explanation for an increasing incidence in autism

?              we can say that MMR vaccination is not one of the common causes of autism. But we cannot prove anything......

?              We do not claim to have proven that MMR vaccination can never cause autism

?              We cannot rule out the existence of a susceptible subgroup with an increased risk of autism if vaccinated, but such a subgroup must be small

 

The researchers, in a press comment, admitted that they did find a dramatic increase in the number of diagnosed cases of ASD during the study period. “No one knows why this increase is taking place.....the study was not designed to answer that question.....”

 

Comment: there are clearly many shortcomings to this study. No child was evaluated for immune system dysfunction, inflammatory bowel disease or the presence of measles RNA in their blood, intestines or cerebral spinal fluid.

 

75.     Study, Mercury Concentrations and Metabolism in Infants Receiving Vaccines Containing Thiomersal  -  A Descriptive Study, by Pichichero, Cernichiari, Lopreiato and Treanor, University of Rochester Medical Center, US, published in The Lancet, November 30th 2002.

 

This was a study published in The Lancet, conducted by Michael Pichichero and colleagues. Its appearance was hailed with relief by the medical community as “proof” that there was not a potential thiomersal role in the vaccine/autism debate, and that thiomersal-containing vaccines were safe.

 

Dr. Pichichero was interviewed by Dr. Laurie Barclay for Medscape. He summarised his study as follows:

 ?              We looked at the blood levels of mercury in children who received thiomersal-containing vaccines. Not a single child had a blood mercury level approaching the lower safety limit established by the US Environmental Protection Agency

 ?              Former predictions of possible paediatric problems with mercury in vaccines, which led to the removal of thiomersal from US vaccines (comment  -  it was only phased out, not removed, and other countries, eg the UK, did not even phase it out), were based on the notion that metabolism of ethyl mercury in the vaccine was the same as that of methyl mercury in fish. But our (the Pichichero) study showed that elimination (from the body) of ethyl mercury from vaccines was about six times as fast as that of methylmercury. The rapid metabolism was thought to “probably” account for the very low blood levels in the children studied

 ?              The study accounted for virtually all the mercury contained in the vaccines in the stools of the children, with not much excretion in the urine, so there was “really no evidence” that there was any mercury unaccounted for which could be accumulating in the bones or elsewhere. (However, Pichichero then admitted that the study “was not a toxicity study and so did not examine this issue directly”).

 

Asked if there were any study limitations, Pichichero responded that this was a small study of 61 children, comprising 20 two month olds who received thiomersal, 20 six month olds who got thiomersal, and 21 controls. He explained that because the study had not anticipated the rapid clearance of ethylmercury with a half-life of only 6-7 days, the study had predicted the sampling times on the basis of an assumed 45-day half-life. (Comment  -  but this doesn’t address the drawback that the study was only small).

 

Asked about the basis of the EPA’s public safety limits for mercury levels, Pichichero responded that the EPA levels were based on studies in the Faroes which had looked at the toxicity of methyl mercury ingestion from whalemeat. Mild neurological problems had occurred at levels in the blood of 200-300 ng/mL, and the mildest detectable neurodevelopmental toxicity had occurred at levels of 58ng/mL. The EPA had therefore added in a safety factor of ten, and taken the view that levels should not exceed 5.8ng/mL to be totally safe.

 

In the Pichichero study, most children had had levels of 1 to 2ng/mL, and two had had 2-3ng/mL. One child had had 4ng/mL. No child had approached the 5.8ng/mL EPA limit. (Comment: isn’t a level of 4ng/mL “approaching” the 5.8ng/mL level?  -  it is almost 70% of it. And remember, this was a very small study indeed. What if they had measured levels in 1,000 children. Mightn’t that have produced a few examples well in excess of the EPA limit?).

 

  Pichichero also made three other revealing statements:

  *    “Our findings were (also) pivotal in the World Health Organisation’s recommendation that thiomersal will remain in all vaccines provided by them to other countries”, and

  *     (in answer to the question, “What are the advantages of using thiomersal in vaccines”, he responded “Cost is a major issue. If you don’t use preservatives at all, you have to dispense vaccines in single-dose vials, which is not only more expensive but which may lead to more errors in administration”, and

  *     “The potential toxicity of using newer (non-thiomersal) preservatives is unknown, so we are trading the very small known risk (his words) of thiomersal for an unknown one”. (Comment:  why does Pichichero imply the assumption that the “unknown” risks of other vaccines would be higher?)

 

The study was critically reviewed by Sally Bernard of the US parents’ group Safe Minds. Bernard’s comments were as follows:

 

?              The article and accompanying commentary made a number of sweeping statements about thiomersal’s safety. The design and results of the study did not support these statements.

 ?              Pichichero has acknowledged financial links with Eli Lilly & Company, the developers of thiomersal and the main target (to date) of US autism litigation. In an article back in April 2000 in the American Academy of Family Physicians newsletter, Dr. Pichichero made the following disclosures of interest: he had received research grants from Abbott Laboratories, Bristol-Myers Sqibb Company, Eli Lilly (note), Merck, Pasteur Merieux Connaught, Pfizer Laboratories, Roche Laboratories, Roussel-Uclaf, Schering Corporation, SmithKline Beecham, Upjohn, and Wyeth-Lederle.

 ?              Pichichero’s earlier work has been cited in at least 21 vaccine patent applications. Many of his previous published papers deal with vaccines containing thiomersal. The University of Rochester (US) website describes him as an immunologist.

 ?              The sample size of the Pichichero et al Lancet study was very small. Only 33 children were used for the blood mercury assessment work that the study conclusions hinged upon. The small sample means that the study lacks statistical power.

 ?     The study sample was not drawn at random, but reflected convenience.

 ?              Given that the half-life of ethylmercury appears to be 6 to 7 days, virtually all (if not all) blood samples drawn would have missed the peak blood concentrations of mercury

 ?              It is impossible to state what the peak values actually were, as they were not measured. It was also impossible to calculate average blood concentrations unless the peak concentrations were accurately measured.

 ?              Sally Bernard argues that it is disingenuous to compare the blood levels in this study with past methylmercury levels without using any adjustment factor, because the latter incorporated peak levels into their values, whereas the Pichichero et al study only included the smaller values.

