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Histopathologist from the Lancet study Rebuffs Brian Deer’s Article in British Medical Journal

Histo By John Stone

A letter in on-line BMJ today from, Susan E Davies, one of the signatory histopathologists to the Lancet paper (HERE), rebuts Brian Deer’s imputation that there was anything amiss with the interpretation of the histopathology results in the study. This should finally knock on the head the claim made by Deer first in the Sunday Times in February 2009 that Andrew Wakefield had manipulated the results of the biopsy tests for his own purposes (HERE & HERE ).

Deer wrote in his article published a fortnight ago (HERE):

“The lead pathologist for the Wakefield project, and an author of the now retracted paper, was Susan Davies, now at Addenbrooke’s Hospital, Cambridge. At weekly meetings with paediatricians, the unexceptional results were confirmed. For four of the 12 she made additional notes recording the position more bluntly: "no abnormality detected". “

Deer based his report on evidence given by Davies to the GMC hearing in 2007 but it now looks clear that he put too much emphasis on isolated statements. Instead, Davies’s letter substantially corroborates the account of the matter that Wakefield gave in his complaint to the UK Press Complaints Commission (HERE). This is the text of Davies’s letter (HERE):-

Caution in assessing histopathological opinions. 30 April 2010

As one of the pathologists in question, I wish to respond to some of the issues raised in the recent article by Brian Deer(1), and accompanying editorial by Nick Wright(2), on the histopathological aspects of autistic enterocolitis. There is some misrepresentation of my involvement and lack of understanding of the process in studies involving histopathology.
Firstly, at the time in question I was working solely for the NHS and acted as the key pathologist for the clinical gastroenterology paediatric team. I was not the lead pathologist for this, or any other Wakefield project.



Secondly, I was not responsible for reporting the majority of the biopsy specimens from the twelve children, initially written up in the Lancet paper(3). This period predated the advent of subspecialty reporting and a number of consultants, each with varying levels of expertise and gastroenterology interest, were responsible for reporting these cases. It is erroneous to consider these reports to be more accurate than any subsequent review. Nick Wright writes that there is nothing intrinsically wrong with such a review of the histopathology. I would state more strongly that ANY study of histopathology has more credence, with reduced inter- and intra-observer variation, when a systematic review, using defined structured criteria over a short time-frame, is performed.

As to the severity of any pathology, there was a gradual awareness by those attending the regular clinicopathological conferences that we were identifying subtle changes in some of the mucosal biopsies from autistic children. Subtle does not always indicate insignificant: the focal features of cow’s milk protein enteropathy may be misinterpreted as normal; the hidden pathogen in immunodeficient syndromes is identified only by close scrutiny; the presence of Helicobacter pylori in gastric biopsies was previously not recorded, as they were considered insignificant.

The significance of any minor changes cannot be determined at the outset; the natural history evolves and/or may be altered by any therapy, but the changes must first be recognised. It may not be widely appreciated that the separation of the upper limit of normal from the lower spectrum of abnormal in histopathology is not always clear cut (and not only in the gastrointestinal tract).

Without going into extensive detailed histopathological description, there does appear to be some confusion within the discussion of these cases. It should be appreciated that the term ‘colitis’ covers a range of changes from minimal, self-limiting and non-specific, to extensive, severe and characteristic; as such it is difficult to select a point from within a spectrum for a single definition. Reference was made to focal active colitis(4), although later it is stated that minor changes are not to be called colitis. In personal practice, as evidenced at the GMC hearing, I had a different threshold from the other co-authors who performed the review and translated those findings into words.

While a clinical gastroenterologist might consider caecal active inflammation with incipient crypt abscess formation to be normal in children(1), this is a significant finding to be recorded by pathologists. The dismissal of ‘a bit of architectural distortion’ as insignificant underscores the problem of histopathological complexity as this, in fact, is a key feature in the assessment of colonic biopsies(5).

Time may indeed bring greater clarity to our understanding of what, if any histopathological changes may be associated with autism.

References
1. Deer B. Wakefield’s  ‘autistic colitis’ under the microscope. BMJ 2010; 340: 838-41.
2. Wright N. Does autistic enterocolitis exist? BMJ 2010; 340: 819-821.
3. Wakefield AJ, Murch SH, Anthony A, Linnell J, Casson DM, Malik M, et al. Ileal-lymphoid-nodular hyperplasia, nonspecific colitis, and pervasive developmental disorders in children. Lancet 1998; 351: 637-41.
4. Greenson JK, Stern RA, Carpenter SL, Barnett JL. The clinical significance of focal active colitis. Hum Pathol 1997;28:729-33.[
5. Jenkins D, Balsitis M, Gallivan S et al. Guidelines for the initial biopsy diagnosis of suspected chronic idiopathic inflammatory bowel disease. The British Society of Gastroenterology Initiative. J. Clin. Pathol. 1997; 50; 93–105.

Susan E Davies, 
Consultant Histopathologist
Addenbrookes’s Hospital, Cambridge CB2 0QQ 
Competing interests: None declared
 
John Stone is UK Editor for Age of Autism. 
 

