Sunday, February 21, 2010

And So the Spin Begins

Age of Autism has finally broken it's silence regarding the departure of Andrew Wakefield from Thoughtful House. Since Mark Blaxill and Carol Stott, the latter also quietly removed from Thoughtful House's research staff, couldn't procure the services of PR powerhouse Max Clifford, he had to settle for the bumbling, albeit puppy-dog loyal, Dan Olmstead. Here is Wakefield's 'exclusive' statement to AoA:
“There has been an extraordinary outpouring of support from the autism community in response to the events of the last two weeks”, Wakefield told Age of Autism in an exclusive interview. “The most exciting part of it has been the opening up of an entirely new sort of opportunity that will allow me to continue my work on behalf of autism families.” Wakefield said he would provide more specifics on the nature of that opportunity soon. “In addition, I will now speak publicly to refute the findings that have been made against me. I know my necessary silence on these issues has troubled many parents in both the U.K. and the U.S. But I’m ready now to get back on the front foot and publicly contest the false accusations that have been made against me, my colleagues, and indirectly The Lancet children. It’s been long overdue.”

I can only take that to mean that Wakefield will adopt the nom de plume of 'Dr. Andy' as notable celebretricians and all chiropractors do. And "The most exciting part of it has been the opening up of an entirely new sort of opportunity that will allow me to continue my work on behalf of autism families.” sounds like a segue to the announcement of, 'Dr. Andy is available for children's birthday parties; his specialities are magic tricks, balloon animals and venipuncture.'

Dan, you're a little late to the party as the news of Dr. Wakefield's departure from Thoughtful House was announced 18, February. You also forgot to mention the departure of Arthur Krigsman from Thoughtful House as well. I'm sure the spin which has been fed to you by Wakefield and, in turn passed on, serves as temporary morale boost for your readers. But make no mistake, Thoughtful House is cleaning house and Wakefield, Krigsman and Stott are liabilities. If they can't support them, notably Wakefield in light of the recent UK General Medical Council Ruling, the Lancet retraction of his 1998 paper and the subsequent withdrawn monkey study from Neurotoxicology, it certainly makes me wonder who could.

Wakefield is finished. There has been no conspiracy; his original publication was based upon atrocious ethics and conflicts of interest, highly-flawed science and fudged medical records. It doesn't get much worse than that. This man is no hero; he's nothing more than a predator.

Thursday, February 18, 2010

Andrew Wakefield resigns from Thoughtful House!

Rumours had been going around since the early morning that Andrew Wakefield had resigned from his post as Director of Research at Thoughtful House. I have just had confirmation by email that he has indeed resigned. Note that this link now leads to their home page and the statement of support recently posted after the GMC ruling has disappeared from their landing page. They issued the following statement today:

The needs of the children we serve must always come first. All of us at Thoughtful House are grateful to Dr. Wakefield for the valuable work he has done here. We fully support his decision to leave Thoughtful House in order to make sure that the controversy surrounding the recent findings of the General Medical Council does not interfere with the important work that our dedicated team of clinicians and researchers is doing on behalf of children with autism and their families. All of us at Thoughtful House continue to fight every day for the recovery of children with developmental disorders. We will continue to do our very best to accomplish our mission by combining the most up-to-date treatments and important clinical research that will help to shape the understanding of these conditions which are affecting an ever-increasing number of children worldwide.

Call me Cassandra - I had indeed foreseen that this would happen on this blog.

Further commentary on Respectful Insolence here and here, and on LeftBrainRightBrain - this was Strike 4 (after the GMC ruling, the retraction by The Lancet, and the retraction of the NeuroToxicology paper). Can I predict there is more to come (this may cause some fallout for Wakefield for example)?

Friday, February 12, 2010

Monkey Business Indeed

The infamous monkey-hep B vaccine study, co-authored by none other than Andrew Wakefield, that was clearly part of a larger body of work has been withdrawn by the editors of Neurotoxicology after being accepted. First though, hat-tip to KWombles at Countering Age of Autism for the find. Last October, when the study was announced and e-published ahead of print, Just the Vax, Respectful Insolence and A Photon in the Darkness thoroughly debunked the methods and results but also highlighted the blatant conflicts of interest that remained undeclared in the study proof and corrected proof.

Elsevier's Policy on Article Withdrawl states:
An outcome of this principle is the importance of the scholarly archive as a permanent, historic record of the transactions of scholarship. Articles that have been published shall remain extant, exact and unaltered as far as is possible. However, very occasionally circumstances may arise where an article is published that must later be retracted or even removed. Such actions must not be undertaken lightly and can only occur under exceptional circumstances, such as:

Article Withdrawal: Only used for Articles in Press which represent early versions of articles and sometimes contain errors, or may have been accidentally submitted twice. Occasionally, but less frequently, the articles may represent infringements of professional ethical codes, such as multiple submission, bogus claims of authorship, plagiarism, fraudulent use of data or the like.

