Keith Wheatley and colleagues make the case that most trials of drug treatment for Parkinson's disease have crucial methodological faults—and provide little reliable evidence on differences between classes of drugs

Parkinson's disease is one of the commonest causes of disability in older people, with over 100 000 patients in the United Kingdom and at least 8000 new cases diagnosed annually. Prevalence and incidence will both increase with the ageing population and the reduction in competing causes of mortality such as stroke and coronary heart disease.1 No cure currently exists, and medical treatment is directed towards alleviating symptoms.2 Levodopa relieves symptoms in most patients with Parkinson's disease, but long term use of levodopa is associated with motor complications such as involuntary movements (dyskinesias), along with a shortened response to each dose (wearing-off phenomenon) and unpredictable “on-off” fluctuations. A number of other drugs have been used,3 either alone or with reduced doses of levodopa, in an attempt to delay the onset of motor complications in early Parkinson's disease or to control complications once they have developed. These agents have primarily been from three classes of drug: dopamine agonists, monoamine oxidase type B inhibitors, and catechol-O-methyltransferase inhibitors.

Many randomised controlled trials have evaluated these drugs, but uncertainty about their relative effectiveness remains. This review assesses the methods used in these trials to reveal the quality of the existing evidence base.