 ?              The dose of ethylmercury given to subjects varied greatly and was less than what a typical child in the 1990s could be expected to have received. In the Pichichero study, the two-month-old subjects were injected with between 37.5 and 62.5 mcg of ethylmercury, giving a 67% variation between the lowest and the highest doses. A typical child in the 1990s might receive 62.5mcg of mercury at age two months, then an additional 12.5mcg at birth (from the HepB vaccine), in other words between 37% and 64% more than the children in the study. The six-month-olds in the study were injected with between 87.5mcg and 175mcg of ethylmercury, reflecting a 100% difference between the lowest/highest levels. By six months of age, a 1990s child would have received 187.5mcg, or 68% more than the Pichichero study group average.

 ?              In the Pichichero data, when the study characterizes blood samples drawn as being at “X” days after the mercury exposure, this is in fact misleading, because it refers only to the very last injection, and the reader actually cannot tell from the study data exactly how much dosage each infant received at the last exposure.

 ?              In this study, there was a single blood sample drawn from each child, and the collection times varied between 3 and 21 days for the two-month-old infants (giving a 700% variation) and from 4 to 27 days for the six-month-old infants (giving a 675% difference).

 

In concluding, Sally Bernard also makes a number of other profound criticisms of this study:

 ?              It makes improper use of methylmercury safety levels as a marker for ethylmercury risk

 ?              There has never been any full assessment of thiomersal safety. This has been admitted by the US Food & Drug Administration.

 ?     The Pichichero study does not address adverse outcomes (eg autism)

 

Her conclusion is that the Pichichero study does not offer the reassurance on thiomersal safety that is so widely claimed of it by the medical establishment. It is a small-scale descriptive study with many methodological limitations. It has little or no vale regarding thiomersal safety.

 

Pichichero also incidentally commented in January 2003 on the new 5-in-1 vaccine that was just then licensed by the US Food & Drug Administration. Welcoming the Pediarix-DTaP, hep B and inactivated poliovirus vaccine that was recommended for infants at 2, 4 and 6 months, Pichichero said that its advantage was that it offered “fewer injections for kids”, but, he then continued........”which would make room for new vaccines that are on the horizon”.

 

76.     Paper by Makela, Nuorti and Peltola, Neurologic Disorders after Measles-Mumps-Rubella Vaccination, Hospital for Children and Adolescents, Helsinki University Central Hospital, and Department of Infectious Disease Epidemiology, National Public Health Institute, Helsinki, Finland, published in Pediatrics, Vol 110 No. 5, November 2002, pp 957-963.

 

This was yet another retrospective study. The objective of the study was to assess whether an association prevails between MMR vaccination and encephalitis, aseptic meningitis and autism.

 

The study was based on the linkage of individual MMR vaccination data with a hospital discharge register. It was conducted amongst 535,544 one to seven year olds, who were vaccinated between November 1982 and June 1986 in Finland.

 

For encephalitis and aseptic meningitis, the numbers of events observed within a three-month risk interval after vaccination were compared with the expected numbers estimated on the basis of occurrence of encephalitis and aseptic meningitis during the subsequent three-month intervals.

 

Changes in the overall number of hospitalizations for autism after vaccination throughout the study period were searched for.

 

In addition, hospitalizations because of inflammatory bowel disease were checked for the children with autism.

 

The results were:

 

?              Of the 535,544 children who were vaccinated, 199 were hospitalized for encephalitis, 161 for aseptic meningitis and 352 for autistic disorders.

 ?              In 9 children with encephalitis and in 10 with meningitis, the disease developed within three months of vaccination, revealing no increased occurrence within this designated risk period

 ?     The study detected no clustering of hospitalizations for autism after vaccination

 ?     None of the autistic children made hospital visits for inflammatory bowel disease.

 

The following criticisms of this study were offered by Dr. Ed Yazbak of New Jersey:

 ?              The original Peltola study (from which this study has germinated) was completed by 1996, a full two years before the first autism/MMR paper was published by Wakefield et al in The Lancet, February 1998.

 ?              Peltola stated unequivocally in a BBC interview that his 1996-completed study did not address autism as a possible outcome from MMR vaccination

 ?              Subsequent authors have criticised the 1996-completed study as being irrelevant to proving an MMR/autism link, one way or the other. The Medical research Council review of 2001 admitted that the Finnish study by Peltola was not robust enough to be taken as conclusive evidence.

 ?              The Makela study does not account for why 352 cases of autism were hospitalised at all. Autism is not usually a condition that in itself leads to hospitalisation.

 

Conclusion: despite the supposedly large scale of this study, its fundamental methodological flaws mean that it cannot be deduced from its findings that there is no link between MMR and autism.

 

77.     Commentary by Nelson and Baumann, Thimerosal and Autism, Neuroepidemiology Branch of the National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, and the Children’s Neurology Service, Harvard Medical School, Boston, Massachusetts, published in Pediatrics, Vol 111, No. 3, March 2003, pp674-679

 

This paper looked at whether then-current evidence indicated that mercury at any known dose, form, duration, age or route of exposure leads to autism.

 

The paper commented:

 ?              There has clearly been a broadening of the criteria for autism (note: Yazbak reports that the reverse is the case), better case-finding, increased awareness by clinicians and by families, and an increase in referrals of children for services. Whether the sum of these is sufficient to account for the more frequent diagnosis of autism is a matter of contention....

?             Researchers Aschner and Walker (Molecular Psychiatry 2002, 7, S40-41) found no paper published in the peer-review literature that reported an abnormal body burden of mercury, or an excess of mercury in hair, urine or blood

 

?             Findings by other researchers support the observation that the risk of toxicity from ethylmercury is overestimated by comparison with the risk of intoxication from methylmercury

 

?             In both prenatally and postnatally exposed brain. the atrophy associated with neuronal loss and in the infant cases the reduced white matter volume suggest that these brains were likely to be reduced in size.....By contrast, examined at autopsy, brains of autistic persons are commonly enlarged both by weight and volume.....Thus, there seem to be major differences in the neuroanatomic findings in autism as compared with those in mercury toxicity.

 

?             If thimerosal was an important cause of autism, the incidence of autism might soon begin to decline (Note: it did, in 2004, in California).

 

?             Mercury poisoning and autism both affect the central nervous system, but the specific sites of involvement in brain and brain-cell types affected are different in the two disorders, as evidenced clinically and by neuropathology. Mercury also injures the peripheral nervous system and other organs that are not affected in autism. Overall, the clinical picture of mercurism from any known form, dose, duration or age of exposure does not mimic that of autism

 

?             On the basis of current evidence (the authors) consider it improbable that thimerosal and autism are linked

 

A commentary was provided by Sallie Bernard and Lyn Redwood of the US parents’ group Safe Minds:

 

?              Thousands of parents have reported biological and neurodevelopmental changes in their children directly following administration of mercury-containing vaccines. Symptoms, including sudden onset of shyness, GI distress, loss of motor skill functioning, allergies, the inability to speak, tremors and autonomic disturbances, mimic those associated with mercury poisoning

 

?              The Nelson/Bauman paper has a number of inaccuracies that call into question the paper’s conclusions. For example, they claim that survivors of acrodynia, a form of mercury poisoning, did not have behavioural disorders, suggestive of autism, but case descriptions clearly show that they did, such as loss of speech, odd behaviours and social withdrawal. Likewise, the authors remark that mercury studies from the Faroe Islands found no cases of autism, but these studies, by design, excluded any children with neurological disease.

