Motion made, and Question proposed, That this House do now adjourn.—[Mr. Ainger.]

10:02 pm
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Dr Evan Harris (Oxford West and Abingdon, Liberal Democrat)

I wish to discuss issues around clinical ethics and research ethics in the work done at the Royal Free hospital by the inflammatory bowel disease group since 1995. Before I start, I would like to declare my interests. I was a member of an all-party group that recently visited the American society of clinical oncology conference for four days in Chicago, which was organised and funded by the pharmaceutical company Aventis. I am a member of the British Medical Association medical ethics committee, although I am not speaking for that body. I also spent a number of years as a member of the central Oxford research ethics committee, which gave me direct experience of many of the issues that I will deal with tonight. I am a member of the all-party group on autism, and my father is a recently retired professor of paediatrics.

Autism is a serious condition, and all of us in the House need to be aware of how distressing it is to parents and other family members and how challenging and troubling autistic spectrum disorders are to the children and their families. The controversy surrounding the work of the inflammatory bowel disease group at the Royal Free should not detract from the need to improve the health and social care provided to the children or the need for more research into causation, diagnosis and treatment of developmental delay or regression in children. None of the criticisms that I make of the researchers, the ethical regulators and the Legal Services Commission should be taken to extend to the parents who gave their consent and co-operation to those studies in good faith. As we know, many of them still support the individuals involved and perhaps see no problem in what they did.

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. Documents revealed by the investigative journalist Brian Deer and by The Sunday Times raise major doubts about a far more serious matter than publication misconduct. By that, I mean doubts and allegations about whether children were exposed to unacceptable risks and unnecessary procedures.

I do not make those allegations lightly, conscious as I am of the need to avoid the abuse of parliamentary privilege, but 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. The papers to which I refer are published on Brian Deer's website: www.briandeer.com

In 1996, and subsequently, researchers in the inflammatory bowel disease study group subjected children to a battery of invasive tests. Those included upper GI endoscopy, which is passing a flexible telescope down the throat into the stomach and upper gut through the mouth or nose; ileo-colonoscopy, which is passing a flexible telescope through the anus and rectum right round the large intestine and into the small bowel; and spinal taps, which is passing a needle into lower back to drain some of the fluid that bathes the brain and spinal cord. Those procedures are not trivial on consenting adults, let alone on autistic children, who must be heavily sedated or even anaesthetised. In addition to those tests, the children underwent blood tests, brain scans and monitoring of electric currents in the brain.

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Dr Evan Harris (Oxford West and Abingdon, Liberal Democrat)

I shall certainly give way to the constituency MP for the Royal Free hospital.

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Ms Glenda Jackson (Hampstead and Highgate, Labour)

I am delighted that the hon. Gentleman remembers that the hospital is in my constituency. Is he disputing the fact that the hospital's ethics committee was concerned, particularly about the fact that the project required children to undergo, as he has just pointed out, an intensive regime of investigation? The hospital's ethics committee put that point to the senior clinical investigator, Professor John Walker-Smith, who replied:

"I can confirm that the children would have these investigations even if there were no trial."

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Dr Evan Harris (Oxford West and Abingdon, Liberal Democrat)

That is the key question, which I shall deal with. If that were the case, there would be less of a problem, although there would not be no problem at all. I do not believe that that was right then or that it is now.

In 1996, just as now, there were tough rules to protect children from being exposed to risk for research purposes. We are not judging this case by the standards of today but by the standards of 1996, when four separate sets of guidelines applied. The guidelines were published and circulated by the Department of Health in 1991, the British Paediatric Association—now the Royal College of Paediatrics and Child Health—in 1992, the General Medical Council in 1994 and the Royal College of Physicians in 1996. The guidelines made it clear that children should not be exposed to anything more invasive or risky than a blood test unless certain conditions—likely specific clinical benefit to the child—were met; that proper approval be sought in advance from a research ethics committee; that the advice and instructions of the research ethics committee be followed to the letter; that changes to the agreed arrangements be agreed in advance by the research ethics committee; and that patients or their parents be given all the necessary information about risks for them to able to give adequate and adequately informed consent.

