Autism and Vaccine cont...

•  Andrew Wakefield and his article in the Lancet
• Response to his article
• Thoughts from last discussion...scientific communication. Do we have any suggestions for improvement

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From The Times

May 25, 2010

Dr Andrew Wakefield struck off medical register

Raf Sanchez, David Rose

Andrew Wakefield, the doctor who triggered the MMR vaccine scare, has been struck off the medical register.

After nearly three years of formal investigation by the General Medical Council (GMC), Dr Wakefield has been found guilty of serious professional misconduct over “unethical” research that sparked unfounded fears that the vaccine was linked to bowel disease and autism.

Parents were advised yesterday that it was “never too late” to give their children the triple vaccine to protect against measles, mumps and rubella, as the case drew to a close.

The decision marks the culmination of the longest medical misconduct hearing in the GMC’s 150-year history, which has been going on since July 2007.

A fitness to practise panel has already found Dr Wakefield and two other doctors guilty of a series of charges over the way they conducted research on 12 children, published in The Lancet medical journal in 1998.

Announcing the final verdicts, Surendra Kumar, chair of the GMC’s fitness to practise panel, said that Dr Wakefield had been “irresponsible”, “misleading” and “dishonest”, in the way in which he carried out and presented the study, which involved carrying out unnecessary and invasive tests on children without official permission.

“The panel is profoundly concerned that Dr Wakefield repeatedly breached fundamental principles of research medicine,” Dr Kumar told the hearing in central London. “It concluded that his actions in this area alone were sufficient to amount to serious professional misconduct.”

Dr Wakefield, 53, also “showed a callous disregard” for the suffering of children by taking blood samples from them at his son’s birthday party, and failed to declare a conflict of interest — that he had received £50,000 to carry out research on behalf of parents who suspected that MMR could lead to autism.

Dr Wakefield’s former colleague, John Walker-Smith, 73, was also found guilty of serious professional misconduct and struck off the medical register for his role in carrying out procedures on the children.

Another doctor, Simon Murch, was not found not guilty, despite having previously been found to not have ethical approvals for the study.

The panel said that the decision to strike off Dr Wakefield was the “only sanction that is appropriate to protect patients and is in the wider public interest, including the maintanence of public trust and confidence in the [medical] profession.”

The doctors, formerly employed at the Royal Free Hospital in Hampstead, North London, sparked the biggest health scare in a generation when they published claims linking the vaccine, recommended to all infants at 13 months, to a new type of bowel disease, and also linked it to the development of autism.

The fallout from the study — including Prime Minister Tony Blair’s refusal to say whether his infant son had been vaccinated — caused hundreds of thousands of parents to boycott the jab. Immunisation rates fell, leading to a resurgence of potentially deadly measles cases in recent years.

The Lancet, which had withdrawn contested parts of the paper in 2004, subsequently retracted the article in full.

The GMC looked only at how the doctors’ acted during the research, not whether the findings were right or wrong — although they have been roundly rejected by medical experts and multiple large-scale studies.

Dr Kumar, who led a panel of three doctors and two lay members which sat and deliberated on the case for a total of 217 days, said that Dr Wakefield showed a continued lack of insight as to his misconduct.

Dr Wakefield, who moved to America in 2001, did not attend today’s hearing. He has previously said that the GMC’s case against him is “unjust and unfounded”.

He now has 28 days to appeal against the verdict at the High Court.

In a statement yesterday he said: “Efforts to discredit and silence me through the GMC process have provided a screen to shield the Government from exposure on the MMR vaccine scandal.”

But the Royal College of Paediatrics and Child Health said that the false suggestion of a link between autism and the MMR vaccine had done “untold damage to the UK vaccination programme”.

“We cannot stress too strongly that all children and young people should have the MMR vaccine. Overwhelming scientific evidence shows that it is safe,” it said.

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In this case, the actual paper contained no conclusive evidence, merely the suggestion that bowel leakage in children with gastrointestinal problems could cause the measles vaccine to spread into other parts of the body and affect the brain, possibly resulting in autism spectrum disorders. 

As a result of Wakefield's unscientific statements and the following media frenzy, vaccination levels dropped across Britain, and outbreaks of measles—and subsequent deaths—began occurring for the first time in decades. As other scientists began looking for a link between vaccines and autism, study after study foundthere was none. Yet the myth persisted in the popular mind, and people latched on to the belief that vaccines that protect against deadly diseases are not safe.