 

?              The Pediatrics paper’s authors base their argument of thimerosal safety on a purportedly “weak association” between neurodevelopmental disorders and exposures to thimerosal-containing vaccines found by the CDC in an unpublished study (this refers to the Verstraeten study). The supposedly “weak association” is a mis-characterisation. Safe Minds obtained an earlier version of the CDC study (the suppressed version) that in fact found a 2.5 times increase in the risk of developing autism after exposure to increased thimerosal in vaccines. In a court of law, a relative risk of 2.0 or greater is sufficient to substantiate that a given exposure caused disease.

 

These serious criticisms suggest that the Nelson & Bauman study remains ambiguous in its implications, and cannot be taken as evidence that thimerosal in vaccines is safe.

 

78.     Study by Madsen, Lauritsen, Pedesen et al, Thimerosal and the Occurrence of Autism: Negative Ecological Evidence from Danish Population-Based Data, Pediatrics, 2003 Sept 112(3) 604-606

 

This study is not to be confused with the Madsen et al study into MMR, referred to earlier and which was published shortly afterwards in the New England Journal of Medicine.

 

The study examined whether discontinuing the use of thimerosal-containing vaccines in Denmark led to a decrease in the incidence of autism. The study analysed data from the Danish Psychiatric Central Research Register, recording all psychiatric admissions since 1971 and all outpatient contacts in psychiatric departments in Denmark since 1995.

 

The patients included all children between 2 and 10 years old who were diagnosed with autism during the period from 1971-2000.

 

A total of 956 children, with a male to female ratio of 3.5 to 1, had been diagnosed with autism during the period 1971-2000. There was no reported trend towards an increase in the incidence of autism during that period when thimerosal was used in Denmark, up through 1990. From 1991 until 2000, the incidence increased and continued to rise after the removal of thimerosal from vaccines, including increases amongst children born after the discontinuation of thimerosal (in Denmark).

 

The study authors concluded that the discontinuation of thimerosal in 1992 was followed by an increase in the incidence of autism, and that the data did not support a correlation between thimerosal-containing vaccines and the incidence of autism.

 

There are some very serious criticisms of this study. Firstly, if autism was linked to thimerosal (which was reduced) and the intensity of the vaccination schedule (which was increased) during the study period, the two factors could work against each other, masking trends and confounding the study conclusions.

 

Also, if the take-up of MMR and any consequential effect on autism increased, or the increased effect of another factor, such as antibiotic use, came into play, this too would confuse the study outcomes.

 

The study also fails to differentiate between different types of autism. The focus of investigation on autism is upon late-onset/degenerative autism. As this study does not address this, it offers no insight into the MMR/thimerosal/autism controversies.

 

The study did not declare an obvious conflict of interest, that two of the authors were working for the Danish manufacturer of thimerosal vaccines. The journal Pediatrics also receives substantial advertising revenues from vaccine manufacturers. The American Academy of Pediatrics was in part responsible for recommending new thimerosal-containing vaccines into the US.

 

The study was criticised by Dr. Robert Byrd of the MIND Institute, University of California at David, who pointed out that it only used data on hospitalised autistic children up until 1995, then added-in outpatients after that date. This would have confused any assessment of changes in autism rates.

 

The parents’ group Safe Minds alleged that the increase purported to have been demonstrated during the 1990s was not real, and was “falsely created by the authors using three deceptive techniques”:

 

?              Firstly, the authors added outpatient autism cases to their database from 1995 onwards, as noted. These outpatient cases outnumbered existing inpatient cases by 13.5 to 1, and represented 93% of all autism cases, thus artificially boosting case numbers from 1995. No account of this is taken by the authors.

 

?              Secondly, the authors added cases from a large clinic in Copenhagen, starting in 1992. Previously, records from this centre were excluded. The centre accounted for 20% of the caseload in Denmark. No allowance was made by the authors for this factor.

 

?              Thirdly, in 1994 the Danish psychiatric system changed its classification scheme and began to diagnose autistic patients under the infantile autism criteria (ICD-10) rather than the old psychosis proto-infantilis (ICD-8), a category that has never been used in published autism surveys outside Denmark. The old category would have excluded a proportion of autistic children, relative to the new criteria.

 

Mark Blaxill of the US group Safe Minds also commented: “The autism trend data are described as an “incidence study”. But the report is in  no way a proper incidence study. It relies instead for its definition of the “incidence” of autism on the date when cases were entered into the new registry of outpatients. Many of these children were between 7-9 years old, and most were over 4 years old, when recorded as part of an increasing “incidence” trend. Yet the onset of autism must occur, by definition in the diagnostic criteria, before three years of age. Recording incidence at, say, seven years is clearly incorrect.”

 

Blaxill also comments: The report also estimates inpatient rates for the pre-1993 psychosis proto-infantilis at well below 1 per 10,000. If these were true rates for autism, these would be amongst the lowest rates measured anywhere in the world at any time period. This low rate would also contradict the single published survey of autism rates from Denmark, which indicated an autism rate of over 4 per 10,000 as far back as the 1950s. Madsen et al fail to mention this study, as they fail to comment on the unusually low autism rates for the earlier years of their study period.”

 

Blaxill concludes that there in fact only three conclusions that can be drawn from the Madsen study:

 

?              The rates in the 1990s are low compared with the US and UK and possibly stable with respect to trend

 

?              The 1990s Danish autism rates are similar to rates in the 1950s

 

?              There are still no published usable data about Danish autism rates in persons born 1960-1990.

 

Blaxill concluded: “In summary, the report by Madsen et al appears to be an attempt to present selectively-chosen data that provide support for policy choices in which the authors and their collaborators are involved.”