The research ethics committee was bound by the same guidelines to refuse permission for any tests or procedures that were more than minimal risk if they were not in the best interests of the individual child. That means that so-called non-therapeutic research—as it was called at that time—where there was no likely clinical benefit to the child in terms of therapy, was not allowed to involve anything worse than a blood test.

I shall quote some of the guidance that existed around that time. The BPA guidelines 1992 state:

"Children are unique as a research group for many reasons. They are the only people, in British law, on whose behalf other individuals may consent to medical procedures. Many children are vulnerable, easily bewildered and frightened, and unable to express their needs or defend their interests . . . The physical integrity of children, as of all other people, is protected by law. Unless they, or their parents or guardians acting on their behalf, agree to it, nothing can be done lawfully that involves touching them . . . Parental consent will probably not be valid if it is given against the child's interests. This means that parents can consent to research procedures which are intended directly to benefit the child, but that research that does not come into this category can only be validly consented to if the risks are sufficiently small to mean that the research can be reasonably said not to go against the child's interests."

The Department of Health guidelines 1991 are similarly clear:

"Where the proposal is for non-therapeutic research, all of the above applies"—

criteria for other patients—

"but in addition the child must be subject to no more than minimal risk as a result of his/her participation."

The local research ethics committee

"should note that those acting for the child can only legally give their consent provided that the intervention is for the benefit of the child."

The BPA was very clear about what sort of procedures were considered minimal risk, low risk and high risk:

"High risk procedures . . . should be carried out only when research is combined with diagnosis or treatment intended to benefit the child concerned. It would be unethical to submit child subjects to more than minimal risk when the procedure offers no benefit to them, or only a slight or very uncertain one."

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Ms Glenda Jackson (Hampstead and Highgate, Labour)

Is the hon. Gentleman disputing what Professor Humphrey Hodgson, the vice-dean and campus director at the Royal Free and University college medical school, said in a statement issued on behalf of the school and the Royal Free Hampstead NHS trust:

"The committee, after clarifying a number of issues . . . and having taken expert advice, approved the protocol submitted.

The clinical management and the investigation of these children was performed at the Free by a dedicated team of consultant paediatric gastroenterologists, in full consultation with and agreement of the parents of the affected children."

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Dr Evan Harris (Oxford West and Abingdon, Liberal Democrat)

I disagree with the Royal Free when it says that the protocol was subject to rigorous ethical analysis, and I shall say why I do not think that the necessary requirements were met.

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Dr Evan Harris (Oxford West and Abingdon, Liberal Democrat)

I wish to make some progress, if I may.

According to papers released to The Sunday Times by the strategic health authority, the research ethics committee did not appear to ask an independent outside expert—that is, someone who is independent and outside and expert—whether the battery of tests could be considered of therapeutic value to the children. 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. That in itself is a shocking admission of incompetence, so the Department of Health should investigate every ethics approval that the committee has ever given for research on children, to see whether anything else was allowed through—in effect, on the nod.

The published paper stated that the investigations had been granted clinical ethical approval by the ethical practices committee of the Royal Free, but the research ethics committee says, in a letter from the chairman to the dean, dated 24 July 1998:

"On 9th July you wrote to me for my comment on the letter of Professor David Hull. In his letter Professor Hull states: 'I see that the investigations were approved by the Ethical Practices Committee of the Royal Free Hospital NHS Trust.' This is, of course, incorrect. We did not approve the investigations."

However, the paper says clearly that the investigations were approved by the ethical practices committee of the Royal Free hospital. They cannot both be right. I suspect that both are wrong, in some ways, but one at least is wrong.