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 An interresting quote I found online: "It also undermines his claim that he is a good scientist by showing that he values anecdotal evidence (“listening to the parents”) over experimental evidence."

http://www.sciencebasedmedicine.org/?p=5343

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LONDON, ENGLAND, April 16, 2010 ---Today the British Medical Journal (BMJ) has published an online commentary authored by journalist Brian Deer in which he makes further allegations against Dr. Andrew Wakefield and the doctors involved in the 1998 Lancet study that first reported possible links between MMR and autism, without affording Dr. Wakefield an opportunity to respond simultaneously to these serious allegations online. Deer’s latest claims follow his February 2009 Sunday Times article accusing Dr. Wakefield of “fixing data” for which there is a pending complaint to the UK’s Press Complaints Commission (PCC). The BMJ’s press release regarding this latest published “special report” by Brian Deer, along with Dr. Wakefield’s point-by-point response, is below:

This week, the BMJ questions the existence of a new bowel condition in autistic children dubbed “autistic enterocolitis” by Dr Andrew Wakefield and colleagues in a now infamous and recently retracted paper published by the Lancet in 1998. 

In a special report, journalist Brian Deer tries to unravel the journey of the biopsy reports that formed the basis of the study, while an accompanying editorial asks does autistic enterocolitis exist at all?

In 1996, Dr Andrew Wakefield was hired by a solicitor to help launch a speculative lawsuit against drug companies that manufactured MMR vaccine to find what he called at the time “a new syndrome” of bowel and brain disease caused by vaccines.

FALSE. I was not hired by a solicitor to find a new syndrome of bowel and brain disease caused by vaccines. I acted as a medical expert in respect of two matters: first, to provide a report on safety studies of measles-containing vaccines; and second, to look for evidence of measles virus in intestinal tissues of children with Crohn’s disease, and children with regressive developmental disorder and intestinal symptoms who were undergoing investigation for possible bowel disease.

The proposed “new syndrome” was not what Deer claims. At the material time, the “new syndrome” consisted of gastrointestinal symptoms (not disease) in children with developmental regression. Prior to the clinical investigation of these children, the presence of intestinal disease had not been determined.

Deer reveals that biopsy reports from the Royal Free Hospital’s pathology service on 11 children included in the Lancet study showed that eight out of 11 were interpreted as being largely normal. But in the paper, 11 of the 12 children were said to have “non-specific colitis”: a clinically significant inflammation of the large bowel.

FALSE. The findings were correctly reported in The Lancet paper. The meticulous process by which the diagnoses were made in the children reported in that paper has been described on numerous occasions, including in published papers, in Mr. Deer’s presence at the GMC, in the complaint filed against him to the PCC that is published online1. For the avoidance of doubt, the clinical process involved two stages: routine reporting of the pathology by the duty pathologist, followed by a combined review by Professor Walker-Smith’s team and Dr. Sue Davies. During this clinical review, it was recognized that significant disease was being overlooked. It was decided to have all biopsies reviewed by the senior pathologist with greatest experience in bowel disease, Dr. Paul Dhillon. This research review was undertaken in a blinded, unbiased manner such that Dr. Dhillon was not aware of the diagnosis in any child. Dr. Dhillon’s diagnosis formed the basis for the findings reported in The Lancet. Dr. Dhillon’s review is referred to in The Lancet and is described in detail in subsequent papers that confirmed the presence of bowel disease in many more children with autism. Mr. Deer was aware of these facts when making his false allegations but does not appear to have disclosed this to the BMJ..

So how did the mismatches occur? 

Apparently, the biopsies were first reported on by Dr Susan Davies, a consultant histopathologist and co-author on the study, but they were also seen and interpreted by three other co-authors before final publication. When Dr Davies was cross examined before the General Medical Council she said that she had initially been concerned about the use of the term “colitis” in the Lancet paper because she herself had found nothing abnormal in the biopsy sections. But she was reassured, she said, by the “formalised review” of the biopsies by her three colleagues.

FALSE. This is not what Dr Davies said. Mr Deer fails to mention that Dr. Davies was referring, in her evidence, to her use of the term colitis only in terms of active colitis (involving an increase in pus-forming cells) rather than chronic colitis which was present in many children, In his selective misrepresentation of the evidence he also fails to mention that, later in her evidence, Dr Davies clarified how, as a distinct pattern of disease emerged in the autistic children (particularly following an unbiased review she undertook with Dr. Murch) this disease came to be termed ‘autistic enterocolitis’.

