Ecological studies cannot answer main question

EDITOR—Kaye et al undertook an ecological study comparing the time trend in measles, mumps, and rubella (MMR) vaccine coverage with the time trend in diagnoses of autism.1 They found a marked increase in the incidence of codes for autism in children's electronic general practice records over 11 years.

We agree with their conclusion that MMR cannot be the cause of this observed increase since the vaccine coverage remained constant over the same time. There have been changes in the classification of autistic diseases and in the likelihood of case ascertainment in recent years, and a more rigorous review of cases may clarify whether some of the increase was due to alterations in diagnostic practice.2 Only 81% of cases were reported to have been referred to a specialist, raising questions about the validity of the diagnoses used by Kaye et al. Children with medical conditions present from birth and known to be associated with an increased risk of autism (fragile X disorder, tuberous sclerosis, phenylketonuria, and congenital rubella) were not excluded.

The failure to find an association between the time trends in vaccine coverage and the incidence of autism codes in children's electronic general practice records does not exclude a causal association. Whether exposure to MMR vaccination increases the risk of autism is of great public health importance and can be usefully investigated using the general practice research database. We have been funded by the United Kingdom Medical Research Council to undertake an investigation of the causes of autism, including an assessment of the potential role of MMR vaccine using case-control and case series approaches. The electronic general practice records in the database will be supplemented by a full record review of all cases and, subject to ethical approval, questionnaires to parents of both affected children …