Workshop 3: Study design

The basic design of NBAAD studies is governed by FDA requirements for three phases of evaluation. The objectives of such studies are dependent, therefore, on the phase of drug study as well as the uniqueness of the study drug and the subject population. Objectives should be clearly stated before the study is started. Selection of the subject population requires a careful baseline evaluation during a prescreening observation period and a clear definition of subject characteristics at the time of the study. Double-blind controlled studies are essential. Active treatment controls are required in Phase III studies, but these do not have to act through the same mechanism as the study drug. Parallel studies are preferable to crossover studies, unless lack of carryover effect can be assured. Both multicenter and singlecenter studies are appropriate in different phases of study, but the number of patients included at each study center should be of sufficient quantity to allow for individual evaluation at each center. Phase III studies should be divided into a prestudy control period ("run-in"), which in a single-blind fashion can identify placebo responders, ensure compliance, and stabilize treatment regimens, as well as an experimental period, which should be at least 12 weeks in duration. The method of handling special and unexpected events (such as environmental interactions) during the study should be established beforehand. These recommendations for the design of protocols to study NBAAD are intended to allow for maximum flexibility within the framework of the basic requirements for a well-designed study. In so doing, it is anticipated that they will be appropriate not only for a wide range of currently studied drugs, but will also be relevant to the study of new drugs with different mechanistic concepts in the future.