http://www.thelancet.com/newlancet/reg/issues/vol354no9182/menu_nod12.html

     Sir--Hypothesis testing and presentation of the outcome--either positive or negative--is a fundamental part of the scientific process.

Accordingly we have published studies that both do (1) and do not (2) support a role for measles virus in chronic intestinal inflammation: this is called integrity. The latest of these studies was strongly positive (3) and was accepted by the MRC Review in February, 1998. By contrast, Brent Taylor and colleagues (June 12, p 2026) (4) have ignored the rules. They are inappropriately didactic in their conclusions, despite the weakness of their method and the contradictions in their data. A case-series analysis is unlikely to identify a relation between exposure and disease, in which the onset is insidious and in which, very often, there is diagnostic delay.

     Taylor et al tested the hypothesis that there should be no temporal clustering of first parenteral concerns with measles, mumps, and rubella (MMR) vaccination. They identified a statistically significant excess risk by 6 months after MMR, which they dismiss, post hoc, as indicating parential recall bias. Had this been the case it should have been seen in both of their vaccine groups--those receiving MMR and those receiving any measles-containing vaccine. The excess risk was seen only in the MMR group; this is a fundamental flaw. In 1998 the expected numbers of newly diagnosed autistic children in California should have been 105-263 cases, according to DSM-IV; the actual figure was 1685 new cases. The temporal trend in north-west London is almost identical, although the rise is delayed by about 10 years. The two countries use the same diagnostic criteria. The sequential trends are consistent with the timing of introduction of MMR to both regions. * Data from Departmental of Developmental Services, 1987-98 (www.dds.ca.gov).

     However, it pales into insignificance compared with their failure to declare the fact of an MMR catch-up campaign that was initiated in 1988 with the introduction of this vaccine. This campaign was targeted at children, whatever their age, who presumably had not received monovalent mumps or rubella vaccine whatever their exposure status. As such it was a novel and, in terms of safety, untested policy. On the basis of Taylor and colleagues' inclusion criteria, and taking account of the catch-up campaign, then those first birth cohorts who actually received MMR (circa 1986) were precisely those in whom a doubling of the numbers of cases of autism were seen.

Thereafter these numbers continue to increase strikingly. Omission of this essential fact--the catch-up campaign--requires explanation lest it be misconstrued.

     Can the dramatic increase in autism be ascribed to change in diagnostic practice? Data from the recent California report from the Office of Developmental Services belie this contention. The figure juxtaposes the data from California with those from north-west London. Identical temporal trends are shown, with the rise in autism from a steady baseline value, coinciding with the introduction of MMR vaccine as the single strategy in both countries that use the same diagnostic criteria for autism.

     These data expose the danger of not only setting out to prove, rather than to test, hypothesis but also presenting the data whether they are supportive or not. The full story has yet to unfold. In a timely BMJ newspiece, (5) Begg who is described as a leading virologist, calls for MMR research to be terminated on the basis of Taylor and co-workers' report and a non-peer-reviewed so-called analysis in Current Problems of Pharmacovigilance. Clearly there are some things that may end-up being terminated as a consequence of these events: research into the possible link between MMR, autism, and bowel disease is not one of them.

     Andrew J Wakefield

Departments of medicine and Histopathology, Royal Free and University College Medical School, Hampstead, London NW3 2PF, UK
     1. Lewin J, Dhillon AP, Sim, R, Mazure G, Pounder RE, Wakefield AJ.Persistent measles virus infection of the intestine: confirmation byimmunogold electron microscopy. Gut 1995; 36: 564-69.
     2. Chadwick N, Bruce IJ, Schepelman S, Pounder RE, Wakefield AJ.Measles virus RNA is not detected in inflammatory bowel disease using hybridcapture and reverse transcription followed by polymerase chain reaction. J Med Virol 1998; 70: 305-11.
     3. Montgomery SM, Morris DL, Pounder RE, et al. Paramyxovirus infections in childhood and subsequent inflammatory bowel disease.Gastroenterology 1999; 116: 796-803.
     4. Taylor B, Miller E, Farringdon CP, et al. MMR vaccine and autism: no epidemiological evidence for a casual association. Lancet 1999; 353:2026-29.
     5. Bower H. New research demolishes link between MMR vaccine and autism. BMJ 1999; 318: 1643. 

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