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John,

It's crazy that the GMC and Brian Deer are just allowed to lie like this and go unchallenged in the media, and makes you wonder how this issue will ever get resolved.

Btw, did I say "article?" Sorry, I meant post. Dr. Davies wrote this, not you. Still awesome you found her letter, though.

Jake

Jake

I don't know about the article but it could not be a more significant event - Dr Davies is really sticking her neck out because she is not only saying that Deer misreported her and doesn't understand the data, she is also effectively saying that the GMC were incorrect in their findings on fact. The paper stated:

"All 12 children had intestinal abnormalities, ranging from lymphoid nodular hyperplasia to aphthoid ulceration. Histology showed patchy chronic inflammation in the colon in 11 children and reactive ileal lymphoid hyperplasia in seven, but no granulomas."

Meanwhile, the GMC panel - who had no expertise in this area - found that the invasive procedures were not justified on clinical grounds, and disregarded the totality of Dr Davies's evidence. Indeed, they have made their findings, not on the balance of probablilities, but beyond rerasonable doubt. But there is doubt, and its huge - also in the reliability of Deer's reporting.

In terms of the BMJ this is an unsavoury episode - not least because of the many parents who wrote in protesting - who were not posted. And how many other things may Deer have quoted out of context over the years? I know my views on that are well-known, but this poses it to the medical profession at large, and it will be difficult for Deer or BMJ to brush aside.

John

@Jenny Allen

The editor of the BMJ is very much in dissent suppression mode: the behaviour is frankly disgraceful.

Awesome article, John, and perfect timing, too. I just emailed "Selective Hearing: Brian Deer and the GMC" to my professor, TA and all the students in one of my classes. :)

I'm afraid the BMJ refused to publish my rapid response to Brian Deer's outrageous article. (I think the BMJ was even more outrageous for publishing this non medical rubbish!!) This is part of my comment:-

'In 1999, my grandson underwent a colonoscopy. Biopsies were taken and these demonstrated an increase in chronic inflammatory cells, which my daughter was informed, was due to microscopic colitis; terminal ileal lymphonodular hyperplasia, was also noted. (This is the ‘title’ given to this syndrome by Dr Wakefield in the original Lancet article; ‘non specific colitis’ is also mentioned in the article heading.) A member of Professor Walker Smith’s team stated this was ‘very much in keeping with our findings in other children with autistic spectrum disorder and bowel problems.’ It was also stated ‘This area remains very poorly understood’ and ‘the ‘cause remains unclear’, but ‘almost all of these children have a significant degree of constipation’ and that treatment for this was ‘usually clinically helpful’.

This is similar to what Dr Davies is trying to say in her response to Mr Deer's article. My daughter was told that the team at the Royal Free were still researching this.

John said,

"You sometimes wonder whether Ben lacks moral conviction."

I sometimes wonder whether Goldacre has any morals.

The editor of the BMJ has made a grave mistake in publishing Professor Sir Brian Deer's flawed histopathological treatise. British doctors deserve better. Or do they? Remember, it's the profession that has sponsored the farrago against the Royal Free Three.

'Science advances one funeral at a time.' - Max Planck

Carol

I am afraid that BMJ have a rather shoddy history of journalistic reporting and it also automatically gets listed on Pubmed. For instance, the central claim of a report by Meadow-Southall apologist Jonathan Gornall turned on his omission of the key word "only" from a document:

http://www.bmj.com/cgi/eletters/333/7579/1165#150643

But the article was never of course retracted.

The message is that absolutely anything goes if you are on a certain side, and nothing will be good enough or count if you are not.

In my comment below "dig in deeped" should of course have read "dig in deeper".

Odd that Deer didn't talk to Davies before characterizing her opinions for an important medical journal.

I would just like to re-post here my deleted comment from Ben Goldacre's Guardian blog this morning. Goldacre was reporting a possibly interesting piece of research about how people in entrenched positions only dig in deeped when shown compelling evidence against them.

http://www.guardian.co.uk/commentisfree/2010/may/01/bad-science-election-smears

Here is my comment:-

'1 May 2010, 8:41AM

'So, Ben, what do you do when the one of the histopathologists from Wakefield's Lancet paper comes out to dispute Brian Deer's account of her evidence to the GMC, or that there was anything fabricated about the results:

http://www.bmj.com/cgi/eletters/340/apr15_2/c1127#235073

'Does it just re-inforce your opinion of the guilt of Drs Wakefield, Walker-Smith and Murch, and that there was nothing wrong with the patients?

http://www.guardian.co.uk/science/2010/jan/28/mmr-vaccine-ben-goldacre

'Or do you agree with Dr Davies, consultant histopathologist at Addebrooke's hospital that Deer's claims should be viewed with "caution".

'Cue for lots of entrenched, angry remarks?'

You sometimes wonder whether Ben lacks moral conviction.

Good for her for speaking out!! And thanks, John for reporting this!

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