Brian Deer's Allegations against Dr Andrew Wakefield: A Rebuttal

Brian Deer's Allegations against Dr Andrew Wakefield: A Rebuttal

Written by a parent of an autistic child.

Introduction

In February 2004 Brian Deer began a campaign to discredit the work of Andrew Wakefield. A series of articles was published in The Sunday Times and Channel 4 broadcast MMR: what they didn't tell you in November 2004. These outlets made several claims which are factually untrue, selective in their use of facts (key facts ignored) and biased. Although this began over four years ago, the campaign made claims that subsequently formed the basis of the General Medical Council's (GMC) investigation of Dr Andrew Wakefield, Professor John Walker-Smith and Professor Simon Murch.

The GMC allegations are similar to Deer's. However he has never revealed to Sunday Times readers his role in furnishing the GMC with the allegations. By the same token the GMC does not reveal the identity of the complainants. In effect complainants, whatever their motivation, can make damaging charges against doctors under veil of anonymity; whether patients or representatives of the pharmaceutical industry. The allegations concern research at the Royal Free Hospital (RFH) in the late 1990s and in particular a paper published in The Lancet in February 1998, and for Wakefield alone, research in support of autistic children seeking damages from MMR/MR manufacturers.

The following rebuttal draws largely on information in the public domain and has been drafted ahead of the conclusions the GMC's fitness to practice hearing will reach in 2009. Given the public prominence of Deer's allegations it is important they are now rebutted.

Deer makes the following claims:

Х In 1998 The Lancet published a paper by Wakefield et al which claimed MMR causes autism and bowel disease (AJ Wakefield et al, СIleal-lymphoid-nodular hyperplasia non-specific colitis, and pervasive developmental disorder in children', The Lancet , Vol. 351, 28 February 1998)

Х Wakefield did not disclose in The Lancet his work on behalf of autistic child claimants litigating against MMR manufacturers

Х Wakefield and the Royal Free started a scare that MMR causes autism and bowel disease

Х Wakefield advocates the use of single vaccines instead of MMR against government policy

Х The 1998 Lancet paper was methodologically flawed

Х Wakefield used invasive procedures involving scopes of the children's bowels and lumbar punctures

Claim 1: Brian Deer states incorrectly that Wakefield et al's 1998 Lancet article claims MMR is linked to autism and bowel disease. It does not. Rather the article identifies an association between bowel disease and autism Ц an entirely different finding.

His article in The Sunday Times of 22 February 2004 contains several paragraphs referring to:

Х Сthe alleged link between measles, mumps and rubella vaccine and autism in young children' as the Lancet paper's Сfindings' (para 2)

Х Сresearch claiming a link with autism' (para 3)

Х Сfindings linking MMR and autism' (para 4)

In fact the abstract summarising the paper's main findings does not mention an MMR-autism link. Instead it says СWe identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers' (p.637).

The main purpose of the paper was to report the presence of bowel disease in 12 autistic children. The mention of an MMR-autism link is a subsidiary part of the paper and is expressly treated in hypothetical terms requiring Сfurther investigations' (p. 641). For example, it summarises the prior environmental exposures which the parents and children's doctors reported as associated with the onset of autism. In 8 out of 12 children this environmental exposure was MMR. For the other 4 children, parents/doctors of two referred to measles and otitis media and two were unable to identify an exposure. The summary is simply what the parents reported, which the researchers were duty bound to report given the paper's terms of reference. Such temporal association between autism and MMR is not presented as causal. The paper clearly states that it Сdid not prove an association between measles, mumps, and rubella vaccine and the syndrome described' (p. 641).

The distinction between the principal factual findings (the presence of bowel disease in the autistic children) and a subsidiary hypothesis requiring further research (a putative link between MMR and autism and bowel disease) is fundamental to the paper (as it is to other scientific papers recommending further research into hypotheses beyond published findings). Deer does not refer to the principal purpose of the 1998 paper, to show findings of bowel disease in autistic children, and elevates a subsidiary hypothesis, for which no evidence is given, to the principal finding.

Despite the authors' express denial of a proven link, Deer (para 13) goes on to make a judgement of the paper, that it Сcontained no scientific evidence of a link with MMR, only the УassociationФ made by parents'. That is precisely what the paper said; yet Deer treats this finding as his revelation in the face of his mistaken reading of the paper that it claimed a link between autism and MMR.

Although The Sunday Times' articles repeatedly refer to the editor of The Lancet , Richard Horton, as stating when interviewed on 21 February 2004, that the 1998 paper was СФfatallyФ flawed', they never quote the editors of The Lancet's more temperate statement issued on Friday 20 Feb Ц ahead of The Sunday Times' first article on 22 February Ц that Сwe do not judge that there was any intention to conceal information or deceive editors, reviewers, or readers about the ethical justification for this work and the nature of patient referral'.

