http://pediatrics.aappublications.org/cgi/eletters/112/5/1039#782

False information in DeStefano/Rhodes response to M. Geier 24 March 2004
(see http://pediatrics.aappublications.org/cgi/eletters/112/5/1039#747 )
    
Brian S. Hooker,
Research Scientist
Autism Healing Network
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Re: False information in DeStefano/Rhodes response to M. Geier


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 Dear Editor

The coauthors of the Verstraeten et al. 2003 Pediatrics study erroneously
report in their P3R response to Dr. Mark Geier, that the SAFEMINDS
coalition was involved in the review of the different phases of the CDC
study currently under web review.

Unfortunately, at no time were the SAFEMINDS individuals involved in review
of this document, neither were any presumed recommendations by SAFEMINDS
ever enacted. This is based on a conversation I had with Lyn Redwood,
President of the SAFEMINDS organization (3/23/04). In fact, concerning the
CDC study, Ms. Redwood was quoted as follows in Insight on the News -
National Issue: 12/23/03 CDC Study Raises Level of Suspicion:

Lyn Redwood, a registered nurse, mother of an autistic child and president
and cofounder of www.SafeMinds.org (Sensible Action for Ending
Mercury-Induced Neurological Disorders), a nonprofit organization dedicated
to ending devastation caused by the needless use of mercury in medicines,
tells Insight that "there are so many problems with the study, but over
time you can see how all the manipulations of the data slowly bring down
the signals for neurological disorders. I think they were trying to get
lower numbers. It must be very hard to admit that a program that was
designed to eradicate infectious disease has resulted in an epidemic of a
whole new kind of disease. But to think that we weren't given a choice when
the regulators and manufacturers knew these products contained mercury is
inconceivable."

Redwood says with a sigh, "On a scale of one to 10, I give the CDC study a
big fat zero. I think it started out good, but when they saw the early
numbers it scared the hell out of them. I don't have any faith in the CDC
doing a decent study of this matter. It's like having the tobacco industry
monitor cigarettes for safety. From a parent's perspective and from a
health-care professional's perspective it's maddening that we can't get
products that are safe, and yet we're forced by law to use them. They need
to just get the thimerosal out. It's barbaric." (Insight on the News -
National Issue: 12/23/03 CDC Study Raises Level of Suspicion By Kelly
Patricia O Meara)

Thus, the information that Dr. DeStefano and Dr. Rhodes posted on the
Pediatrics P3R website on 3/2/04 (in response to Dr. Mark Geier's
peer-reviewed comment) is false. I would like to give the investigators the
benefit of the doubt and say that this misstep was merely an error, but
unfortunately, it is completely clear that this misrepresentation was
intentional. Given the track record of this publication and the evident
gross institutional and commercial conflict of interest, it would be best
if the entire submittal were withdrawn as soon as possible.
 
*******
http://pediatrics.aappublications.org/cgi/eletters/112/5/1039#747

Safety of Thimerosal-Containing Vaccines -- Response to Geier, et al 2
March 2004
    
Frank DeStefano,
Medical Epidemiologist
Centers for Disease Control and Prevention,
Philip H. Rhodes
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Re: Safety of Thimerosal-Containing Vaccines -- Response to Geier, et al


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 To the editor:

The Centers for Disease Control and Prevention (CDC) and all the co-
authors stand behind the science and findings of the study, "Safety of
Thimerosal-Containing Vaccines: A Two- Phased Study of Computerized Health
Maintenance Organization Databases" (1). Although Geier and Geier try to
discredit the study by impugning the integrity of the investigators, they
have identified no substantive deficiencies with the study's methods,
analysis, or results (2).

Their only substantive comment was about possible inaccurate coding of the
thimerosal content of one DTaP vaccine that did not contain thimerosal. We
grant that Table 1 in the manuscript could be interpreted as indicating
that we may have ignored thimerosal-free vaccines, but this was not the
case. We did not make assumptions about the thimerosal contents of the
vaccines. We used documented information on vaccine type and manufacturer
to determine the thimerosal content of specific vaccines. The table was
meant to illustrate the most common combinations of vaccines and amounts of
(estimated) mercury received at several ages. There were a vast number of
possible vaccine combinations adding up to various amounts of mercury at
different ages. A complete table of all possibilities would have been
unwieldy for a journal article.

