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Re: The MMR story is not complete
 

I should like to ask Richard Smith [1] how it could be that Ben Goldacre's account of the MMR story is complete when it has been made virtually impossible, particularly in this country, for those on one side of the debate to present their case, not least because proponents of MMR safety blank all criticisms? Meanwhile, and for long time the media - so far from supporting or giving space to Andrew Wakefield - have been largely intimidated into silence.

As it is Goldacre has never answered the challenge of the fundamental flaws in the epidemiology of MMR and autism, as, for instance, I set out for him in my Rapid Response of 21 September 2007 [2], citing four studies he had used in his pivotal award winning polemic 'Never Mind the Facts', published in the Guardian in December 2003 [3]. Three of the studies, I pointed out, were found when reviewed by Cochrane to be seriously deficient. In fact none of the six autism studies reviewed by Cochrane was judged to be of low risk of bias (and these were supposed to be the best). Cochrane demonstrated its own bias by suggesting that the absence of evidence for safety should be balanced against the need to eradicate the diseases, [4] [5] stating in conclusion:

"The design and reporting of safety outcomes in MMR vaccine studies, both pre- and post-marketing, are largely inadequate. The evidence of adverse events following immunisation with MMR cannot be separated from its role in preventing the target diseases." [4]

Moreover, it is less than certain that even if the epidemiology had been better conducted than it has been whether it would have necessarily given a clear answer regarding Wakefield's hypothesis. Almost unreported in this country the former head of the National Institutes of Health, Bernardine Healy, told CBS news earlier this year that the Institute of Medicine Review of 2003/4 had been over-dependent on epidemiology, and that in order to properly research the autism/vaccine issue you would have to look at medical subgroups (as, indeed, Wakefield had been doing)[6].

Also, almost unreported in this country has been the publication of the Hornig study [7], the first study to even half heartedly replicate the Uhlmann study of 2002, which layed out Wakefield and O'Leary's initial laboratory findings [8]. While the rhetoric surrounding the publication of the Hornig study has trumpeted in the US the final eclipse of the Wakefield hypothesis the interior detail suggests anything but (perhaps why we have heard so little of it so far in this country).

In the first place the study confirms the consistency of O'Leary's results with two most higly rated labs in the US. Secondly, while the study only had five cases which of the Wakefield pheno-type it confirmed two positive results for measles virus RNA from ileal samples, across all three laboratories - one from the autistic group and one from the control group, all of which had gut pathology (and all cases having MMR). The study does not tell us whether symptoms in two cases developed pre or post vaccination, though it would certainly bolster their case for "lack of association" if it was pre. And so far from disputing the results Uhlmann in the discussion it states:

"Our results differ with reports noting MV RNA in ileal biopsies of 75% of ASD vs. 6% of control children [10], [41]. Discrepancies are unlikely to represent differences in experimental technique because similar primer and probe sequences, cycling conditions and instruments were employed in this and earlier reports; furthermore, one of the three laboratories participating in this study performed the assays described in earlier reports. Other factors to consider include differences in patient age, sex, origin (Europe vs. North America), GI disease, recency of MMR vaccine administration at time of biopsy, and methods for confirming neuropsychiatric status in cases and controls. Participation in the current study required confirmation in cases of the presence of an AUT diagnosis and exclusion in controls of AUT or other developmental disturbances."

Another reason why we might find this troubling in this country is that study confirms the appropriateness of the kind of investigation for which Drs Wakefield, Walker-Smith and Murch are presently on trial at the General Medical Council. Not only is this a terrible injustice to the doctors - irrespective of whether the hypothesis is correct or not - but it has effectively infringed the rights of autistic children in this country who are now widely being denied appropriate medical support, as the National Autistic Society has warned [9].

[1] Richard Smith, 'Becoming Ben', BMJ 1 October 2008, http://www.bmj.com/cgi/content/full/337/oct01_3/a1856  

[2] John Stone 'Re: Restrictions on hospitality apply to doctors and journalists', BMJ Rapid Responses http://www.bmj.com/cgi/eletters/335/7618/480#176662  

[3] Ben Goldacre, 'Never mind the facts', Guardian 11 December 2003: http://www.guardian.co.uk/life/feature/story/0,,1103958,00.html  

[4] V Demicheli, T Jefferson, A Rivetti, D Price,[Review] 'Vaccines for measles, mumps and rubella in children', Cochrane (Wiley 2005), http://mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD004407/frame.html  

[5] Clifford G Miller, 'Questions on the Independence and Reliability of Cochrane Reviews, with a Focus on Measles-Mumps-Rubella Vaccine', http://www.jpands.org/vol11no4/millerc.pdf  

[6] CBS News,'Leading doctor: vaccines-autism worth study', http://www.cbsnews.com/stories/2008/05/12/cbsnews_investigates/main4086809.shtml  

[7] Mady Hornig, Thomas Briese, Timothy Buie, Margaret L. Bauman, Gregory Lauwers, Ulrike Siemetzki, Kimberly Hummel, Paul A. Rota, William J. Bellini, John J. O'Leary, Orla Sheils, Errol Alden, Larry Pickering, W. Ian Lipkin, 'Lack of Association between Measles Virus Vaccine and Autism with Enteropathy: A Case-Control Study', published 4 September 2008, http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0003140#s3  

[8] V Uhlmann, C M Martin, O Sheils, L Pilkington, I Silva, A Killalea, S B Murch, J Walker-Smith, M Thomson, A J Wakefield, and J J O'Leary, 'Potential viral pathogenic mechanism for new variant inflammatory bowel disease', Molecular Pathology, Mol Pathol. 2002 April; 55(2): 84–90, http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=11950955  

[9] NAS, 'General Medical Council hearing against Dr Wakefield', http://www.nas.org.uk/nas/jsp/polopoly.jsp?d=459&a=13952  

"The National Autistic Society (NAS) is keenly aware of the concerns of parents surrounding suggested links between autism and the MMR vaccine. The charity is concerned that the GMC hearing, and surrounding media coverage, will create further confusion and make it even more difficult for parents to access appropriate medical advice for their children.

"It is particularly important that this case is not allowed to increase the lack of sympathy that some parents of children with autism have encountered from health professionals, particularly on suspected gut and bowel problems. Parents have reported to the NAS that in some cases their concerns have been dismissed as hysteria following previous publicity around the MMR vaccine. It is crucial that health professionals listen to parents' concerns and respect their views as the experts on their individual children.

"There is an urgent need for further, authoritative research into the causes of autism, to improve our understanding of the condition, to respond to parents' concerns and to enable us to ensure that there are appropriate services and support in place to meet people's needs."