 

The study was also strongly criticised in a well-argued paper by Dr. F. Edward Yazbak, Studies That Count, Studies That Don’t:

 

?             The present rise in autism in Denmark has clearly started 4 or 5 years after the introduction of the MMR vaccine, and it appears to correspond with the percentage of children who received MMR

 

?             The mean age at the time of diagnosis in Denmark is probably around 4.7 years. Approximately 25% of autism cases in Denmark are reported in children under the age of 5 with the remaining 75% of affected children being reported when they are 5 to 19 years old

 

?              Given these percentages, any inferences about disease in the under-5 group, in which the disease has not yet become manifest, are potentially flawed

 

?              The 2,129,864 person-years reported in the Madsen study divided by the number of children (537,303) indicates that the average age of the children in the study is less than 4 years (range 1 to 7 years). Those children would be 5 to 12 years old in 2003. Because the mean age at diagnosis is 4.7 years in Denmark, the Madsen study could not have detected many of the cases of autism that were subsequently diagnosed when these children were older, thereby missing the temporal connection between MMR and autism

 

?             The 0 to 4 year old group of children (in the Madsen study data) remains the lowest from 1980 to 1991, because autism was/is rarely diagnosed under the age of 4 in Denmark. The prevalence of autism in that age group starts climbing after 1991, 4 years after the introduction of the MMR vaccine, to become the second-highest by 1993.

 

?              The 5-9 age group is the earliest cohort that received the MMR vaccine after coverage had improved, and is also old enough to be diagnosed. There are consistently more and more affected children in this age grouping.

 

?              The 10 to 14 age group (in the data) represents the earlier cohort that first received MMR but at lower coverage rates. Those affected children aged 10-14 in 2003 were aged 1 to 5 in 1994. They reflect the start-up of the autism increase associated with the start-up and progression of the MMR vaccination programme.

 

?              The 15-19 age group were aged 1 to 5 in 1989; their number (in terms of autism) increases but at a much slower rate than in the younger age groups.

 

?              Lastly, argues Yazbak, the 20 to 24 age group shows only a slight increase, starting in 1994, possibly because few if any of this cohort received MMR at a vulnerable age.

 

?              Even when one takes into account the classification change that took place in 1993-94 and the addition of outpatients to the database in 1995, it is evident, when five additional years are considered, that the conclusions of the Madsen study are invalidated and that the data appears to support the hypothesis that increases in autism in Denmark may be correlated with increases in percentage coverage and number of children receiving MMR.

 

?              It is likely that the 0-4 year group of affected children represents those who were not generally diagnosed earlier, and that the 5-9 age group represents the highest increase that occurred after widespread coverage of MMR, and that the 10-14 age group represents the earlier cohort that first received MMR but at a lower coverage rate (for further details, see the Madsen study, and the Yazbak paper)

 

?              Yazbak then argues that the rate of autism would now level-off at the higher rate, since children receiving MMR immunisation have now saturated the age-groups and replaced individuals in the age -groups that were previously unvaccinated

 

?              When MMR vaccination coverage improved beyond a certain level, from 1993-2001, there was a steady and increasing trend in autism every year. That gradual rise levelled-out after the entire cohort aged less than 10 years was almost completely vaccinated. It is therefore entirely possible that many of the children in the most-affected 5 to 9 group could have started with symptoms as early as the second year of life

 

?              The prevalence rate of autism in Danish children under the age of 14 has increased by 729% from 17.67 per 100,000 population (1 in 5,659) in 1980 to 146.42 in 100,000 (1 in 683) in year 2002.

 

?              The prevalence of autism in children and teenagers under the age of 14 in Denmark, which was 131.42 per 100,000 (1 in 761) in the seven years before MMR vaccine, increased by 542% to 843.73 per 100,000 (1 in 119) in the most recent seven years.

 

?              Two doses of MMR are administered in Denmark, one at age 15 months and one at age 12 years. The Madsen data suggests that the main concern is the vaccination given at age 15 months.

 

?              The prevalence of autism in Denmark in the 0 to 14 year-olds levelled-off in the latest three years, when toddler MMR coverage reached the 95%-98% level. The reason why this did not similarly take place in the US in the 1990s was probably because pediatric vaccines in the US contained thimerosal, further underpinning the argument that the Madsen study was fundamentally flawed in principle because countries with strikingly-differing vaccination practices cannot and should not be compared.

 

Dr. Yazbak concludes that autism has increased in Denmark after the introduction of the MMR vaccine, as evidenced by the fact that the rate ratio (ie the incidence of autism after versus before MMR introduction) is 8.8, among 5-9 year old Danish children. The Madsen study did not reveal this statistically-significant increase.

 

79.     Hviid, Stellfeld et al , Association Between Thimerosal-Containing Vaccine and Autism, Journal of the American Medical Association, Oct 1st 2003 vol 290, no.3, pp1763-66.

 

The objective of this study was to determine whether vaccination with a thimerosal-containing vaccine is associated with development of autism.

 

The study was a population-based cohort study of all children born in Denmark from Jan 1st 1990 until Dec 31st 1996 (467,450), comparing children vaccinated with a thimerosal-containing vaccine with children vaccinated with a thimerosal-free formulation of the same vaccine.

 

The study results were:

 

?              During 2,986,654 person-years, the study identified 440 autism cases and 787 cases of other ASD

 

?              The risk of autism and other autistic-spectrum disorders did not differ significantly between children vaccinated with thimerosal-containing vaccine and children vaccinated with thimerosal-free vaccine

 

?              There was a relative risk 0.85 for autism

 

?              There was a relative risk of 1.12 for other ASD

 

?              The study found no evidence of a dose-responsive association for autism and other ASD

 

The study concluded that its results did not support a causal relationship between childhood thimerosal-containing vaccines and the development of autistic-spectrum disorders.

 

This study was heavily criticised. Rep. David Weldon, US Congress, commented:

 

?             Hviid works for the Danish Epidemiology Science Center, which is housed in the Staten Serum Institute, the government-owned Danish vaccine manufacturer

 

?              All of his co-authors work with him at the Center or are employed by the SSI

 

?              Staten Serum makes a considerable profit from the sale of vaccines and vaccine components

 

?              If Hviid were to find an association between thimerosal and autism, the SSI.....would face significant lawsuits

 

?              Danish children received 75mcg of mercury by 9 weeks and another 50mcg at 10 months. By comparison, children in the US received 187.5mcg of mercury by age 6 months  -  nearly two and a half times as much mercury as Danish children in just the first 6 months of life......Comparing the exposures in the US to those in other countries is like comparing apples and cows

 

?              Hviid states that the rate of autism went up after they began removing thimerosal from vaccines in 1992. The numbers in the Hviid study are skewed in that they added outpatient autism diagnosis to the number after 1992.....Like the Verstraeten study, Hviid would not be able to pick up a group of children who were genetically susceptible to mercury toxicity.