As it happens, the researchers had submitted their application in a form to which approval might have been given, even if the research ethics committee had looked at it properly. The researchers asked for permission to carry out the tests on 25 children with a condition known as disintegrative disorder, which is also known as disintegrative psychosis or Heller's disease. DD is a much worse form of developmental disorder than autism, and the researchers stressed in their application that it is separate from autism. They said, in paragraph 5, "Scientific background", that

"disintegrative disorder differs from autism in the loss of motor and self-help skills and usually, too, in the lack of more complex stereotype behavioral patterns".

The researchers were clear on that point, and it is still the accepted view today. DD is of later onset and involves significant loss of acquired skills. DD is rare and, in a few cases, can be caused by a metabolic disorder that can be detected by high lactate levels in the cerebrospinal fluid. It could be argued that doing spinal taps on such children would allow doctors to diagnose a metabolic disorder, or to rule it out. Since such diseases are not treatable, generally speaking, the benefit is limited, but at least a benefit can be argued. However, no major group of doctors in the UK argued at the time, or argues now, that spinal taps be performed on children with autism for any clinical benefit, and certainly not as an excuse to obtain cerebrospinal fluid for private research contracts.

Despite getting research ethics approval to perform the tests only on children with disintegrative disorder and despite the researchers stating that the tests were clinically necessary to benefit the children, the published research shows that not one of the 12 children had DD. One was diagnosed "Autism? DD?", but not one had DD. Most had autism. In another paper published later in 1998—an abstract in Gut—the authors admit to carrying out the tests on 30 children, only two of whom had DD. By 2000, some 60 children had been subjected to endoscopies, according to an article in The American Journal of Gastroenterology, of whom only two had DD. When the research ethics committee gave approval for the application it saw, it made it clear that any changes to the proposed tests or the group of children should be cleared with it in advance. That is standard, and it is written in the letter of approval. The research ethics committee received no such request to change the protocol, so up to 30 children were experimented on with no proper ethical approval and with no likelihood of individual clinical benefit.

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Ms Glenda Jackson (Hampstead and Highgate, Labour)

Is it not the case that, in the initial request, the criteria for investigation were that children

"should have disintegrative disorder; have symptoms and signs of intestinal dysfunction, and there was a parental request for investigation to be undertaken"?

Is it not also the case that disintegrative disorder is a syndrome that is part of the autistic spectrum?

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Dr Evan Harris (Oxford West and Abingdon, Liberal Democrat)

The selection criteria at paragraph 7 of the protocol application include "presence of disintegrative disorder"; the applicants state that the syndrome is separate, and it is established in their argument that it could be caused by something that would make a CSF test worth doing, but not by autism. Autism was not mentioned in the scientific background; had it been, I suspect that the procedure would rightly not have been permitted. When CSF tests on autistic children were required for Legal Services Commission purposes, no hospital in the UK gave ethics approval and children had to be taken to America for the tests. I hope that the hon. Lady understands the point that I making—[Interruption.] I want to continue.

It turns out that Dr. Wakefield was receiving undisclosed funding for at least four of the children from the Legal Aid Board for some of the results. A central component of the deal was genetic analysis of fluid collected from those spinal taps, with further undisclosed payments for genetic analysis of biopsy samples from the bowels, following endoscopy. The evidence strongly suggests that, from start to finish of his research, Dr. Wakefield withheld the information about his legal aid board funding interest from the REC.

The question in the protocol application under paragraph 10 was,

"How are the substances for the study being provided, and how is the study being funded?"

The reply was

"Clinical research at the Royal Free Hospital (ECR)".

There was no mention of any Legal Aid Board funding. The failure to disclose that information suggests that even the approval Dr. Wakefield received for 25 children with DD may be invalid. It also seems clear that he had no ethical approval to carry out those procedures on any child who did not have DD.

Without ethical approval, the consent that the doctors obtained from the parents may not be valid. Without a valid consent, doctors could face action for assault. I do not dispute that the parents gave consent in good faith, knowing that there was REC approval for the study—albeit apparently for a different study from the one that was carried out—but even valid parental consent does not make it lawful to conduct high-risk research procedures on children with no likely clinical benefit.

