Brian Deer on Andrew Wakefield: Pathology reports solve “new bowel disease” riddle
Posted Nov 09 2011 7:43pm
Today the British Medical Journal (BMJ) released a four articles on Andrew Wakefield and his research efforts at the Royal Free Hospital. To sum up the four articles in a single sentence (from Fiona Godlee of the BMJ): “Previously unpublished histopathology grading sheets apparently completed by Amar Dhillon, the senior pathologist on the paper, remove any remaining credibility from the claim that the Royal Free doctors had discovered a new inflammatory bowel disease associated with MMR”
For those who may wish a bit of background, earlier this year, the BMJ had a series of articles on Mr. Wakefield’s research:
Mr. Wakefield’s work focused on gastrointestinal disease. He went so far as to claim to have found a new syndrome, which he coined autistic enterocolitis . 13 years later, there is still no proof such a condition actually exists. When evidence came forward that the discussion of the children in the Lancet did not match the clinical records, Mr. Wakefield claimed that ““Dr Dhillon’s diagnosis formed the basis for what was reported in the Lancet,” and “I played no part in the diagnostic process at all.” Unfortunately it has been difficult to verify these statements. For one, the slides made from the samples taken from the children in the Lancet study are apparently missing, so direct comparison of what was reported in the paper to what was actually found in the children was difficult. Also, Dr. Dhillon’s analyses were not available. Until now. The scoresheets used by Amar Dhillon , the pathologist coauthor on the 1998 Lancet article, were recently made available to the BMJ. These form the basis for the articles published today.
Mr. Deer shared the reports with a number of professionals for comment. Including Dr. Henry Appleman :
“Most of this stuff is so close to normal that you’ve really got to question whether there is really anything there,” said Henry Appelman, professor of surgical pathology at the University of Michigan and a specialist in gastrointestinal disease. “These are the kind of things that we in our practise here would ignore completely.”
“Everyone thinks I am crazy even asking them,” said King’s gastroenterologist Bjarnason, after discussing the scorings with other specialists. “All but one of the children is normal in their eyes. There is no enteritis and no colitis, simple as that.”
While the reports were not striking, there is indication of inflammation. Mr. Deer argues that a key point was left out of the Lancet article, the presence of constipation in many of the children, which would have put the inflammation signs into better perspective for the readers:
No less controversial, the authors omitted from the paper the children’s principal gastroenterological problem. “Almost all” had “severe” constipation.(30) The GMC panel heard, for example, that after bowel preparation by nasogastric tube, the first patient, who had mild caecal cryptitis, endured two attempted ileocolonoscopies that failed because of faeces in the caecum, with “scope trauma” noted on the second.
This omission of constipation was no small matter. It went to the heart of how the paper would be read. Specialists told me that both mild inflammation and prominent lymphoid follicles may be expected to be associated with this sign.
(30)Murch S, Thomson M, Walker-Smith JA. Authors’ reply. Lancet 1998;351:908.
Mr. Deer, of course, is not a medical professional. But, we do not have to rely solely on Mr. Deer’s report. The BMJ has two companion pieces by medical professionals.
In Commentary: I see no convincing evidence of “enterocolitis,” “colitis,” or a “unique disease process”, Karel Geboes , Professor Doctor, Department of Pathology Univ Hospital KUleuven reports:
In general, the data are rather similar to the reports of the Royal Free hospital pathology service, which I reviewed for the BMJ last year.(7) Although minor abnormalities are noted in a minority of patients, I see no convincing evidence of “enterocolitis,” “colitis,” or a “unique disease process” being present in all patients. The Wakefield et al paper is obviously problematic and its wording does not reflect the data shown in the grading sheets.
(7) Deer B. Wakefield’s “autistic enterocolitis” under the microscope. BMJ 2010;340:c1127.
In Commentary: We came to an overwhelming and uniform opinion that these reports do not show colitis, Dr. Ingvar Bjarnason , professor of digestive diseases, consultant physician and gastroenterologist at King’s College, London, writes:
The hospital pathology service found the histopathology to be normal,(3) and, except in the case of the child mentioned above, the grading sheets also note normal findings. The fact that these scores were interpreted as abnormal raises, in my opinion, questions for the authors of Wakefield et al to answer, and particularly for the consultant histopathologists.
From the histological and endoscopic reports, there are no grounds to believe that any new inflammatory bowel disease may have been discovered, or any possible “unique disease process” observed, as reported by Wakefield et al. Nothing can be said about the aetiology of any minor irritations noted, and nothing can be inferred regarding treatment.
(3) Deer B. Wakefield’s “autistic enterocolitis” under the microscope. BMJ 2010;340:c1127.
In Institutional research misconduct, Failings over the MMR scare may need parliamentary inquiry, BMJ editor Fiona Godlee discusses how there is no sign that the Royal Free Hospital (University College London) has begun the expected inquiry into the misconduct which occurred there in the 1990’s:
It is now more than 18 months since the UK’s General Medical Council found Andrew Wakefield guilty of dishonesty and other serious professional misconduct(1) ; and it is nearly a year since the BMJ concluded that his now retracted Lancet paper linking the measles, mumps, and rubella (MMR) vaccine with autism and bowel disease was an “elaborate fraud.”(2) (3) At that time, January 2011, we called on Wakefield’s former employer, University College London (UCL), to establish an inquiry into the scandal. Ten months on, no inquiry has been announced.
Ironically, these data were made available to the BMJ with the intent of exhonerating Mr. Wakefield.
In 1997, Dhillon was asked to reassess intestinal biopsy specimens taken from children enrolled in Wakefield’s research after the hospital’s histopathology service, under consultant and fellow coauthor Susan Davies, reported most of the children’s biopsies to be normal. His 62 A4 grading sheets were sent to the BMJ by c, a self employed environmental microbiologist. Lewis says he was given them by Wakefield after they met at a vaccine safety conference in January. In his accompanying letter, Lewis concludes that a non-expert pathologist such as Wakefield could have thought they showed that the children had non-specific colitis.
Ms. Godlee is being kind, in my opinion, using the title the self-styled “vaccine safety” conference chose. This was the same conference in Jamaica which was discussed here at Left Brain/Right Brain recently.
It strikes me as rather odd that Mr. Wakefield did not provide these documents to the BMJ directly. Perhaps in a response to the articles published earlier this year. What advantage he gained in providing them through a proxy is unclear.
When he was found guilty of misconduct by the GMC, Mr. Wakefield vowed that he would not go away. So far, this appears true. However, his arguments are getting weaker as time goes on. In this case, they seem to have outright backfired. Writes Ms. Godlee:
The grading sheets are certainly interesting, but not for the reasons Lewis (or, it may be assumed, Wakefield, in giving them to him) intended. We sent them to two independent reviewers and supplied the data for comment to two further senior gastroenterologists. We also showed them to Brian Deer, the investigative journalist who over the past eight years has uncovered the secrets behind the MMR scare and who arguably knows more about this case than anyone apart from Wakefield. Our expert reviewers are in no doubt that Dhillon’s findings—like Davies’s before him—are almost all normal, or as near to normal that the changes they reported were likely to be physiological.(6) (7) In an accompanying feature article, Deer explains what they add to our knowledge of the Wakefield saga.(8)
(6) Geboes K. Commentary: I see no convincing evidence of “enterocolitis,” “colitis,” or a “unique disease process.” BMJ 2011;343:d6985.
(7) Bjarnason I. Commentary: We came to an overwhelming and uniform opinion that these reports do not show colitis. BMJ 2011;343:d6979.
(8) Deer B. Pathology reports solve “new bowel disease” riddle. BMJ 2011;343:d6823.