Claim 2: : On 22 February 2004, Deer claimed in The Sunday Times that УAndrew Wakefield, the doctor who champions the alleged link between measles, mumps and rubella vaccine and autism in young children, stands discredited for misleading his medical colleagues and The Lancet, the professional journal that published his findings. The investigation has found that when he warned parents to avoid MMR, and published research claiming a link with autism, he did not disclose he was being funded through solicitors seeking evidence to use against vaccine manufacturersФ. ( paras 2 &3)

The Sunday Times has now established that four, probably five, of these children were covered by the legal aid study. And Wakefield himself had been awarded up to г55,000 to assist their case by finding scientific evidence of the link. ( para 9)

The Lancet paper was an СEarly Report' case study based on clinical findings from 12 children treated by the RFH between 1996 and 1997 who were diagnosed with autism and symptoms of bowel disease. Whatever hypothesis the authors held about a link between autism and MMR, the paper does not present this hypothesis as fact.

For the authors the paper's express purpose was to present findings of an autism/bowel disease link which justified further research, presumably with larger samples and controls. Its purpose lay outside Wakefield 's own interest in advising claimants in the MMR litigation. Presumably, in the light of the paper's principal findings of an autism/bowel disease link, Wakefield did not disclose his other interests when submitting it to The Lancet . This would have been a matter for his judgment. The GMC on the other hand insists that it should have been clear to Wakefield that others would have perceived the paper as involving a conflict of interest. But this can only be claimed if the subsidiary hypothesis is elevated to the main purpose of the paper and the principal findings of an autism/bowel disease link ignored.

However to set the record straight Wakefield revealed his involvement in litigation research by letter in The Lancet on 2 May 1998. Deer does not mention this. Whilst Deer obsesses about Wakefield 's failure to disclose in the February 1998 article, he ignores the convention at the time for medical scientists rarely to disclose potential conflicting interests. Even in the early 2000s this was rare. Between 2000 and February 2004, when Deer first published his allegation, we have been unable to find a single disclosure among all the publications we have found of the 32 expert witnesses for the defendant manufacturers in the MMR litigation. Nor does Deer address the extent to which medical scientists conducting parallel research for pharmaceutical companies fail to disclose this in papers published in academic journals.

Further, despite Horton's statements to the contrary, the GMC hearing has seen correspondence between Richard Barr, the solicitor representing the MMR children, Richard Horton and The Lancet staff in 1997, one year before The Lancet paper was published, which clearly disclosed Wakefield 's role in legal aid research.

Deer further suggests that at the time of publication one-third of the children in The Lancet paper were litigants in the action against MMR manufacturers. However he fails to publish in The Sunday Times the dates when each of the children started litigation in relation to dates they were selected for the study. The children were patients at the Royal Free in 1996 when they were enrolled in the research. The research was given ethical approval in December 1996 and analysis of data began in 1997. The children were selected by Professor John Walker-Smith, the most senior researcher, who stated to The Lancet , following Deer's Sunday Times report, that the children were selected on a chronological basis, i.e. the first to be admitted as patients were the first to be selected Ц a conventional method of selection for small case studies. The paper says the children were Уconsecutively referred to the department of paediatric gastroenterologyФ.

The fact that some of the parents of the 12 children went on to start litigation against MMR manufacturers after their children were admitted to the RFH is a decision entirely for them and not one they were duty bound to inform The Lancet study about. There is an important issue of human rights that Deer and the GMC ignore: the right of parents of severely disabled children who suspected their children were damaged by MMR to seek compensation through the courts. The parents have a right Ц even a duty Ц to protect their children's interests in the face of a lifelong condition for which there is no cure. The temporal link between MMR and autism and other symptoms was the basis for a legitimate suspicion that required scientific research to establish the validity and nature of the link, a link in time which many parents of autistic children Ц not only the 1,500 litigant parents Ц attest to. In the absence of clinical research financed by government, the task of establishing the link lay with the litigant parents themselves.

These parents are entitled to engage in litigation. Would Deer have them delay litigation for several years until after the research is published, so denying themselves their right to litigate, or that Wakefield should remove all litigants from his Lance t research? Deer's (and the GMC's) view of medical research appears to be that research subjects should be powerless political subjects Ц a view that is questionable and certainly inappropriate in the case of children who because of severe disabilities have good reason to pursue their rights.

Claim 3: Dr Wakefield and the Royal Free Hospital started a scare that the MMR caused autism and bowel disease as a result of Wakefield publishing the 1998 Lancet paper and the Royal Free's press conference on the paper both in February 1998.

УDispatches reveals what parents were never told. How a major London teaching hospital and Dr Andrew Wakefield launched a health scare which questioned the three in one MMR vaccine.Ф (Dispatches - MMR: what they didn't tell you, Channel 4, Thursday 18 November 2004 )

In fact, the fall in MMR take-up began a year after it was introduced in the UK in 1988. In 1989/90 the numbers of children who completed the primary series of vaccination was 1,396k. This number fell to 1,069k in 1990/91 and to 561k in 1996/97 (УNHS Immunisation Statistics, England : 1997-98Ф, Dept of Health, Table 5 Completed Primary Course, 1989 to 1997-98, p.9). The uptake of primary MMR had fallen by 60% before the Wakefield paper was published in 1998.

