Abstract
Decisions concerning treatment changes pervade the management of chronic psychiatric disorders that resist definitive cure, yet empirical evidence for the comparative clinical effectiveness of treatment strategies remains underdeveloped. In this paper we exploit the example of psychosis following substance use to illustrate some new developments in clinical trials design that can provide the most solid evidence base for defining successful strategies. The intent is to explore the strengths and limitations of the methodological approach through a meaningful clinical example, with an emphasis on concepts and issues. Both methodology and clinical science are overviewed. Psychopharmacology Bulletin.
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