Sunday, May 12, 2013

Andrew Wakefield and Crohns Disease


Andrew Wakefield and IBD


Andrew Wakefield, a former physician at the center of the anti-vaccination controversy, had a fairly prolific publishing and research history before his fall from grace.  While Wakefield’s infamous vaccination paper made the headlines, many don’t realize that his previous work was as a researcher into Crohn’s disease.  What happened in the controversy, and how should we now view Wakefield’s work on Crohn’s disease?

Wakefield is a former physician came to infamy with his paper that linked autism and vaccinations in 1998.  Published in the Lancet (and now retracted), the paper looked at a small number of autistic children and claimed to link their autism to recent vaccinations with the measles, mumps, and rubella (MMR) vaccine.  According to Wakefield’s paper, 12 children developed autism shortly after being vaccination, with the MMR vaccine noted as a proximal cause of the autism.  The paper stated that the children had previously never exhibited symptoms of an autism spectrum disorder diagnosis, and the immediate proximity to the vaccine led to the conclusion that there was a causal relationship.(1)

The studies presented by Wakefield were alarming, and elevated him to the status of a legend within the anti-vaccination community.  His work was cited as evidence that the mercury contained in vaccines (through the preservative Thimerosal) was the reason behind the increase in autism in the recent past.  Wakefield’s celebrity was short-lived, however, when other doctors in larger, better controlled studies failed to replicate his results.(2)

Wakefield’s work could have been a simple preliminary study with non-representative results, which are fairly common in medicine, but the increased publicity led to an investigation of the paper itself.  Wakefield’s co-authors voluntarily withdrew their names from the study, and Wakefield was left to defend it.   Led primarily by Brian Deer, funded by the Sunday Times of London, and published in the British Medical Journal, Wakefield’s work was found to be not only wrong but fraudulent.(3,4)  A few key points from the findings include:

·         Wakefield engaged the 12 subjects in preparation for a lawsuit he was involved in. (5)
·         Multiple children enrolled in the study had pre-existing cases of autism, before taking the MMR vaccine.
·         The funding for the individuals enrolled in the study came from the planned litigation.
·         All 12 of the cited cases were misrepresented on multiple factors, from the time of diagnosis to the diagnosis itself (not all of the subjects were even diagnosed properly).(3)

Following Deer’s work, the Lancet retracted the article, but not until 12 years of damage had been done by its alleged findings.  In 2010, the UK’s General Medical Council revoked Wakefield’s right to practice medicine in that country, citing his fraudulent behavior, and finding, as summarized by the Guardian:

[T]he GMC said he had failed in the care of vulnerable children and was guilty of "irresponsible and misleading reporting of research findings potentially having such major implications for public health".(6)

The decline in MMR vaccination rates has led to a resurgence in cases of the three diseases, and the impact in human suffering due to Wakefield’s actions make take decades to sort out. While this alone would be an interesting cautionary tale about non-evidence based medicine, there is a big link to IBD in this tale – Wakefield published numerous papers on Crohn’s disease, and believed the link between autism and MMR involved an IBD-like intestinal disorder called autistic enterocolitis.  While Wakefield’s MMR work has been thoroughly discredited, how do we treat his earlier Crohn’s publications?

Wakefield’s earlier work on the histopathology of Crohn’s included a highly cited paper “Pathogenesis of Crohn's disease: multifocal gastrointestinal infarction”, which characterized intestinal regions with active disease.(7)  Wakefield did work with both Ulcerative Colitis and Crohn’s segments in other forums as well, including well respected publications like Gut.(8)  Wakefield’s work rapidly moved into the territory of linking Crohn’s with the measles virus, and this became a focal point for his work until the controversial Lancet article.(9)  Because the articles all had multiple authors, it is difficult to dismiss all of their contents directly.  That said, other articles have since been retracted, including one from the American Journal of Gastroenterology that included the same patients as above.(10)

Despite his unethical behavior, Wakefield’s early work (before linking to the measles virus) appears to have been based on stronger evidence.  That said, there have been numerous follow-on works since that point which have further elaborated or replicated pieces of the results he put together.  As such, it is not necessary to cite any of Wakefied’s work directly.  To sidestep risk, any of the key points that have since been validated in other studies can be cited standalone.

Wakefield’s story show the value of evidence based medicine in taking to task behaviors that were found to be fraudulent.  While he committed fraud in that event, and we certainly need to revalidate his earlier works, the opposite of the appeal to authority consideration needs to be part of the skeptical evaluation.  Individuals like Linus Pauling went from brilliant scientist to evangelical and misguided outside his field of expertise.  While Wakefield is no Linus Pauling (and Pauling never committed fraud), the principle still applies – his earlier work should be judged on its repeatability in controlled studies, not on the integrity of the original source – that’s one of the beauties of science.

Bottom Line

·         Wakefield was an IBD researcher that turned to the dark side and committed fraud to promote an anti-vaccine agenda.
·         The current research has repeatedly shown no link between vaccines and autism.
·         Wakefield did some important work prior to his fraud, and that work has been repeated and validated.  The later studies are better citations due to the issues surrounding the later Lancet work.

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1.       Wakefield, Andrew J., Simon H. Murch, Andrew Anthony, John Linnell, D. M. Casson, Mohsin Malik, Mark Berelowitz et al. "Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children." Lancet 351, no. 9103 (1998): 637-641.
2.       Taylor, Brent, Elizabeth Miller, Raghu Lingam, Nick Andrews, Andrea Simmons, and Julia Stowe. "Measles, mumps, and rubella vaccination and bowel problems or developmental regression in children with autism: population study." Bmj 324, no. 7334 (2002): 393-396.
3.       Deer, Brian. "How the case against the MMR vaccine was fixed." BMJ 342 (2011).
4.       Godlee, Fiona, Jane Smith, and Harvey Marcovitch. "Wakefield’s article linking MMR vaccine and autism was fraudulent." BMJ 342 (2011).
5.       MMR and MR Vaccine Litigation Sayers and others v Smithkline Beecham plc and others - [2007] All ER (D) 30 (Jun).
7.       Wakefield, A. J., A. P. Dhillon, P. M. Rowles, A. M. Sawyerr, R. M. Pittilo, A. A. M. Lewis, and R. E. Pounder. "Pathogenesis of Crohn's disease: multifocal gastrointestinal infarction." The Lancet 334, no. 8671 (1989): 1057-1062.
8.       Sankey, E. A., A. P. Dhillon, A. Anthony, A. J. Wakefield, R. Sim, L. More, M. Hudson, A. M. Sawyerr, and R. E. Pounder. "Early mucosal changes in Crohn's disease." Gut 34, no. 3 (1993): 375-381.
9.       Wakefield, Andrew J., Anders Ekbom, Amar P. Dhillon, R. Michael Pittilo, and Roy E. Pounder. "Crohn's disease: pathogenesis and persistent measles virus infection." Gastroenterology 108, no. 3 (1995): 911-916.

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