UK autism review emphasizes importance of lay participation

A major review of autism published recently by the Medical Research Council (MRC) was commissioned by the UK Department of Health in March 2001, partly in response to public concerns raised by research alleging that MMR vaccination might be linked to an apparent increase in the numbers of children with autism. It was designed to be a wide-ranging review of research into different aspects of autism and other autism spectrum disorders (ASDs) — a set of neurodevelopmental disorders which results in impaired ability to communicate and interact with other people. One of the key aims was to identify gaps in knowledge and to make recommendations on future research strategy for the UK. Three groups of scientists examined the research evidence and assessed the strength of research-based knowledge in epidemiology and case definition, physiology and infection, and psychology and behavior. For the first time in an MRC research review there was extensive input from lay people from the outset, putting forward questions that reflected concerns raised by parents of children with autism.The report found that autism was more prevalent than had previously been thought, with around six in 1,000 young children having an autism spectrum disorder. Carol Dezateux, clinical reader in epidemiology at the Institute of Child Health at Great Ormond Street NHS Trust and chair of the review's epidemiology subgroup said: "This estimate makes autism spectrum disorders far more common than was previously generally recognized." Most of the apparent increase was considered to have resulted from changes in case definition, as well as increased awareness of the condition. Not surprisingly, the lay members of the review panel were particularly interested to know more about what might cause autism. The review concluded that it was most likely that autism results from several causes but argued that the strongest evidence was for a genetic component. The reviewers suggested: "It seems likely that several genes interact to create susceptibility to the disorder. The interplay between genetic and environmental factors is also likely to play a key role but the nature of these interactions is not yet known." These factors could all affect the same brain systems, or could impede development through disruption of the different abilities necessary for social and communicative development. In a few cases, various single gene disorders and chromosomal abnormalities have been reported in individuals with ASDs.Importantly — in terms of public interest — the review concluded that current evidence from epidemiological studies did not support the proposed link of MMR to autism spectrum disorders. The MMR controversy was triggered initially by a study published in 1998, which claimed to show that MMR was linked to autism and intestinal abnormalities. The study assessed 12 children who were referred to the pediatric gastroenterology unit at London's Royal Free Hospital with a history of normal development followed by loss of acquired skills, including language together with diarrhea and abdominal pain. The researchers reported that the parents associated the onset of behavioral symptoms with MMR vaccination in 8 of the 12 children, and with measles infection in one child and otitis media in another. All 12 children had intestinal abnormalities, ranging from lymphoid nodular hyperplasia to aphthoid ulceration. Nine of the children were judged to have autism. The researchers concluded that they had identified associated gastrointestinal disease and development regression in a group of previously normal children, which was generally associated in time with possible environmental triggers. They noted: "We did not prove an association between measles, mumps and rubella vaccine and the syndrome described." But, Andrew Wakefield, who was a member of the research team, went out on a limb by suggesting that there might be a link and that parents should consider single vaccinations for measles, mumps and rubella rather than the combined triple vaccine.The hypothesis was based on the 'opioid excess' theory of autism, suggesting that autistic disorders result from the incomplete breakdown and excessive absorption of gut-derived peptides from foods. These peptides may exert central opioid effects, leading to disruption of normal neuroregulation and brain development. The Royal Free group suggested that impaired intestinal function could permit increased permeability to exogenous peptides. But, the new MRC review found no evidence to support this hypothesis, based on analysis of a range of studies from the UK, North America and Finland. One of the studies they considered was a large epidemiological study from a different group at the Royal Free, which contradicted the alleged link (Lancet 1999, 353:2026-2029). This study identified children with autism born since 1979 in eight North Thames health districts. Information from clinical records was linked to immunization data held on the child health computing system. The team looked for evidence of a change in the incidence or age at diagnosis associated with the introduction of MMR vaccination to the UK in 1988. Results showed no sudden 'step up' or change in the trend of autism prevalence after the introduction of MMR vaccination. There was no difference in age at diagnosis between the cases vaccinated before or after 18 months of age and those never vaccinated.A large, prospective follow-up of the MMR vaccination programme in Finland published in January 2001 demonstrated that serious adverse events were rare and greatly outweighed the risks of disease (Pediatr Infect Dis J 2000, 19:1127-1134). The study followed 1.8 million individuals for 14 years from the start of the MMR vaccination programme in 1982. By the end of 1996, almost three million doses of the vaccine had been given, and 173 potentially serious reactions had been recorded as having possibly been caused by the vaccine. The most common event was febrile seizure.The study's authors, from the Hospital for Children and Adolescents in Helsinki, reported that 45% of these adverse events proved to have probably been caused by some other factor, giving an incidence of serious adverse events of 3.2 per 100,000 vaccine doses. No cases of inflammatory bowel disease or autism were detected. The study was criticised by groups concerned about MMR who argued that it did not look specifically for these conditions. However the researchers noted: "The study was not designed to look for any specific adverse events, but to record any problems reported, of any kind."For the future, the MRC report recommended building on the existing strengths of autism research by improving co-ordination between different research disciplines and improving research training in service settings. It also called for more research on the definition of autism spectrum disorders, especially in adults, noting: "This is crucial both for future research and for provision of services for those with ASDs." More basic biological research studies were also suggested, acknowledging that there is still a lot of uncertainty about the biological processes involved in autism, both in the brain and other organs. There is some hope that imaging studies could contribute significantly to improving understanding of the pathophysiology of autism. Functional brain imaging in people with ASD has found under-activation in areas associated with planning and control of complex action, and in areas associated with processing socio-emotional information. Large population studies were also proposed by the review, to address questions about environmental risks and their interaction with genetic factors. The MRC is now discussing with the Department of Health how to act on these proposals. Dezateux pointed out that progress in autism research would depend on adequate funding. One of the lay representatives on the review, Judith Barnard, who is Director of Policy and Public Affairs at the National Autistic Society, warned: "It's vital we understand more about the causes of this devastating disability so that children and adults are given the help they need at the earliest opportunity. We hope that the government will recognise the need to fund research into autism so that the recommendations in this report can be implemented to improve the lives of people with autism and their families."And how did the lay participation in the review process work out? The lay members of the review panel tended to raise questions and issues that were quite different to those considered important by the scientist members. Dezateux explained: "The lay members were all fired up by speculation, largely based on grey, unpublished research. But these issues were important to them — and it was useful to be able to discuss the scientific evidence together." "The participation in this review of people with autism, their carers and people with experience of support groups has enriched both the process and its outputs. Further partnerships which give lay organizations access to scientific expertise and give scientists to lay perspectives can only be of benefit," suggested Eve Johnstone, who is chair of the MRC's Neurosciences and Mental Health Research Board in addition to chair of the autism review. The review group as a whole agreed: "We should build on the researcher-lay-funder partnership that was indispensable to this review." They argued that there should be efforts to improve consumer involvement in the design, conduct and dissemination of research — as a means to enhancing its quality and relevance to society.

UK autism review emphasizes importance of lay participation

Lay participation in medical research review illustrates the differing perceptions that scientists and the public have of each other.

Interested in reading more?

Become a Member of