 

?              Danish autism rate is about 6 in 10,000 (1 in 1,666), vs 30 in 10,000 (1 in 333) in the US.....Indeed, I believe it can legitimately be argued that the lower rate of autism in Denmark is attributable to the lower exposure to mercury in their population

 

80.     Study by Miller, Taylor et al, Bacterial Infections, Immune Overload and MMR Vaccine, published in Archives of Diseases in Childhood, 2003; 88; 222-223

 

This was a further paper by Dr. Elizabeth Miller and Professor Brent Taylor and co-researchers. The hypothesis tested was that, if MMR does induce clinically significant immunosuppression, susceptibility to infection should be increased during the post-vaccination period.

 

?              The authors tested this hypothesis using cases of invasive bacterial infection and pneumonia in children aged 12-23 months admitted to hospital between 4/91 and 3/95.

 

?              The study conclusion was that MMR vaccine did not increase the risk of hospitalisation.

 

The study was part-funded by GlaxoSmithKline, the manufacturers of MMR.

 

Congressman Rep. David Weldon commented:

 

?              The Miller study examines the population of children in the UK. This study is still unpublished (Note: in terms of raw data), which limits a critical and public evaluation of its findings

 

?              Dr. Miller has actively campaigned against those who have raised questions about vaccine safety. She and her Department (the UK Public Health Laboratory Service, now part of the Medicines and Healthcare Regulatory Agency) receive funding from (the) vaccine manufacturers who are being sued

 

?              This study, like the Verstraeten study, is a dose response study, which is limited in that it does not compare children who receive thimerosal to those who did not

 

Comment: this study did not examine how children who became autistic were healthy before MMR and degenerated into autism in the period (often longer than three months) following vaccination. It did not clinically examine children. It offers no convincing evidence against the alleged link between MMR and autism. It is puzzling, if child health datasets are so readily available, as to why these researchers did not compare rates of autism between large cohorts of children who (a) had received MMR, (b) had received single vaccines and (c) were unvaccinated altogether (with measles-containing vaccine, although a fourth cohort could include children who had not had either DTP or MMR. Surely, studies of such groups could readily expose different rates of autism, were they to exist, provided the groups were large enough?

 

81.     Further study by Taylor, Miller et al, Archive of Diseases In Childhood, 2003, 88, 666-670

 

This study looked at a cohort of 567 children in five districts in NE London who were born between 1979 and 1998 and who had been given a diagnosis of ASD.

 

?              The study showed that the condition reached a plateau between 1992 and 1996, of 2.6 cases per 1000 live births (1 in 385). This followed an apparent rise from 1979 until 1992

 

?              the study argued that if autism was associated with MMR, the number of cases should have increased throughout the early 1990s, as MMR was introduced in the UK in 1988. Taylor argued that the rise occurred before MMR

 

?              the latest figures in the study showed “only” 45 to 50 cases (this in these districts, not across the UK) being diagnosed each year between 1992 and 1996

 

?              the study noted that MMR was cited as the trigger in two out of 46 cases before August 1997, but this proportion increased to six out of 30 cases (20%) after 1997, due to the publicity surrounding the February 1998 Wakefield paper

 

The researchers commented that the apparent plateau in cases, plus the drop in age at diagnosis, “suggests that the earlier recorded rise in prevalence was not a real increase but was likely to be due to factors such as increased recognition, a greater willingness on the part of educationalists and families to accept the diagnostic label, and better recording systems”.

 

Professor Taylor was quoted as stating: “The claims that MMR vaccine is involved in the initiation of autism, and/or with regression, and/or with bowel problems associated with autism, are not associated with any credible scientific evidence, while there is compelling and increasing evidence showing no association.”

 

Comment: as usual, this study took a simplistic line of inquiry, treating data on increases in autism as though it should behave in a direct linear relationship with MMR’s coverage, finding that it did not, and concluding that the two could not possibly be connected.

 

The study was based upon data that was less than trustworthy in nature. Autism diagnosis is not always given to children with autism, in any formal way, and even if given, is often delayed.

 

The study treats all autism as being the same, failing to differentiate those cases where a child developed normally and then regressed inexplicably  -  the focus of the MMR/autism debate. This was a crucial failure. No-one is suggesting that all autism is caused by MMR, and it is vital to distinguish between children who were progressing satisfactorily pre-MMR and those who were not.

 

No children were clinically examined in this study.

 

The study is also far too willing to “explain” its findings (“Likely due to factors such as increased recognition”) without providing scientific evidence to support these conclusions. The finding that increases were due to better recognition does not accord with the much more detailed study by Byrd et al in California, which reported in late 2002 (before this London study was published), which found that increases were real.

 

The study also does not allow for the possibility of two potential causes being at work, increased take-up of MMR and increased intake of thimerosal. This, of course, would invalidate the study findings.

 

Overall comment: this study fails to provide any convincing contribution to the MMR/autism and thimerosal/autism debate.

 

82.     Article by Verstraeten, Davis, DeStefano et al, Safety of Thimerosal-Containing Vaccines  -  A Two-Phased Study Of Computerized Health Maintenance Organisation Databases, published in Pediatrics, vol 112, no. 5, November 2003

 

(note: Verstraeten, the lead author, was accredited in this paper as being part of “the Vaccine Safety Datalink Team at the time of the study”. In fact, at the point of publication, he had been working for several years for GlaxoSmithKline  -  manufacturers of thimerosal-containing vaccines, who were potentially-facing a large number of legal cases)

 

The study objective was to assess the possible toxicity of thimerosal-containing vaccines (TCVs) among infants

 

?              A two-phased retrospective cohort study was conducted, using computerised health maintenance organisation (HMO) databases 

?              Phase one screened for association between neurodevelopmental disorders and thimerosal exposure amongst 124,170 infants who were born during 1992 to 1999 at two HMOs (“A” and “B”) 

?              Phase two was that the most common disorders associated with exposure in phase one were re-evaluated among 16,717 children who were born during 1991-97 in another HMO (HMO “C”) 

?              Relative risks for neurodevelopmental disorders were calculated per increase of 12.5ug of estimated cumulative mercury exposure from TCVs in the first, third and seventh months of life

 

?              In phase one at HMO A, cumulative exposure at three months resulted in a significant positive association with tics (relative risk 1.89). At HMO B, increased risks of language delay were found for cumulative exposure at 3 months rr 1.13) and 7 months (rr 1.07)

 

?              In phase two, at HMO C, no significant associations were found.