Article Withdrawal
Articles in Press (articles that have been accepted for publication but which have not been formally published and will not yet have the complete volume/issue/page information) that include errors, or are discovered to be accidental duplicates of other published article(s), or are determined to violate our journal publishing ethics guidelines in the view of the editors, may be “Withdrawn” from ScienceDirect. Withdrawn means that the article content (HTML and PDF) is removed and replaced with a HTML page and PDF simply stating that the article has been withdrawn according to the Elsevier Policy on Article in Press Withdrawal with a link to the current policy document.
At this juncture, it is purely speculation as to what led to the withdrawl of this study, however, it stands to reason that Andrew Wakefield's recent woes with the GMC rulings and the Lancet retraction of his 1998 study that implicated the MMR triple jab with his, entirely made-up, autistic enterocolitis diagnosis. In any event, it is safe to say that the withdrawl of this recent study by Neurotoxicology editors indicates something untoward.

There is no doubt that anti-vax sites like Age of Autism and Generation Rescue will use this opportunity to screed about 'persecution', 'suppression', 'censorship' and 'conspiracy' and keeping the 'Brave Maverick Doctors' down. But that is simply not the case. There is no doubt that that editors of reputable journals don't take such actions lightly and will have to answer for them. So whether this is a case of the science or ethics being more closely-scrutinised and/or the massive, undeclared conflicts of interest coming to light, that is more than enough to justify the withdrawl of this study.

In any event, we hope that the anti-vaxxers can at least get it straight that there were 20 monkeys used for this study. Twenty monkeys that were sacrificed (sorry Orac) to further a warped personal agenda and not to advance our scientific knowledge.

Monday, February 1, 2010

"Independent" the Wakefield way (really something for the fail blog)

One of the claims that keeps reappearing in the comments sections under articles covering the GMC ruling on Andrew Wakefield and colleagues is that

The key finding (chronic colitis found in ASD children) of Dr. Wakefield's early case report published in The Lancet in 1998 HAS been independently confirmed by medical researchers in five different countries.

That is a very significant claim. After all, independent confirmation of a recent finding, would make the validity of a finding more likely, and if 6 independent laboratories found the same gut changes in autistic children, then then likelihood that this was a) a fluke or b) made up by Andrew Wakefield would be drastically reduced.

Finally, one of those commenters has posted those ‘independent confirmations’ – so I thought it might be worth having a look at them.

Krigsman, A. (Assistant Professor of Pediatrics, New York University School of Medicine Director of Gastroenterology Services), et al.,Ileocolonoscopy in Children with Autistic spectrum Disorder and Chronic Gastrointestinal symptoms. Autism Insights 2010:2 1-11.

Gonzalez, L., et al., Endoscopic and Histological Characteristics of the Digestive Mucosa in Autistic Children with gastro-Intestinal Symptoms. Arch Venez Pueric Pediatr, 2005;69:19-25.

Balzola, F., et al., Panenteric IBD-like disease in a patient with regressive autism shown for the first time by wireless capsule enteroscopy: Another piece in the jig-saw of the gut-brain syndrome? American Journal of Gastroenterology, 2005. 100(4): p. 979-981.

Balzola, F., et al., Autistic enterocolitis: Confirmation of a new infammatory bowel disease in an Italian cohort of patients. Gastroenterology 2005;128(Suppl. 2);A-303.

Galiatsatos, P., et al., Autistic enterocolitis: Fact or fiction. Canadian Journal of Gastroenterology. 2009;23:95-98.

Let’s look at number 1, Krigsman et al. The name sounds vaguely familiar. In fact, anyone who has read a little about the MMR-autism affair will know Arthur Krigsman as the clinical director of Thoughtful House, which happens to be the same Texas Clinic out of which Andrew Wakefield practises. One editor of “Autism Insight”, the journal in which this “independent confirmation” was published, is Andrew Wakefield (another one the senior author of the study, Carol Stott). Gosh, I bet peer review was harsh for this one.

Gonzales et al, number 2, has been published in Arch Venez Pueric Pediatr” which stands for Archivos Venezolanos de Puericultura y PediatrĂ­a. It was a bit tricky to get my hands on the paper, especially since the citation was not quite right, but I did manage and was not surprised to find that indeed the authors cannot replicate Wakefield’s 1998 “findings” of a distinct autistic enterocolitis, although they do report a higher incidence of gastrointestinal problems in their autistic group.

Balzola et al, number 3, is a case report of one adult autistic patient with inflammed bowel.

