Simon Murch statement states that Lancet study was same as 172/96 investigations

This page is research from an award-winning investigation, concluding in 2011, by Brian Deer for The Sunday Times of London into a campaign linking the MMR children's vaccine with autism based on fraudulent research by British former doctor Andrew Wakefield

Responding to Deer's investigation, the statement below was issued through the Lancet on February 20 2004 by Simon Murch, who with Andrew Wakefield and John Walker-Smith would in 2007 face charges at the UK General Medical Council, where Murch would repudiate this statement, argue that it was almost wholly wrong and claim that the work described was purely a clinical case series


These allegations concerning our 1998 study are extremely serious, and clearly require immediate clarification. I welcome the opportunity to do so. My comment relates to the alleged lack of Ethical Practices Committee approval. I refute the allegation absolutely on the basis of extensive documentary evidence.

The protocol for the 1998 Lancet paper was submitted on September 16, 1996, to what was then termed the Ethical Practices Sub-Committee. It was entitled “A new paediatric syndrome: enteritis and disintegrative disorder following measles/rubella vaccine”. It was signed by Andrew Wakefield as lead investigator. Named consultants were John Walker-Smith and myself, with signed collaborators Peter Harvey, for the department of neurology, and Mark Berelowitz, for the department of child psychiatry. The application was initiated due to findings at colonoscopy of two children with behavioural disorders, which would now be classified within the autistic spectrum, and a history of chronic gastrointestinal symptoms, and recognition of a broadly similar clinical history among other referred patients. Specifically, for several years previously we had looked after an autistic child with severe ulcerative colitis who eventually required colectomy (not included in the study), and the second child colonoscoped (on September 2, 1996) had ileitis of sufficient extent that a diagnosis of probable Crohn’s disease was made. Following this diagnosis, the child had been entered in good faith by our inflammatory bowel diseases fellow into an ongoing (ethically approved) study of polymeric enteral nutrition. He had already made remarkable symptomatic improvement, including apparent cognitive advance. We, thus, appeared to be dealing with a condition of significant severity, and had seen clinical improvement unprecedented in this child’s history. News of this improvement was rapidly disseminated among parents of autistic children, which I believe led to many further referrals. This child was included in the study, with additional investigations performed after ethics approval was obtained.

The title of this submitted application is a point of contention, and should be clarified. Having taken initial advice from our psychiatric colleagues on the basis of referral letters, it was considered that these children demonstrated a form of autism called disintegrative disorder (Heller’s disease). After full psychiatric assessment of each child seen, it was later concluded that the more accurate description for the submitted paper should be pervasive developmental disorder. Our working title for these cases had, however, remained disintegrative disorder, while some parents referred to their child as autistic, and others did not. The whole area of nomenclature in autistic spectrum disorders was notably difficult at that stage. As we saw more patients, we moved towards a more inclusive label of autism, which was used in subsequent correspondence after February, 1998, to the Ethical Practices Committee. Measles and rubella were singled out in the application since these conditions, but not mumps, had been linked to autism in previous isolated reports.

This application (172-96) was for permission for in-depth analysis of 25 patients, referred either by general practitioners or the vitamin B12 unit at the Chelsea and Westminster Hospital, who had been studying B12 absorption in children with regressive neurological disorders. The selection criteria explicit in this application were the presence of disintegrative disorder, symptoms and signs suggestive of gastrointestinal disease, and parental request for investigation. All patients reported met these criteria. The consultant paediatricians responsible for the children’s care decided on the investigations, although advice was taken from colleagues at other centres. We determined that these investigations were required clinically, not only to characterise gut inflammation but also to exclude primary neurological diseases. We had in particular taken advice for the neurological investigations, since some of the referrals appeared to have suffered an encephalitic illness, and specifically the inclusion of lumbar puncture was suggested to us as important for assay of cerebrospinal fluid lactate, to exclude mitochondrial cytopathies that can cause both neurological regression and bowel disease. Several of these cases had not been investigated to exclude a primary cause of their regression, and we thought it important to ensure that we were not missing underlying metabolic or genetic abnormality. Proposed investigations thus included ileocolonoscopy and upper endoscopy, barium follow-through if ileitis was identified, lumbar puncture (if sufficient fluid remained after lactate assay, serology and/or cytokine testing would be performed), magnetic resonance imaging of the brain to exclude structural defects, electroencephalography to exclude covert epilepsy, electrophysiological testing, and a panel of standard laboratory tests, with isolation of DNA for complement genotyping, since C4 deficiency had been reported to be an association.

The protocol was referred back at first submission in November, 1996, with clarifications and amendments suggested, and was approved in December, 1996. This protocol formed the basis for all children investigated in the 1998 Lancet paper, and all were investigated. We had no idea at the time of our Ethical Practices Committee application that lymphoid hyperplasia would prove so common, although it was a prominent part of the final report.

It is important to document where the protocol differed from the submission. First, neither I nor my fellow endoscopist, Mike Thomson, eventually considered it justified to perform upper gastrointestinal endoscopy in most patients—there was then no published evidence of upper gastrointestinal pathology, and we were performing these procedures under sedation, as was then our practice. Getting the precise level of sedation is not easy in children with such behavioural difficulties, and we felt this was not appropriate at that time, although our policy altered in later years. Second, in the event, we did not continue with this extended protocol for the full 25 patients, again because of the clinical concerns of myself and my colleagues, since we had found no evidence of underlying metabolic abnormality in any case and did not consider that lumbar puncture of further cases was indicated. Other children subsequently seen were thus not subjected to this extended protocol, and investigated by testing of inflammatory markers and abdominal X-ray, with endoscopies performed if thought clinically indicated, unless there were clear clinical reasons to perform additional tests.

Following the publication of the initial report, John Walker-Smith sought guidance from the Ethical Practices Committee about further investigation of future cases, stating “I would like formally to request Ethical Committee approval for our clinical research analysis of these children who we are continuing to see by clinical need”. In a letter to the ethics committee, further studies were referred to under the title “autism and non-specific colitis and Lymphoid Nodular Hyperplasia” since that was the clinical entity that the earlier study had defined. This was reviewed on July 22, 1998, and data collection from clinically indicated investigations was approved. This was for study of subsequent patients investigated on the basis of gastrointestinal symptoms and initial assessment, and in no way relevant to the 1998 Lancet paper, which had been conducted entirely according to the 1996 approval. Thus, there was no change in the name of the ethical approval requested for the 1998 paper, as mistakenly alleged.

A local review initiated by the Royal Free medical school in July, 1998, confirmed that the application had been fully considered by the ethics committee, and that assurance had been given that the investigations were clinically indicated. It was also apparent that the continuing investigation of those children had been reviewed by the ethics committee in July, 1998, and appreciated that investigation of children seen after publication had become less extensive, and usually restricted to gastroenterological testing as thought clinically appropriate.

We contended then, and still contend now, that these were standard and appropriate gastroenterological and neurological investigations for the symptoms reported given the current state of knowledge at that time. Undoubtedly we now perform endoscopy less frequently, but that is based on extensive experience. Similarly, a child with coeliac disease in the 1970s would have had three diagnostic biopsies compared to the one, or even none, now performed.

Thus, I can confirm that the patients presented in the Lancet study were investigated in accordance with the ethics committee approval of December, 1996, and that no attempt was made to seek retrospective approval.

Dr Simon Murch

Senior Lecturer and Consultant in Paediatric Gastroenterology, Royal Free and University College Medical School

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