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Dr Evan Harris (Oxford West and Abingdon, Liberal Democrat)

I must conclude, so that the Minister has time to reply.

The whole affair seems dubious. It is not just that there was non-declaration of interest, nor that up to 30 children were exposed to invasive procedures under those tests, but that many more may have been thus exposed in tests agreed and funded by the Legal Services Commission with no ethical oversight at all.

The GMC—currently the Government's favoured path—cannot investigate or judge the LSC. It cannot look into the actions of non-medically qualified management. It cannot make recommendations to prevent any such practices from happening again, nor can it look for similar acts. That is why an independent inquiry is needed—not a hospital inquiry. The accused cannot investigate themselves, especially because, as the letter read out by Glenda Jackson shows, they have already declared themselves not guilty.

An independent inquiry is needed and the Government must order one. After all, such activities could still be going on at the Royal Free or elsewhere. Children need protection from that sort of research behaviour. If the Government cannot guarantee that it is no longer happening at the Royal Free or anywhere else, they have no choice but to order an independent inquiry.

10:18 pm
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Miss Melanie Johnson (Parliamentary Under-Secretary, Department of Health; Welwyn Hatfield, Labour)

I congratulate Dr. Harris on securing a debate on this important subject.

Like all Members, I care greatly about the health and safety of children and I am reassured that some of the infectious diseases that used to be devastating in childhood are now seen only rarely, if at all in some cases. It is easy to forget the impact that some of those diseases had. Nowadays, parents in the UK never see their children crippled by polio. Diphtheria and tetanus are exceptionally rare in children. Since the meningitis C vaccine was introduced in the UK in the 1990s, it has cut the rate of that terrible disease by 95 per cent.

Immunisation in the UK has been greatly successful at protecting children against preventable diseases, and all those achievements have happened because of effective vaccination programmes. In particular, measles cases fell from more than 70,000 a year in 1987—before MMR was introduced—to fewer than 100 per year in 1999. Before MMR, there were between 15 and 20 deaths each year, but no child has died of acute measles for a decade.

One of the greatest achievements was the prevention of congenital rubella syndrome and the avoidance of rubella-associated terminations of pregnancy. In 2001, there was not one single case of congenital rubella syndrome in England and Wales in which a woman acquired the infection in this country. Let us not forget mumps. Before MMR, it was the commonest cause of viral meningitis and lead to around 1,200 hospital admissions a year. The MMR vaccine has dealt a hammer blow to these three serious diseases of childhood and has released children from the risk of death and disability as a consequence, which is something with which I know that the hon. Gentleman and my hon. Friend Glenda Jackson agree.

The hon. Gentleman indicated that he is well aware of the significant media interest in MMR following the findings of an investigative journalist, Mr. Brian Deer, from The Sunday Times. Mr. Deer raised several concerns about the research carried out at the Royal Free hospital that first claimed a link between MMR and autism. The first concern was an alleged conflict of interest, and the editor of The Lancet has made it clear that the information now makes the original Lancet paper "fatally flawed". The second concern is about ethics approval for the research carried out at the Royal Free hospital, and I shall address that matter next.

As the hon. Gentleman emphasised, ethical approval, especially regarding children, is an essential part of medical research, and such medical research involving children is a matter of increasing concern. It can be an important means of promoting child health and well-being, but as the Royal College of Paediatrics and Child Health clearly recognises in its "Guidelines for the ethical conduct of medical research involving children",

"Children are unique as a research group for many reasons. They are the only people, in British law, on whose behalf other individuals may consent to medical procedures. Many children are vulnerable, easily bewildered and frightened, and unable to express their needs or defend their interests."

The importance of evaluating the possible benefit, harm and cost of research on human beings, and the possible ways of carrying out that research, are key issues. The benefits of research can be great, especially if the condition being investigated is common or if the research has a high chance of success. Possible harm must be assessed with equal care, and possible considerations of harm include questions of how invasive the type of intervention is, how severe the risks associated with the research procedures are, and how likely damage is to occur. These are common-sense issues that are difficult to question. Any parent would expect that research carried out on their children should have addressed those issues thoroughly and carefully, but balancing the pros and cons of research is often complex, as I know that the hon. Gentleman appreciates. Research ethics committees play a vital role in considering the issues and advising on what is acceptable and what is not.