 

?              In no analyses were significant increased risks found for autism or attention-deficit disorder (but see later section in this Briefing Note, covering evidence for an association, for further details on these claims and on this study’s re-working of its statistics)

 

The study conclusions were:

 

?              No consistent significant associations were found between TCVs and neurodevelopmental outcomes

 

?              Conflicting results were found at different HMOs for certain outcomes

 

?              For resolving the conflicting findings, studies with uniform neurodevelopmental assessments of children with a range of cumulative thimerosal exposures are needed

 

Congressman David Weldon MD offered the following comment on this study:

 

“Most recently, the CDC produced an article by Dr. Verstraeten, published on November 3rd.....Dr. Verstraeten is a former CDC employee. Since 2001 he has worked for GlaxoSmithKline, a vaccine manufacturer. While working for the CDC in 2000, the first version of Dr. Verstraeten’s unpublished study found an association between higher thimerosal exposures and neurodevelopmental disorders, including autism. Between 2000 and 2003, Dr. Verstraeten and co-authors manipulated and stratified the data so much that each of these associations magically disappeared. I don’t know if it was deliberate, but that is nonetheless what happened. This (latest published) study has done nothing in my mind to put those concerns to rest, but only serves to raise suspicions.”

 

“In a recent article (Expert Review of Vaccines), Dr. Verstraeten et al state that ‘Any pharmacoepidemiologist working on a (large linked database) will soon be tempted to construct models with multiple strata and covariants in an effort to adjust for every possible confounder available. The large number of variables and multiple strata make it virtually impossible to understand how the results from the crude data differ from the final analyses, which have therefore been referred to as ‘Black Box Analyses’.” This over-stratification appears to be the exact method employed in the final version of the published Pediatrics study.”

 

This study was also heavily criticised by Geier and Geier. They pointed out:

 

?              The head author, Verstraeten, had worked for the previous several years for GlaxoSmithKline, a company that had manufactured millions of thimerosal-containing vaccines and which faced many lawsuits over thimerosal’s links with autism

 

?              This was the same basic study that had been the subject of the 2000 Simpsonwood meeting, where it had been revealed that the initial study had found statistically-significant dose-response effects between increasing doses of mercury from thimerosal-containing vaccines and various neurodevelopmental disorders

 

?              that meeting had expressed the desire for the data to be “handled”. Even Verstraeten himself had expressed surprise in a subsequent email that the data was to be manipulated, stating that one’s desire to disprove an unpleasant theory should not interfere with sound scientific methods to evaluate the relationship between thimerosal and neurodevelopmental disorders

 

?              There were also significant issues about the methods used to determine the mercury dose that children received from vaccines. Calculations indicate that Verstraeten et al did not take thimerosal-free DTaP vaccine into account in their study, or if they did, then their paper as it stands is replete with inaccurate information

 

83.     Paper by Stehr-Green, Tull, Stellfeld et al, Autism and Thimerosal-Containing Vaccines; Lack of Consistent Evidence for an Association, published in the American Journal of Preventative Medicine, 25 (2003), pp101-106

 

The study’s methods were:

 

?     Between the mid-1980s and through the late 1990s, the team compared the prevalence/incidence of autism in California, Sweden and Denmark with average exposures to thimerosal-containing vaccines

 

?     Graphic ecologic analyses were used to examine population-based data from:

 

?the United states (national immunisation coverage surveys and counts of children diagnosed with autism-like disorders seeking special educational services in California

 

?Sweden (national inpatient data on autism cases, national vaccination coverage levels, and information on use of all vaccines and vaccine-specific amounts of thimerosal

 

?Denmark (national registry of inpatient/outpatient-diagnosed autism cases, national vaccination coverage levels, and information on use of all vaccines and vaccine-specific amounts of thimerosal

 

The results were:

 

?               In all three countries, the incidence and prevalence of autism-like conditions began to rise in the 1985-89 period, and the rate of increase accelerated in the early 1990s

 

?              However, in contrast to the situation in the US, where the average thimerosal dose from vaccines increased throughout the 1990s, thimerosal exposures from vaccines in both Sweden and Denmark  -  already low throughout the 1970s and 1980s  -  began to decrease in the late 1980s and were eliminated in the early 1990s

 

The conclusions were that the body of existing data, including the ecologic data presented therein, is not consistent with the hypothesis that increased exposure to thimerosal-containing vaccines is responsible for the apparent increase in the rates of autism in young children being observed worldwide.

 

The study was once again very strongly criticised. Mark Blaxill of Safe Minds commented:

 

  *     the authors minimized the severity of the California situation, where high and rising autism rates pointed to a public health emergency, and merited accurate measurement and precise classification

 

  *     The study’s autism cases accounted for only a fraction of the real autism population. The large majority of autism cases were to be found in outpatient populations. Yet the study’s analyses in Sweden (exclusively) and Denmark (for two-thirds of the study period) relied on inpatient population data.

 

  *     one recent Danish study (Madsen) revealed that 93% of autistic records were for outpatients. Clearly, the small remaining group of inpatient registrations would have little value in trend assessment

 

  *     the rate and exposure assessments in the study contained multiple errors. Despite these flaws, the study team claimed that the choice of Swedish and Danish sources was based on ‘high quality records’.

 

  *     the study authors’ interpretation of the autism-mercury hypothesis is incorrect. Based on flawed trend assumptions, the authors use the shift in Sweden and Denmark to thimerosal-free vaccines in an attempt to falsely-interpret the autism-mercury hypothesis

 

  *     reductions in comparatively-low thimerosal exposures need not produce decreasing autism rates in stable low-prevalence populations for the autism-mercury hypothesis to hold

 

  *     the authors’ attempts at trend analysis demonstrate the dangers of misinterpreting ecologic analyses, especially when relying on shifting data sources and incomplete time-series

 

84.     Paper, Age At First MMR Vaccination In Children With Autism and School-Matched Control Subjects: A Population-Based Study In Metropolitan Atlanta, DeStefano, Bhasin, Thompson, Yeargin-Allsopp and Boyle, Pediatrics, 2004; 113: 259-266

 

(note: several of the participants, including DeStefano, Yeargin-Allsopp and Boyle, have a high-profile involvement in the MMR controversy, and their work can be found elsewhere in this Briefing Note. DeStefano has co-authored papers with the UK’s Dr. Elizabeth Miller, and also was a critical peer-reviewer of the Wakefield team’s 1998 Lancet paper)

 

The objective of this paper, curiously, was to compare ages at first MMR vaccination between children with autism and children who did not have autism, in the total population and in selected subgroups, including children with regression in development.