One public Сscare' that contributed to a fall in MMR take-up was concern over the Urabe mumps strain in the early 1990s whereby a number of children in the UK contracted meningitis from the mumps component of the Pluserix and Immravax brands of MMR available at the time. In fact months before the UK vaccine authorities decided to introduce Pluserix and Immravax in 1988, the Canadian government had already withdrawn them because of the dangers associated with the Urabe strain. The minutes of the UK Joint Committee on Vaccination and Immunisation for May 1987 show that the decision to introduce MMR in 1988 was made in the full knowledge of this. In 2006 parents in Japan won an action against the government for damages caused to their children by the mumps component of the MMR.

Claim 4: At the Royal Free press conference to launch The Lancet paper, Dr Wakefield advocated the use of single vaccines instead of the MMR.

Andrew Wakefield is quoted as saying , У the single vaccines in this context is saferЕgiving the measles vaccine on its own reduced the risk of this particular syndrome developing.Ф Dr Wakefield believes that the MMR should be broken up into single vaccines . ( Dispatches , MMR: what they didn't tell you, Channel 4 , 18 November 2004)

Dr Wakefield gave this reply to a question from a journalist at the press conference held by the Royal Free Hospital in February 1998 to dispel suggestions that the paper was anti-MMR.

In 1998 the government provided free on the NHS both single vaccines for mumps, measles and rubella and the combined MMR. The government removed access to the former in 1999 having provided a choice between the multivalent and single valiant vaccines since MMR was introduced in 1988. Dr Wakefield was therefore voicing a viewpoint clearly within the scope of government's policy to provide choice of combined MMR or single vaccines.

Claim 5: Because the 1998 Lancet paper used a small sample of 12 child patients its findings are unreliable.

УIn Feb 1998, Dr Wakefield and his colleagues published their findings in a leading medical journal. Described as an СEarly Report', the study was tiny, just 12 case histories and Dr Wakefield claimed that in just eight cases, parents had blamed MMR. Despite shortcomings in the paperЕФ ( Dispatches , MMR: what they didn't tell you, Channel 4 , 18 November 2004)

The study of 12 children was published under The Lancet 's СEarly Report' section and was therefore based on a small sample not intended as a representative sample, which The Lancet's readership would have understood. The paper was subject to rigorous peer-review by anonymous experts.

The children were part of a case series and according to the paper Сconsecutively referred to the department of paediatric gastroenterology' at the Royal Free Hospital (p.637). They were not part of a random sample. As an СEarly Report', the paper makes clear that the findings reported are not conclusive, but subject to further research.

Wakefield and colleagues went on to publish further papers using much larger samples. The publication of a small pilot study is a legitimate part of developing research leading to larger studies.

Claim 6: Wakefield used unnecessary invasive procedures in his research Ц i.e. bowel scopes and lumbar punctures Ц on the child patients.

Parents of the child patients in The Lancet paper have reported the extent of their children's gastric symptoms, reflecting the wider experience of autistic children with bowel disease. The symptoms include constipation alternating with diarrhoea, faecal impaction, intestinal dysmotility and abdominal pain. The use of endoscopy was based on clinical need. Likewise the use of lumbar punctures for some of the children was dictated by their neurological symptoms. These tests were used to support diagnosis and treatment and the findings contributed to The Lancet paper. The suggestion that these investigative procedures are not necessary is part of wider attempt to demote the seriousness of the children's symptoms and to deny or withdraw treatment. More needs to be said about these serious medical developments.

Conclusion

On the basis of the evidence presented to date it seems highly unlikely that the GMC will find against Wakefield and his two colleagues, Professors Simon Murch and John Walker-Smith. However, It is also worth considering the possible outcome for autistic children if The Sunday Times and Deer's campaign is successful and the GMC finds against the doctors.

Х Wakefield 's research programme of investigating the role of MMR in autism and associated enterocolitis could end.

Х Doctors and scientists in the UK could be put off doing research that might lead to questioning the safety of MMR or other vaccines. In effect parents deciding whether to vaccinate their children would have only the safety claims of manufactures and government to rely on. There would be no alternative, independent scientific assessment of vaccine safety they could consider. An important area of independent medical research could end. The core ethic of independent science would be damaged by government and GMC inference on a scale rarely seen in Western democracies.

Х Autistic children exhibiting symptoms of bowel disease Ц e.g. constipation alternating with diarrhoea, faecal impaction, intestinal dysmotility and abdominal pain Ц may no longer receive treatment. Many children are already denied treatment.

Instead of conducting clinical research to replicate or disprove Wakefield 's findings, the UK government and medical establishment have engaged in personal attacks and produced epidemiological research that fails to address Wakefield et al's clinical evidence. Without precedent in medical history, Prime Minister Tony Blair and John Reid, then Secretary of State for Health, personally criticised Wakefield in February 2004, with Reid encouraging the General Medical Council to investigate Wakefield, who was subsequently charged with professional misconduct, along with two of his former colleagues from Hampstead's Royal Free.