THE EDITOR ASKS M.D. TO PEER REVIEW PRIVATE EYE’S MMR COVERAGE
M.D. writes: Private Eye got it wrong in its coverage of MMR. It gave undue prominence to unproven theories based on a small number of uncontrolled observations, and paid far less attention to the weight of evidence from large comparative studies that failed to find any association between MMR and autism. While the Eye cited potential conflicts of interest in many of the key supporters of MMR, it failed to point out any unethical or prejudicial behaviour by Andrew Wakefield.
The 1998 Lancet paper that started the scare has now been removed from the medical literature on ethical grounds; and Wakefield, its leading author, may soon be removed from the medical register. Clearly what precious research money there is should now be used to test more credible hypotheses for the causes of autism.
The Eye has never claimed that the link between MMR and autism or bowel disease was proven; rather that better research was needed to answer the question conclusively. And it stressed the danger of infectious disease and the importance of vaccination. M.D. twice asserted that he had no safety concerns about MMR and that both his children had been vaccinated (Eyes 1045 and 1096); but overall the Eye sided with parents who were suing the vaccine manufacturers, and its coverage was consequently one-sided.
The parents were supported not just by Wakefield but by 27 expert witnesses who submitted files to support their case, and an equal number behind the scenes. The 1998 Wakefield paper and press conference caught the medical community on the hop, and there was little evidence to refute the proposed link because trials simply hadn’t been done. When the Eye joined the controversy in 2001, there were plenty of specialists willing to support the possibility that Wakefield might be right.
So when should the Eye have bailed out?
Small trials and observations can eventually lead to proof, but only if their findings can be replicated in larger trials. The best attempt to replicate Wakefield’s original observations and hypothesis – that the measles component of the MMR vaccine can lead to inflammation in the bowel and cause the release of chemicals that promote autistic disorders – was headed by Ian Lipkin MD, of the Mailman School of Public Health of Columbia University, published in 20081. This was a case-control study looking at the timing of the onset of autism and gastrointestinal (GI) disorders, in relation to the MMR vaccine.
The study also looked for the presence of measles in the bowel tissue of 25 children with both autism and severe gut disorders and matched them for age with 13 children with similar gut symptoms but not autism. The median age of the autistic children and the control group was 5.5 and 5.1 years, respectively, and they got the first dose of MMR vaccine at about the same age – 15.3 versus 16 months.
The children were selected because their gut symptoms were sufficiently grave that a biopsy was indicated for clinical reasons, which allowed the researchers to obtain tissue samples for the current study and try to replicate the Wakefield research, which found measles virus RNA in bowel tissue of 77 percent of children who had both autism and gut disorders, but not in children in a non-autistic control group.
However, the Lipkin research found no difference between the two groups, with evidence of measles viral RNA found in only one case and one control, despite using three labs and the best molecular detection methods available. Neither did the timing support a link between the vaccine and either autism or gut disorders. Only 13 of the 25 children with autism had the vaccine before the onset of autism, and in only 16 had the gut symptoms preceded the autism.
Such invasive research on children is extremely difficult to recruit volunteers for, and get ethical approval for. Given the GMC’s condemnation of Wakefield for taking unethical shortcuts, it may now be much harder to perform similar or larger studies to add to the evidence base.
However, by far the strongest evidence that has failed to find a link between MMR and autism is epidemiological. Because autism is common, any association between it and the MMR vaccine would show up clearly in large population studies compared to a control group that had not had the vaccine.
In 2002, a large retrospective cohort study of 450,000 children who’d had MMR, and 100,000 who hadn’t, found no difference in rates of autism2. So if a link did exist between MMR and autism, it was so weak as to be statistically undetectable.
The trial was not perfect (a Cochrane review – the most rigorous and independent analysis of medical trials in existence – adjudged it to be of moderate risk of bias and the follow-up of children should have been longer3); but it had far more statistical weight than any trials preceding it. All of Wakefield’s four papers were excluded from the Cochrane review as they lacked any scientific weight (one was a small case series, two had no comparative data and one had no data at all).
Another large trial published in the Lancet in 2004 also found no evidence of a difference in the rates of autism in the two groups4 and the Eye reported the Cochrane findings in 2002 and 2005 that, when all the best available trials were analysed together, there was no credible evidence of a link between MMR and autism (Eye 1066 and 1145).
The Eye was right to keep asking questions on behalf of parents. There have been plenty of medical scandals exposed by investigative journalism, and plenty more to expose. This could have been one, but it wasn’t. By the time of the second Cochrane review, the Eye should have conceded the argument.
1 Hornig M, et al “Lack of Association between Measles Virus Vaccine and Autism with Enteropathy: A Case-Control Study” PLoS ONE 2008; 3(9): e3140. DOI: 10.1371/journal.pone.0003140
2 Madsen KM, Hviid A, Vestergaard M, Schendel D, Wohlfahrt J, Thorsen P et al. A population-based study of measles, mumps, and rubella vaccination and autism. N Eng J Med (2002); 347 (19): 1477–82
3 www.mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD004407/pdf_fs.html
4 Smeeth L, Cook C, Fombonne E, Heavey L, Rodrigues LC, Smith PG et al. MMR vaccination and pervasive developmental disorders: a case-control study. Lancet (2004); 364 (9438): 963–9