Ethics committees are faced with the paradox of trying to be both stringent assessors and an approachable forum to help researchers to resolve problems. They have to compromise between aiming for the perfect protocol in advance and encouraging researchers to respond to families' unpredictable responses, which might require changes to research design later on.

Questions have been raised about whether the lumbar punctures and colonoscopies that were carried out on children at the Royal Free were justified. Both interventions are invasive and are not undertaken lightly. Lumbar puncture—during which cerebrospinal fluid is extracted from the spinal cord for examination—is undoubtedly unpleasant and is not risk-free. Colonoscopies are unpleasant and distressing to the patient, and carry the risk of complications, such as perforation of the bowel.

Should children at the Royal Free have undergone such investigations? Professor Sir David Hull and Professor Brent Taylor raised concerns in 1998. The research team believes that the investigations were justified, but I cannot say what was clinically justified for each of the children in the study. However, that shows why the approval of research proposals by ethics committees is so important.

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Ms Glenda Jackson (Hampstead and Highgate, Labour)

Is it not also the case that the independent ethical committee raised those very issues in 1996, before permission was given for the investigations to proceed?

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Miss Melanie Johnson (Parliamentary Under-Secretary, Department of Health; Welwyn Hatfield, Labour)

I am not an expert on all the details of the arrangements and I would not want to disagree with what my hon. Friend suggests, but we need to be certain that the right processes are being carried out. Ethics is about good practice. As the Royal College of Paediatrics and Child Health recommends, each research ethics committee that considers a project involving children should be advised by people with a close practical knowledge of babies and children. The ethics committee also needs to have, or to have access to, the appropriate expertise to cover the breadth of issues dealt with by the research proposal. That is demanding because of the complexity of much of the research undertaken. Input from independent experts is a means of ensuring that the committee can cover all the issues.

The hon. Gentleman made an important point about the management of research at the Royal Free. I am sure that the hospital and my hon. Friend, as the local MP, will take careful note of his points and that the hospital will consider his concerns in the light of the statements it has made.

The General Medical Council is considering serious matters of research and ethical conduct. We must await its deliberations and its indication of how it intends to take them forward in using its statutory powers. I assure the House that should aspects of the case require further scrutiny or investigation at that point, we will give them the most serious consideration and act appropriately. I assure the hon. Gentleman that we are waiting for the outcome of the GMC's deliberations and will give them careful consideration. I trust that the Royal Free will also look at what he said and think about the appropriate response.

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Dr Evan Harris (Oxford West and Abingdon, Liberal Democrat)

I am grateful to the Minister for her considered response. I raised my concerns with her some days ago. Does she accept that the GMC cannot consider the conduct of, and the procedures that were funded by, the Legal Services Commission because that is not part of the inquiry? Does she also accept that there may be other practices elsewhere of which she and the Department of Health may wish to take note? Are there not grounds for considering a wider inquiry, because there may be another form of investigation—by the Crown Prosecution Service—for which the GMC would want to wait?

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Miss Melanie Johnson (Parliamentary Under-Secretary, Department of Health; Welwyn Hatfield, Labour)

It is conceivable, although perhaps not likely—it is not for me to comment on the likelihood either way—that the case has not been brought to a final conclusion. The LSC has refused to grant further financial support for the litigants' case and it appears that it will not continue. However, notwithstanding the privileges that the House enjoys, it would not be appropriate for us to comment on something on which theoretically, if not practically, legal proceedings were still pending.

I take the hon. Gentleman's point about the ethics committees. I am sure that the Royal Free has listened carefully to what he said.

Question put and agreed to.

Adjourned accordingly at twenty-eight minutes past Ten o'clock.