Dr Andrew Wakefield, the researcher who is the leading proponent of a link between autism and the measles, mumps, and rubella vaccine (Lancet 1998;351: 6379500320), was accused last week of conducting investigations on children without the proper approval of his hospital's ethics committee. The ethics committee of the Royal Free Hospital, London, where Dr Wakefield worked, was also criticised for the procedures it adopted.
Dr Evan Harris, Liberal Democrat MP for Oxford West and Abingdon, who sits on both the BMA's ethics committee and the House of Commons Science and Technology Committee, made the allegations during an adjournment debate in the House of Commons (House of Commons Official Report (Hansard) 2004. March 15: cols 128-36).
Speaking about the work done at the Royal Free Hospital by the inflammatory bowel disease group between 1995 and 1998, Dr Harris said: “There is very clear evidence pointing towards unethical conduct by the researchers—or by one or some of them—and equally strong evidence of failure and incompetence by the research ethics committee.”
He said that documents uncovered by the journalist Brian Deer, who recently exposed the fact that Wakefield had not declared a payment from the Legal Aid Board for his work (Sunday Times, 2004. February 22: 1, 12, 13), raised “doubts and allegations about whether children were exposed to unacceptable risks and unnecessary procedures.” Dr Harris said: “In the scandal over Dr Andrew Wakefield's failure to declare financial and conflicts of interest when his research group's article was published in the Lancet six years ago, the welfare of the children who were his research subjects seems to have been forgotten.
“In 1996, and subsequently, researchers in the inflammatory bowel disease study group subjected children to a battery of invasive tests.” These included upper gastrointestinal endoscopy, ileocolonoscopy, and lumbar punctures, he said. “Those procedures are not trivial on consenting adults, let alone autistic children, who must be heavily sedated or even anaesthetised.”
Figure 1.
Dr Evan Harris wants an inquiry
Credit: UPPA/TOPFOTO
Dr Harris said that guidelines from the British Paediatric Association (now the Royal College of Paediatrics and Child Health), the General Medical Council, and other bodies at the time laid down that research where there was no likely clinical benefit to children should not involve anything worse than a blood test, and that prior approval from an ethics committee was necessary.
Dr Harris's criticisms centred on two points. Firstly, when Dr Wakefield and his colleagues submitted the trial protocol for ethics approval in 1996, they said that the study was to investigate enteritis in children who had a condition known as “disintegrative disorder,” also known as disintegrative psychosis or Heller's disease. But the published research showed that not one of the 12 children investigated had disintegrative disorder; they were mostly children with autism.
Dr Harris said that the researchers' possible justification for carrying out lumbar punctures on the children applied only to children with disintegrative disorder, because in a few cases the disorder could be caused by a metabolic disorder that could be detected by looking at the cerebrospinal fluid.
It appears that when the selection criteria for the investigated children changed to include a wider group—those with autism—the research ethics committee was not informed of the significant change in protocol, nor was its approval sought.
The second criticism concerned the alleged lack of scrutiny given to the research proposal by the Royal Free Hospital's ethics committee. Although the committee granted prior approval for the research, this was on the basis of investigations being carried out for diagnostic or therapeutic purposes.
Dr Harris said that, according to documents released to the Sunday Times by the strategic health authority, the ethics committee did not seem to have asked an independent outside expert “whether the battery of tests could be considered of therapeutic value to the children.”
When concerns were raised about the project after publication of Dr Wakefield's work in 1998, the ethics committee's chairman said that the committee had not thought it necessary to give approval for the invasive investigations because the children would have been having these investigations anyway for diagnostic, not research, purposes.
He said: “In fact, after publication of the paper, the research ethics committee tried to claim that it was not even its job to make a judgment about whether procedures were in the children's best interests.”
Dr Harris concluded by saying that the government should order an independent inquiry.
A spokeswoman for the Royal Free Hospital issued the following statement: “As has been stated before, the study in question was approved by the ethics committee after rigorous ethical analysis and we believe that the investigations were appropriate for the children concerned. Its [the committee's] decisions were then and are now independent of both [London] university and the trust.”
A statement from Andrew Wakefield and neurologist Peter Harvey, who was one of the authors of the Lancet paper, said: “Autism and disintegrative disorder are clinically indistinguishable and disintegrative disorder is a form of autism in which the child develops normally and then regresses. This is what we observed in the children in the 1998 paper and subsequently.”
Documents relating to the case can be found on Brian Deer's website at www.briandeer.com