Randomized controlled trials for schizophrenia: study designs targeted to distinct goals.

Randomized controlled trials for antipsychotic drugs have a variety of design features suited to diverse purposes. Efficacy (or explanatory) trials seek to establish if a drug can reduce psychotic symptoms under ideal circumstances. To isolate drug effects, researchers enroll carefully selected patients. Specialized research personnel use rating scales of symptoms that are sensitive to drug effects as the study primary outcomes. Large simple trials (LSTs) are conducted at typical treatment settings with usual clinical personnel and enroll large numbers of participants so small but clinically important differences between treatment options can be detected. LSTs focus narrowly on clearly defined, patient-oriented outcomes. To some extent, practical trials can be conceptualized as hybrids of efficacy and large simple trials. Practical trials provide independent evidence to inform decision makers about the everyday effectiveness of clinically relevant alternative interventions. Practical trial researchers include a heterogeneous population of patients and collect data on a broad range of meaningful health outcomes at many types of practice settings intended to represent usual treatment. The designers of practical trials make trade-offs between internal validity, external validity, the breadth of issues addressed, and the ability to detect small differences. The different objectives of trials should be considered in the interpretation of the complete body of randomized evidence on antipsychotic drugs.