 

A case-control study was conducted in metropolitan Atlanta, comparing 624 autistic cases with 1,824 controls. Vaccination data was abstracted from immunisation forms required (in the US) for school entry. Records of children born in Georgia were linked to birth certificates for information on maternal and birth factors.

 

The results were:

 

?              The overall distribution of ages at MMR vaccination among children with autism was similar to that of matched control children

 

?              Most case (70.5%) and control (67.5%) children were vaccinated between 12 and 17 months. Similar proportions of cases and controls had been vaccinated before 18 months or before 24 months.

 

?              No significant associations for either of these age cut-offs were found for specific subgroups, including those with evidence of developmental regression

 

Comment  -  this study, which compares age of exposure to first MMR between cases of autism and controls without autism, has been very heavily criticised on numerous fundamental aspects:

 

?              The hypothesis is a very strange one to test. It has never (as far as is known) been previously proposed. It is not appropriate to draw such a hypothesis from the 1998 Lancet paper by Wakefield et al, as the authors seem to do.

 

?              Ironically, the study does show a positive association between age at first MMR and a risk of autism. DeStefano and colleagues’ data actually confirms a striking positive trend towards (a) exposure to MMR before 36 months, and (b) autism. This is particularly so with the younger cohorts.

 

?              The attempt to ascertain regression status from a retrospective analysis of patient records is wholly flawed and pointless. This is because (a) the process of regression, or alternatively the absence of regression as a feature of the child’s condition, does not normally form part of the diagnostic process of autism. Secondly, (b) the very concept of regression is not recognised by many paediatricians, because the common view is that the child was “always” autistic but that the parents failed to notice it. The very detailed review of cases carried out by UK lawyers confirmed these facts. Patient record data is therefore meaningless for this study’s purpose.

 

?              Detailed data provided by Dr. Bernard Rimland of the US Autism Research Institute has exposed how unrepresentative DeStefano and colleagues’ data is in the context of regression status.

 

?              Without providing any justification, DeStefano et al seek to explain-away the MMR/autism observation by saying that it is likely to reflect the vaccine entry requirements for special education. If that was truly the case, then the MMR/autism link should also have been seen in the other autistic groups who had earlier mental retardation (as well as in those who did not, and only later regressed)  -  but it is not.

 

?              The study is also mis-designed, because it underestimates numbers of children who will ultimately receive a diagnosis of autism. This is because the mean age of diagnosis is five years, but the study control group includes many children under five.

 

?              Worse still, the children that are most likely to be underrepresented  -  non-autistic controls, who then later receive an autism diagnosis  -  are the late-onset regressive children with an earlier normal IQ, in other words, the very children we are most concerned about

 

To summarize, the “explanations” offered by the DeStefano study are invalid. The DeStefano et al study should therefore be a cause for actual deep official concern, not reassurance.

 

In addition to these epidemiological criticisms, this study of course was just that  -  an epidemiological study, of records that would reveal little of relevance. No children were clinically examined.

 

Conclusion: this study offers no evidence of MMR’s safety, and cannot in any way be taken as a proven contradiction of other clinical studies that point to an MMR/measles virus/gut/autism link.

 

85.     Paper, A Voxel-Based Investigation of Brain Structure In Male Adolescents With Autistic Spectrum Disorder, Waiter, Williams et al, University of Aberdeen, Royal Cornhill Hospital Aberdeen and University of St. Andrews, Scotland, published in Neuroimage, Vol 22, Issue 2, June 2004, pp619-625

 

This study reported a voxel-based morphometric whole brain analysis using a group-specific template on 16 individuals of normal intelligence with ASD and a group of 16 age- sex and IQ-matched controls.

 

?              Total grey matter volume was increased in the ASD group relative to the control group, with local volume increases in the right fusiform gyrus, the right temporo-occipital region and the left frontal pole extending to the medial frontal cortex

 

?              A local decrease in grey matter volume was found in the right thalamus. The increase in grey matter volume in ASD subjects was greatest in those areas recognised for their role in social cognition, particularly face recognition (right fusiform gyrus), mental state attribution, “theory of mind” (anterior cingulate and superior temporal sulcus) and perception of eye gaze (superior temporal gyrus).

 

The study authors concluded that the picture may reflect an abnormally functioning social cognitive neural network, and that it suggested that increased grey matter volume may play a pivotal role in the aetiology of ASD.

 

The press commentary that accompanied this article was high in its claims. Dr. Justin Williams (co-author) claimed that the findings demonstrated unequivocally that the MMR vaccine could not be responsible for causing autism: “This study indicates that autism is the result of normal development processes not taking place......The bottom line is that autism is not the product of brain damage”.

 

Dr. Robert Minns (not a co-author) stated that the study “.....proved beyond doubt that autism could not be linked with MMR”.

 

However, the autism expert Dr. Ken Aitken commented: “This appears to be a further study showing that there are differences in grey-white matter distribution in autism. It does not seem to add anything further to the various recent studies.”

 

“The conclusion drawn should clearly be that there are likely to be various different.....possible causes of autism.”

 

Another researcher commented: “Excess grey matter in children with autism would be entirely consistent with the effects of exogenous opioid peptides which interfere with the normal process of programmed neuronal death (apoptosis). These findings support such a mechanism, and provide indirect evidence for gastrointestinal-related disease induced by MMR.”

 

Conclusion: this study does not disprove an MMR/autism link in cases of regressive autism. The study incidentally does not differentiate between regressive autism and other forms of ASD  -  a crucial failure.

 

PART H

 

REVIEWS CONCLUDING THERE IS NO EVIDENCE OF A VACCINE/AUTISM LINK

 

(again, it is important to point out that all these reviews were only desk studies. No actual damaged children were examined)

 

86.     Medical Research Council Review By “Committee of 37 Independent Experts”

 

This was held as a one-off in March 1998 to examine the Wakefield team’s “Early Report” published in 2/98 in The Lancet. It concluded

 

?         that there was no current evidence linking bowel disease or autism with MMR

 

?         there was thus no reason, arising from the work considered, for a change in the current MMR vaccination policy” (my emphasis - note the careful wording)

 

This review has now been overtaken by subsequent events, yet it continues to be quoted by the UK Department of Health, as though time had stood still.

 

87.      Paper, Conclusions on MMR Vaccine Safety by the All Party Parliamentary Group on Primary Care and Public Health, House of Commons, UK (based on a presentation by Dr. Elizabeth Miller, Head of the Immunisation Division, Public Health Laboratory Service)

 

This paper reported on its review of MMR’s safety, based upon a presentation by Dr. Elizabeth Miller of the Public Health Laboratory Service on 24th July 2000.