Similarly, Balzola et al, number 4, is a meeting abstract that never saw the light of day as a peer reviewed study.

Autistic enterocolitis: confirmation of a new inflammatory bowel disease in an Italian cohort of patients.
Federico Balzola, Clauser Daniela*, Alessandro Repici, Valeria Barbon, Anna Sapino***, Cristiana Barbera**, Pier Luigi Calvo**, Marina Gandione*, Roberto Rigardetto*, Mario Rizzetto.

Dept of Gastroenterology. University of Turin. Molinette Hospital Turin, Italy

*Dept of Neuropsychiatry for Children. University of Turin Regina Margherita Pediatric Hospital, Turin, Italy ** Dept of Pediatric Gastroenterology. University of Turin Regina Margherita Pediatric Hospital, Turin, Italy *** Dept of Biomedical Science and Human Oncology University of Turin

Although the causes of autism are largely unknown, this long-life developmental disorder is now recognised to affect as many as 1 to 500 children. An upper and lower intestinal disease has been recently described in these patients (pts) in spite of gastrointestinal symptoms have been reported by the parents back more many years. This disorder comprising ileo-colonic lymphoid nodular hyperplasia (LNH) and chronic inflammatory colonic disease was called autistic enterocolitis: an association between autism and bowel disease was then proposed.

Nine consecutive male pts (mean age 18 years, range 7-30 years) with a diagnosis of autism according to ICD-10 criteria that showed chronic intestinal symptoms (abdominal pain, bloating, constipation and/or diarrhoea) were enrolled. After routinely blood and stool tests, gastroscopy and colonoscopy with multiple biopsies were performed under sedation. A wireless enteroscopy capsule was also performed in 3 adult pts.

Anemia and fecal blood positive test were found in 2 pts and 3 pts, respectively. Gastroscopy revealed mucosal gastritis in 4 pts, esophagitis in 1 and duodenitis in 1 pts. Histological findings showed a chronic inflammation of the stomach and duodenum in 6 pts (66%) but inconsistent with celiac disease. Macroscopic mucosal abnormalities (aphtoid ulcerations and loss of vascular pattern) were found in 1 pts (11%) at colonoscopy and a LNH in the terminal ileum in 4 pts. (44%) Microscopic colitis with intraepithelial lymphocytes and eosinophils infiltrations, mucosal atrophy and follicular hyperplasia was histologically present in all the pts (100%) whereas a chronic inflammation with iperemia and villous shortening of the terminal ileum was shown in 6 (66%) pts. The wireless capsule revealed areas of bleeding or patchy erythema, mucosal erosions and ulcers in both jejunum and ileum in 1 patients whereas a particular chronic jejunum and ileal erosive pattern was evident in the other two.

These preliminary data are strongly consistent with previous descriptions of autistic enterocolitis and supported a not-coincidental occurrence. Moreover, they showed for the first time a small intestinal involvement, suggesting a panenteric localisation of this new IBD. The treatment to gain clinical remission has still to be tried and it will be extremely important to ameliorate the quality of life of such pts who are likely to be overlooked because of their long-life problems in the communication of symptoms.

These findings do not support a distinct pathology unique to autism. Additionally, Wakefield's original claim was essentially, 'MMR vaccination, then appearance of gastrointestinal symptoms, then regression into autism'. So not only was Wakefield's original claim roundly disproven, but Balzola et al.'s findings do not indicate anything remotely descriptive of Wakefield's original claim. This abstract also remains just that, i.e. an abstract presented at a meeting 5 years ago and has not gone through any peer-review, nor publication.

Finally, number 5, Galiatsatos et al., is a case report, featuring two adult patients with gastrointestinal problems and an ASD diagnosis. The authors call for “more investigations” in their discussion.

So what do we have here? Three (3) genuinely published cases of autistic adults who had consulted a doctor for gastrointestinal problems and were found to have gastrointestinal problems. One conference report from April 2005 that has not gone through peer review and has not appeared in a real journal in the 5 years since the conference. One real study looking at over 50 autistic children which does not confirm Wakefield’s findings. And finally, one study by Wakefield’s buddies in a freshly founded journal run by Andrew Wakefield and his buddies, to say that their buddy Andy was really right all along – how is that for "independent" confirmation?!

Edited on 19 January 2011 to add a find that Sullivan from LBRB led me to - it appears that the 2007 and 2008 tax forms (990) from Thoughtful House mention a "VENEZUELA COLLABORATION" under the projects they fund - a bit of thoughtful googling produced this gem

Gastrointestinal Pathology in Autism Spectrum Disorders: The Venezuelan Experience by Lenny G. Gonzalez, MD

Meet Lenny Gonzales, another Wakefield "buddy".