Innovations in Clinical Research Design and Conduct in Psychiatry: Shifting to Pragmatic Approaches

Marks, David M; Thanaseelan, J; Pae, Chi Un

Abstract

The classically structured clinical trial does not offer enough flexibility to make use of continuously emerging knowledge that is generated as the trial progresses. In this regard, there are consistent issues impeding effective psychiatric research, including limitations in efficiency, difficulty demonstrating significant differences between treatment arms, poor external validity, and ethical constraints. For example, research in the field of psychiatry shows that it is growing increasingly more challenging to demonstrate superiority of interventions to placebo in part related to the increasing placebo response rates. Various design innovations and other tricks of the trade have surfaced to improve sensitivity towards detecting drug-placebo differences and reduce sources of bias in psychiatric research. Diverse strategies have been developed to address these obstacles and improve the outcomes of clinical research in psychiatry. The current review highlights many of these innovations and describes examples of their practical use, mainly focusing on the study design and conduct perspectives. In the study design issues, adaptive, equipoise stratified, sequential parallel and effectiveness design will be explored. The proper strategies for pragmatic and ethical conduction of clinical trials will be also discussed in-depth.