PRIVATE EYE 5 March - 18 March 2004
MMR INTERESTING CONFLICTS
 
The vilification of Dr Andrew Wakefield in recent days has been a side show
to the important issue of whether the mumps, measles, and rubella triple
vaccine (MMR) poses a risk to a small sub set of children. But the attacks
have served a purpose. They have highlighted the need to preserve
independent medical research - and reminded the public that there is one
rule for an off-message messenger like Dr Wakefield and quite another for
the government and drug companies.
 
For example, one leading health official responsible for immunisation has
been working as an expert for the three defendant drug companies in the UK
MMR court case since July 2002. Yet as far as the Eye can ascertain, she
has never declared that potential ''conflict''  on any of her research papers.
 
Dr Elizabeth Miller, head of immunisation at the government''s Health
Protection Agency (HPA), last year alone published three papers in the
Archives of Disease in Childhood directly related to the MMR controversy.
One suggested that the combined triple live virus does not overload the
immune system, so there is no need for single vaccines. Two others
suggested that parents have been more likely to attribute their children's
autism to MMR since 1998, when Dr Wakefield and his team at the Royal Free
hospital in north London published their controversial paper.
 
Nowhere on Dr Miller's papers does she declare that she is also an expert
witness for the drug companies GlaxoSmithKline, Aventis Pasteur and Merck.
 
Moreover, the Eye has begun trawling through scientific and medical
journals to examine papers published over the last two years by other
defendant drug company experts. So far we have not found a single
declaration on any paper that the author also acts as an expert for the
defendant drug companies - even though at least two of the experts (Dr
Diane Griffin, an American, and Professor Volker ter Meulen, a German),
have produced research papers directly associated with vaccination.
 
Unlike in the case of Dr Wakefield, there have been no screaming headlines
attacking their credibility or honesty; no demands for an inquiry by the
General Medical Council; no snipes at their ''fatally flawed'' research.
 
Instead, such authors continue to enjoy the support of government and big
business. By contrast, Dr Wakefield only has the support of harrassed
parents who believe their children were damaged by MMR, and, until
recently, the impoverished Legal Services Commission - hardly powerful or
influential.
 
Dr Miller maintains that neither she nor her department was paid by the
three pharmaceutical companies for the detailed and lengthy report she
submitted on their behalf to the court last June. She prepared their
evidence in her own time, her department says, and did not declare it on
any papers because there was no financial interest.
 
Nevertheless, it is known that money from those companies finds its way
into the agency, formerly the Public Health Laboratory Service, through
other research channels. In a recent annual report, Dr Miller listed five
''non-personal'' interests - ie payments which benefited her department
rather than herself. Two of the companies featured were MMR defendants.
 
The rules on conflict are weak, open to interpretation and generally not
enforced - so should any criticism not be dished out in equal measure? As
one leading journal states ''examples of potentially conflicting interests
that should be disclosed include relationships that might detract from an
author's objectivity in presentation of study results and interests whose
value would be enhanced by the results presented.''
 
How can Sir Liam Donaldson, chief medical officer, and his deputy
responsible for immunisation, Dr David Salisbury, justify their attacks on
Dr Wakefield for non-disclosure of an interest when their own staff appear
equally compromised? No doubt Dr Miller sought clearance before agreeing to
act for the defendant drug companies. But every time she now opens her
mouth the question arises: Is she speaking from the ''impartial ''view of
the health department, open to all new research that comes to its
attention; or for that of the defendant drug companies? As Eye readers will
recall, Dr Miller also conducted the first ever trial of MMR among 10,000
children before its introduction in the UK nationwide.
 
It is clear the medical establishment and ministers had been waiting for an
opportunity to attempt to discredit Dr Wakefield. Thus they seized on the
Sunday Times's resurrection of a debate about conflict which emerged in the
Lancet six years ago when Dr Wakefield published his controversial 1998
study.
 
Shortly after publication the Lancet carried a letter from Dr Wakefield on
behalf of all the authors in response to suggestions that there may have
been ''litigation bias'' in their paper. It said that Dr Wakefield had
agreed quite separately to evaluate a small number of children on behalf of
the Legal Aid Board.  ''These children have all been seen expressly on the
basis that they were referred through the normal channels (eg. GP, child
psychiatrist or community paediatritican) on the merits of their symptoms.''
 