The two major vaccines containing DTP, DTaP, HiB or HepB that were
mercury-free were the GlaxoSmithKline (GSK) DTaP (HMOB only) and a Merck
Hib-HepB combination (HMO A). Both became available late in the study and
did not constitute a major portion of vaccines received in the first 7
months of age except for the latter portions of the birth cohorts. There
were some additional vaccines used at HMO B in the context of clinical
trials that were thimerosal-free, although the numbers of children involved
were very small. All of these vaccines were assigned a mercury content of
zero in the calculations of cumulative mercury exposure in our study.

At all times throughout the conduct of our study we looked for comparisons
that would involve well-vaccinated children who had received vaccines with
different amounts of thimerosal. The use of a thimerosal- free DTaP
produced by GSK was one of several such potential opportunities. However,
as noted above, in this instance the number of children and amount of
follow-up time involved was insufficient to allow for a useful separate
analysis. Our paper did, however, feature the results of another
opportunity of this kind, i.e. the switch in usage at HMO B from separate
DTP and HIB vaccines to a combined DTPHIB vaccine (1993) and then back to
separate DTaP and HIB vaccines (1997) (1, Appendix Table 3). These results
indicated that the children receiving the larger amounts of thimerosal did
not have a higher risk of developmental delays.

The Geiers question the appropriateness of Dr. Verstraeten's involvement in
the study because he was employed by GSK after he left CDC. Dr. Verstraeten
worked at CDC during the critical time when the study was designed and the
data were analyzed. Once he began working at GSK, his involvement in the
study was limited to reviewing drafts of the manuscript. After he left CDC,
he did not have any further access to the data and was not involved in any
subsequent data analyses.

The Geiers express concerns about the deliberations that CDC held with
outside consultants at the Simpsonwood retreat center to review preliminary
study results. In addition to the Simpsonwood review, the study underwent
extensive review internally at CDC, by external organizations including
representatives of SafeMinds, by an Institute of Medicine (IOM) committee,
and by peer reviewers for Pediatrics. Following many helpful suggestions
from other scientists, researchers, and organizations, improvements were
made in the databases, research methods, and statistical procedures used to
analyze the data. It is accepted and sound scientific practice, especially
with complex and important research issues, to seek and use the advice and
recommendations from both internal and external reviewers to strengthen a
study as much as possible before publishing a final paper. In this case,
four major improvements were made as a result of the reviews of preliminary
findings:

. The methods used to analyze the data were refined and improved.

. Errors in the data (e.g., mistakes in medical records, errors regarding
the thimerosal content of certain vaccines) were corrected to make the
results more accurate.

. Suggestions by reviewers were incorporated into the analysis to address
and reduce potential biases (e.g., differences in health care seeking
behavior among parents that could lead to some children going to their
physician more often and therefore being diagnosed more often).

. More children with diagnoses of interest were identified as the study
progressed and the children at the HMOs became older.

The Geiers mention that they have done an analysis of VSD data and found an
association between increasing doses of thimerosal and neurodevelopmental
disorders. We are not able to comment on this assertion since the study has
not been published and they provided no data in support of the statement.
Perhaps they may be referring to an analysis that they presented at an IOM
Immunization Safety Review Committee meeting on February 9, 2004 in which
they compared risk of autism between children who received
thimerosal-containing and thimerosal-free DTaP vaccines (3). Our analysis
of the same data, however, indicated that the Geiers' results can be
explained by confounding by age rather than any true risk (4).

