NEW questions about the ethics of the controversial study that linked the MMR vaccine to autism in children will be raised in Parliament today, The Times has learnt.

Less than a week after the doctor who pioneered the research was accused of failing to disclose a £55,000 payment, ministers are to be asked whether he had received proper ethical approval. The fresh doubts centre on whether the lumbar punctures to which autistic children were subjected by Andrew Wakefield’s team at the Royal Free Hospital were clinically justified.

While The Lancet, the journal that first published the research, cleared the researchers of failing to secure the full backing of the hospital’s ethics committee, the Liberal Democrat MP Evan Harris will today question whether it was right to reach this verdict.

Dr Harris, a doctor and former health spokesman, said documents indicate that the design of Dr Wakefield’s study was altered after it was approved by the Royal Free’s ethics committee. The panel does not appear to have been asked to revise its decision in light of the changes, which affected which children could be given lumbar punctures — a procedure performed under sedation in which spinal fluid is removed with a needle.

Dr Harris has tabled a written question to John Reid, the Health Secretary, asking whether the Government considers that the study was performed within ethical guidelines.

“How has he satisfied himself that lumbar punctures carried out on children at the Royal Free Hospital by the inflammatory bowel disease study group since 1996 have had valid and effective ethical approval from a properly consituted ethical committee, on the basis of the researchers’ relevant interests and the full clinical context?” he asks.

The new criticisms of Dr Wakefield’s work follow The Lancet’s announcement last week that it would not have published the 1998 paper had it known that the lead authorhad been paid £55,000 as part of a legal action against the MMR vaccine’s manufacturers. An investigation for The Sunday Times by Brian Deer found that Dr Wakefield had failed to declare the payment, even though “four or five” of the twelve children in the study were also involved in the litigation. Richard Horton, the Editor of The Lancet, said non-disclosure left the original study “fatally flawed”.

Both the journal and the Royal Free rejected Mr Deer’s charge that the ethical background to the study was weak, but documents released yesterday on the journalist’s website have prompted Dr Harris to raise further questions.

His concerns surround the diagnosis of the condition of the children in the study, which appears to have changed after it was approved by the hospital’s ethics committee. The original protocol suggested that Dr Wakefield’s team intended to investigate children with disintegrative disorder, an extreme, late-onset form of autism known as DD. Lumbar punctures for such patients as they would normally be conducted anyway to rule out other potential causes.

When the team’s findings were published in The Lancet, however, only one of the 12 children studied had a possible diagnosis of DD. The others had a diagnosis of either autism, an autistic spectrum disorder or encephalitis from vaccine or viral damage. None of these conditions would normally require a lumbar puncture for medical reasons, Dr Harris said, yet the procedure was performed anyway. “Why, when the scientific rationale changed and it was a different study, do they not appear to have gone back to the ethics committee?” he said. He urged Mr Reid to call a public inquiry into the affair.

Independent neurologists said that it was appropriate for scientists to seek renewed ethical approval when a study’s terms were altered, and that the clinical justification for lumbar punctures was very different for patients with DD and autism.

“If they included patients who didn’t fulfil the original diagnostic criteria then they should have gone back,” Carlos de Sousa of Great Ormond Street Hospital, said.

A spokesman for Dr Wakefield said that he did not wish to comment. A spokeswoman for the Royal Free Hospital said his former colleagues were unwilling to add to statements released last week.

Last Friday, Professor Humphrey Hodgson, Vice-Dean of Royal Free and University College Medical School, said: “We are entirely satisfied that the investigations performed on the children reported in the Lancet paper had been subjected to appropriate and rigorous ethical scrutiny.” The Lancet found that the evidence did not support the allegation that proper ethical approval was not received. “The evidence we have seen indicates that ethics committee approval was given for data collection from clinically indicated investigations in the children with an initially undiagnosed illness and who were described in the 1998 Lancet paper,” it said.

A question of ethics

• Research programmes at hospitals are put before local ethics committee which decide if they are appropriate
• Committee members usually include hospital staff and lay people. They take into account the risks posed, the benefits to the patient and any broader benefits
• Doctors and scientists must apply for ethical review for any study involving NHS patients
• The committees were established in 1967. In 1991 the Department of Health said that no NHS body should support research not approved by an ethics committee

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