Nothing about that ''conflict'' has changed but Lancet editor Richard
Horton seemed to panic in the face of more serious - and completely
unsubstantiated - allegations from the Sunday Times about subjecting the
children to invasive procedures without ethical approval and questions
about the Lancet's role in the affair - allegations the newspaper was
forced to ditch.
 
Interestingly, Horton's condemnation of the Royal Free paper as ''fatally
flawed'' ( which gave oxygen to the Sunday Times ''scoop'') was dropped by
the time the Lancet published its statement about the affair the following
week. It stated that it was ''regretful'' that the Lancet had not been made
aware that the parallel legal aid had not been disclosed as it should have
been '' because it would have been material to our decision-making about
the paper's suitability, credibility and validity for publication''. It did
not withdraw the paper or say it was fatally damaged.
 
Of course the issue of potential conflicts of interest - whether by Dr
Wakefield or those acting as experts for the defendant drug companies -
only flags up the possibility of research flawed by bias.  Before a study
can be ''fatally flawed'', as health chiefs maintain Dr Wakefield's is, the
research itself must be shown to be faulty.
 
Aside from the fact that even Horton accepts that the Royal Free team
identified a new syndrome suffered by children with gut disease and autism
( something so scientifically and medically significant, one might think it
worthy of investment and further investigation), that original paper is now
the equivalent of scientific chip wrappings. Science has moved on; and the
Royal Free team  has published more papers detailing the unique pattern of
disease in these children's guts.
 
In both the UK and the US, meanwhile, measles virus, some of it vaccine
strain, has now been found at the site of inflammation in the guts, in the
blood and in the spinal fluid of some autistic children but not in
''normal'' children. Separate studies at Utah State University have found
that some autistic children have auto-antibodies which are attacking the
protein sheath that protects the nerve and brain in those children,
researchers found a higher level of measles virus antibodies and an
''unusual MMR'' antibody, whereas their response to other vaccines did not
differ between autistic and normal children.
 
None of this proves causation or a link; but combined they do provide a
mechanism for brain damage and one potential trigger that might lead to
autism. And that surely needs further investigation.
 
Last week, while some newspapers and the medical establishment queued up to
kick Dr Wakefield, a new US study of children defined as autistic by the US
department of education and the biological surveillance summaries of the
Center for Disease Control found ''a biological plausibility and
epidemiological evidence showing a direct relationship between... measles
containing vaccines and serious neurological disorders''. It also found a
relationship between mercury containing vaccines and neurological
disorders, the subject of litigation in the US. At the top of the study the
authors, Dr Mark Geier and David Geier, both declare a potential conflict
of interest in that they have been expert witnesses or consultants in areas
involving adverse reactions to vaccines in civil litigation.
 
In May last year Dr Miller - in her role as head of immunisation at the
HPA, rather than as an expert for the drug companies - was critical of the
Geiers' earlier work. As indeed was Britain's Committee on Safety of
Medicines, which found ''serious methodological'' flaws. But as the Daily
Mail and other newspapers reported last week, that committee and the Joint
Committee on Vaccination and Immunisation is packed with experts who either
have shares in the defendant drug companies, receive funding for research
from them or are paid advisers to them.
 
As the Eye reported in 2002, three of the members who sat on the Medical
Research Council's review of the ten-fold rise in autism were advisers to
the defendant drug companies. Even the chair had shares in one of the
companies.
 
The point is that potential conflicts of interest are common in medical and
scientific research and development and Dr Wakefield's is but a puff in the
wind. Ninety percent of research depends on big business and the
pharmaceutical companies - and this is set to rise. The big companies
already have a direct line to the prime minister through the Pharmaceutical
Industry Competitive Task Force (PICTF), which Tony Blair set up after a
meeting with the heads of AstraZeneca, GlaxoWellcome and SmithKlineBeecham.
 
The companies have already stated that they see the NHS as a huge
unexploited resource. And the government's own reforming NHS Plan 2000
states that; ''The pharmaceutical industry is a UK success story, employing
over 60,000 skilled workers and maintaining an annual trade surplus of over
2 billion. The industry is also the UK's leading investor in research and
development. The NHS has a major role to play in ensuring that the UK
remains an attractive base for the industry.''
 
Hence it has set about removing barriers to big business in the drug
industry, encouraging hospitals and universities to enter into joint
ventures and create mini-companies to exploit their research. They will
inevitably become even more dependant on drug company influence - and even
more at risk of serious conflicts of interest.  Yet no one is shouting
about that.