The Geiers' analyses of the Vaccine Adverse Events Reporting System (VAERS)
and U.S. Department of Education data contain numerous conceptual and
scientific flaws, omissions of fact, inaccuracies, and misstatements that
are detailed in an extensive critique by the Academy (5). The other studies
mentioned by the Geiers that measured hair mercury levels, urinary mercury
excretion, and in-vitro toxicological effects of ethylmercury may have
relevance to the biological plausibility of the hypothesis that
thimerosal-containing vaccines could be associated with neurodevelopmental
disorders. Some of this evidence had been reviewed in 2001 by the IOM
Immunization Safety Review Committee, which concluded at that time that the
hypothesis was biologically plausible (6). The more recent studies
mentioned by the Geiers were also reviewed at the IOM Immunization Safety
Review Committee meeting on February 9, 2004. We will be interested to see
how the committee interprets these studies and their implications for the
possible association between thimerosal-containing vaccines and
neurodevelopmental disorders, including autism.

Finally, the Geiers take issue with our interpretation that possible
encephalopathy from whole-cell pertussis vaccines would occur too
infrequently to have had a material impact on our results. The most
comprehensive review conducted on this topic by IOM found that the risk for
acute encephalopathy after pertussis vaccination was at most 10.5 per
million (7). We stand by our conclusion that encephalopathy after pertussis
vaccination is unlikely to have had a meaningful impact on our results.

Sincerely yours,

Frank DeStefano, MD, MPH

Philip H. Rhodes, PhD

References:

1. Verstraeten T, Davis RL, DeStefano F, et al. Safety of thimerosal
-containing vaccines: A two-phased study of computerized health maintenance
organization databases. Pediatrics. 2003;112:1039-1048.

2. Geier MR, et al. Study misses link between thimerosal and
neurodevelopmental disorders. Pediatrics - P3Rs for Verstraeten el al.,
112:1039-1048.

3. Geier MR, Geier D. Autism and thimerosal-containing vaccines: analysis
of the Vaccine Adverse Events Reporting System (VAERS). Immunization Safety
Review Committee Meeting 9: Vaccines and Autism. The National Academy of
Sciences, Washington, DC, February 9, 2004.

4. Davis RL. Vaccine Safety Datalink Study: Autism Outcome. Immunization
Safety Review Committee Meeting 9: Vaccines and Autism. The National
Academy of Sciences, Washington, DC, February 9, 2004.

5. Study fails to show a connection between thimerosal and autism. American
Academy of Pediatrics 2003.
(http://search.aap.org/aap/CISPframe.html?url=http://www.cispimmunize.org/pr
o/doc/Geiersummary.doc)

6. Stratton K, Gable A, McCormick MC, eds. Thimerosal-Containing Vaccines
and Neurodevelopmental Disorders. Institute of Medicine. Washington, DC:
National Academy Press; 2001.

7. Howson CP, Howe CJ, Fineberg HV, eds. Adverse Effects of Pertussis and
Rubella Vaccines. Institute of Medicine. Washington, DC: National Academy
Press; 1991.
 
******
And response of DeStefano to Brian S. Hooker in first article

The Safety of Thimerosal-containing Vaccines -- Response to B.S. Hooker 26
March 2004
    
Frank DeStefano,
Medical Epidemiologist
Centers for Disease Control and Prevention
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Re: The Safety of Thimerosal-containing Vaccines -- Response to B.S. Hooker


Email Frank DeStefano


 In a previous response to a comment on our article, we stated:

". the study underwent extensive review internally at CDC, by external
organizations including representatives of SafeMinds, by an Institute of
Medicine (IOM) committee, and by peer reviewers for Pediatrics. Following
many helpful suggestions from other scientists, researchers, and
organizations, improvements were made in the databases, research methods,
and statistical procedures used to analyze the data."

The statement is clear that the reviews were conducted during preliminary
stages of the analysis and that the suggestions of a number of reviewers
were incorporated into the final analysis. Ms. Redwood is the President of
SafeMinds. She spent the better part of a day at CDC reviewing preliminary
analyses and results with CDC researchers working on the study. The
analyses of cumulative exposure by 7 months of age in the published
manuscript were included at her request.