 

There are a number of serious concerns about this paper:

 

?         The conclusion of the APPG and its invitees was that MMR was safe, and that concerns about the alleged links with autism/inflammatory bowel disease were unfounded. However, this is a very strong claim, in the absence of appropriate comprehensive studies. If a link is “unproven”, that does not necessarily mean that a concern is therefore categorically “unfounded”.

 

?         Dr. Miller had demonstrated that MMR has enabled “excellent” control of measles, but that is not the point at issue.

 

?         There was concern at the fall in MMR take-up. This, too, is not what is under scrutiny. It is MMR’s safety that is in question. Concern over measles outbreaks and falling take-up may be legitimate, but are arguably being used here as a form of moral pressure.

 

?         The APPG expressed concern about measles outbreaks elsewhere, e.g. Holland. The same comment applies. It is MMR’s safety in the UK that is under scrutiny.

 

?         The statement that “all (hypotheses about a link) have originated from a single group of workers in the UK” (at the Royal Free), and “none has been endorsed by independent recognised medical experts anywhere in the world” is highly misleading. The Royal Free team have been at the forefront of research, but their work has been given backing by other researchers (to give just one example, the letter in the Lancet by Sabra, Bellanti and Colon, 1998), and the possibility of a link has been endorsed, or has been unable to have been ruled out, by other researchers. Other studies and reviews have been inconclusive either way. The position is still one of scientific uncertainty.

 

?         Claims that the Joint Committee on Vaccination and Immunisation “is composed of independent clinical and scientific experts” are open to question. The JCVI does not include gastroenterologists  -  which is the key area of science under scrutiny in this issue. Its independence can also be questioned on two counts. Firstly, a number of its members have declared financial links with the pharmaceuticals industry. This could be argued to part-compromise their independence. Secondly, there is a collective professional interest in eliminating infectious diseases through immunisation. Such a body is therefore not wholly “independent” when it comes to assessing evidence for adverse side effects from vaccines, particularly if it involves a syndrome which, if acknowledged, could damage confidence in vaccines and lead to a resurgence in communicable diseases.

 

?         The Committee on Safety of Medicines is also questionably “independent”. It is a matter of record that 37 members of the CSM had between them, at the end of the 1990s, nearly 190 separate declared financial links with the pharmaceuticals industry, about one-half of which were personal financial links. Some of these links involve the manufacturers of MMR. The 190 links include shareholdings, consultancies, research funding and non-executive directorships. An impartial observer would find that these links could arguably weaken any claims of “independence”.

 

?         The claim that “there is no evidence” (for a link) is factually incorrect (see elsewhere).

 

?         Claims of “overwhelming evidence” (against any link) do not address the inconclusive nature of many of the studies involved. There is still no hard evidence against a link. These studies also conflict with the direct first-hand accounts of the parents of the children believed to have been damaged.

 

It is disturbing, if understandable, that the All Party Group should produce such a report. The Group appears to have been given a  presentation of only one side of the argument.

 

This review, too, has long since been overtaken by subsequent events.

 

88.    The Medical Research Council’s Report, Report of the Strategy Development Group Sub-Group on Research into Inflammatory Bowel Disorders and Autism, March 2000

 

This was yet another review group which, upon failing to prove that there was a link, then drew the unproven conclusion that, because they could not find one, it automatically followed that there was no link.

 

Membership of the group was messrs. McGregor (chairman), Driscoll, Frith, Jewell, Meade, Sewell, Smith, Tedder, Ward, Wing, Wright. The sub-group met four times, 1998-99.

 

?         The group was to develop a strategy for further research, monitor and steer future MRC support, and report at least annually.

 

?         The subgroup recognised that the level of MRC support, particularly for IBD (but why not autism?) was “relatively weak”.

 

?         The subgroup found that the case for autistic enterocolitis was unproven, and that the California autism increase “may be due to wider definitions and increasing awareness”, though it offered no scientific evidence to support this self-comforting claim.

 

?         It concluded that much remained unknown about autism and IBD, that MRC support for research was weak, and that “between March 1998 and September 1999 there had been no new evidence to suggest a causal link” (again, note the careful wording).

 

For autism, its recommendations included:

 

?         Investigation of risk factors, large-scale epidemiological studies concentrating on late-onset cases (this led directly to the Professor Andrew Hall three-year study at London School of Hygiene & Tropical Medicine, but seemingly, to little else)

 

?         Development of tests to investigate gastrointestinal involvement in autism (no progress on this has since been reported)

 

?         Maintaining a watching brief for further evidence of any link

 

Despite the above, which implied continued vigilance, the chairman was openly dismissive of even the possibility of a link emerging, Professor Alan McGregor telling Reuters “We see this as the end of the story” (Reuters, 3/4/00).

 

89.     Review By US Institute of Medicine, 2001

 

The Institute of Medicine undertook a review of the link between MMR and autism during 2001.

 

The Immunisation Safety Review Committee was asked to assess not only the scientific plausibility of the hypothesised association between MMR and autism but also the significance of the issue in a broader context. In the IoM’s view, the plausibility assessment involved two components:

 

?         An examination of the causal relationship between the vaccine and the adverse event

 

?         An examination of any pathogenic mechanisms that support the hypothesis

 

The IoM set out a number of important reservations regarding the heavy reliance on epidemiological studies to prove/disprove any MMR/autism link:

 

?         Studies may not have sufficient precision to detect very rare occurrences at a population level

 

?         A poor understanding of the risk factors and a failure to use a standard case definition may also hamper the ability of epidemiological studies to detect rare adverse events

 

?         Since MMR is virtually universal in developed countries, elucidating any association with adverse outcomes requires the creative use of administrative and other data sets and complex research designs

 

?         The rarity of the individual autistic spectrum disorders, and the difficulty in determining their exact onset, and therefore the temporal relationship between onset and vaccination, makes certain epidemiological study designs (e.g. cohort studies) impractical.

 

The IoM Committee concluded that the evidence favours rejection of a causal relationship. However, the Committee also noted:

 

?         Its conclusion did not exclude the possibility that MMR vaccine could contribute to autism in a small number of children

 

?         The epidemiological evidence lacks the precision to assess rare occurrences of a response to MMR leading to autism

 

?         The proposed biological models linking MMR vaccine to autism, although far from established, are nevertheless not disproved

 

In a critique of the IoM Review in Autism Research Review International Newsletter, Vol. 15, No. 2, 2001, Dr. Bernard Rimland of the Autism Research Institute stated:

 

?         The IoM did in fact not reject the hypothesis that MMR is a possible cause of autism (the IoM review is regularly quoted by the UK Depa