This apparent concurrence of four pathologists gave strength to the finding of a new bowel disease, writes Deer. But there is no suggestion in the paper that the second assessment caused findings to be substituted or changed. 

How many peer reviewers would have felt comfortable approving the paper if they had known that the hospital pathology service reported biopsy specimens as largely normal, but they were then subjected to an unplanned second look and reinterpreted, he asks?

FALSE. A planned “second look” was undertaken routinely by Professor Walker-Smith and his team at the weekly clinical meeting he held with Dr. Davies for this purpose. This planned review has Is been part of Professor Walker-Smith’s clinical practice, and is essential for quality control. It was at this point that discrepancies were found, and it was these discrepancies that led to a further planned review by Dr. Dhillon.

Professor David Candy, paediatric gastroenterologist at St Richard’s Hospital, Chichester, who reviewed the paper in 1997, said “no”: he wouldn’t have felt comfortable. “That’s an example of really naughty doing – to exclude the original pathology findings.” 

It is highly unlikely that Deer informed Dr. Candy of the extensive evidence refuting his false claims, or that on the basis of these false claims, Mr. Deer is the subject of a formal complaint to the PCC.

So what should we make of all this, asks Deer? The biopsy slides are no longer available, and cannot be re-assessed. All we have are Dr Davies' pathology reports, and independent specialists seem to agree that she regarded what they showed as largely unremarkable.

FALSE. Contemporaneous reports based upon Dr Dhillon’s formal assessments are available that confirm the findings described in The Lancet. 

Professor Tom MacDonald, dean of research at Barts and the London School of Medicine and co-author of Immunology and Diseases of the Gut said: “If I was the referee and the routine pathologists reported that 8/11 were within normal limits, or had trivial changes, but this was then revised by other people to 11/12 having non-specific colitis, then I would just tell the editor to reject the paper.” In an accompanying editorial, Sir Nicholas Wright also from Barts and the London points out that all histopathological interpretation is a matter of opinion, but we should always ask how reliable that opinion is.

CORRECT. It was precisely for this reason that the final diagnosis was left to the most senior pathologist with the most experience in bowel disease who assessed the tissues in an unbiased fashion.

In terms of whether autistic enterocolitis exists, several studies have shown an association between inflammatory pathology and autistic spectrum disorder, but he believes that, in view of the limited data, any firm conclusion would be inadvisable.

CORRECT. The finding of inflammatory disease of the intestine of autistic children has now been confirmed in 5 different countries.

Dr Wakefield said "It is extraordinary that a journal like the BMJ should have reduced itself to this sort of tabloid medicine from an entirely unqualified and biased source. The egregious errors in Deer's report should cause embarrassment to the BMJ's editors. In a relentless and misguided effort to distract attention from vaccine safety issues, agenda-driven journalism has once again made a mockery of medicine."

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Links: http://briandeer.com/solved/solved.htm

The Lancet Article: http://briandeer.com/mmr/lancet-paper.pdf

Class session summary (leah)

We began our discussion by questioning why this article was published in The Lancet, noting the small sample size of 12 participants. As a class, we were not sure what the editors at The Lancet were thinking.  Next, we talked about the grounds under which the article was retracted. Annie told us that the article was retracted due to falsification of data and financial incentive -the research was supported by parents who thought there was a link between vaccines and Autism.  As a class, we wondered if money from outside sources always creates conflicts of interest. We reached the conclusion that in some cases money can create conflicts of interest and affect how the results are reported. We realized that researchers should report any financial support during publication. Next, we discussed the effects of the press release for the paper and how it did more damage than the original publication. In the press release, Wakefield suggested splitting the MMR vaccine into three separate shots, despite the fact that his article did not discuss or support this claim. This led to a discussion of how people can take advantage of their positions as scientists and use their identity to gain credibility where there is none. We wondered if there should be a code of ethics for scientists that would require them drop their identity when they are not discussing their research/ area of expertise.  Or, alternately we thought there should be a campaign to educate the public that scientists are not authoritative sources of information. We also talked about how science articles can be picked up by the mass media and influence the public. We debated if journals like The Lancet were written for the public or for scientists exclusively. At the same time, we realized that news articles are not necessarily credible sources and  this can make the truth ambiguous. In the end of our discussion, Paul pointed out there are multiple issues related to Autism and vaccines, including the requirements for herd immunity and communication between science and the public.