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Maintenance efficacy designs in psychiatry: Randomized discontinuation trials – enriched but not better

  • S. N. Ghaemi (a1) and Harry P. Selker (a2) (a3)

Abstract

Introduction

Although classical randomized clinical trials (RCTs) are the gold standard for proof of drug efficacy, randomized discontinuation trials (RDTs), sometimes called “enriched” trials, are used increasingly, especially in psychiatric maintenance studies.

Methods

A narrative review of two decades of experience with RDTs.

Results

RDTs in psychiatric maintenance trials tend to use a dependent variable as a predictor: treatment response. Treatment responders are assessed for treatment response. This tautology in the logic of RDTs renders them invalid, since the predictor and the outcome are the same variable. Although RDTs can be designed to avoid this tautologous state of affairs, like using independent predictors of outcomes, such is not the case with psychiatric maintenance studies

Further, purported benefits of RDTs regarding feasibility were found to be questionable. Specifically, RDTs do not enhance statistical power in many settings, and, because of high dropout rates, produce results of questionable validity. Any claimed benefits come with notably reduced generalizability.

Conclusions

RDTs appear to be scientifically invalid as used in psychiatric maintenance designs. Their purported feasibility benefits are not seen in actual trials for psychotropic drugs. There is warrant for changes in federal policy regarding marketing indications for maintenance efficacy using the RDT design.

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Copyright

This is an Open Access article, distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is unaltered and is properly cited. The written permission of Cambridge University Press must be obtained for commercial re-use or in order to create a derivative work.

Corresponding author

*Address for correspondence: S. N. Ghaemi, Mood Disorders Program, Department of Psychiatry, Tufts Medical Center, Tufts University School of Medicine, 800 Washington St., Boston, MA 02111, USA. (Email: nghaemi@tuftsmedicalcenter.org)

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Maintenance efficacy designs in psychiatry: Randomized discontinuation trials – enriched but not better

  • S. N. Ghaemi (a1) and Harry P. Selker (a2) (a3)

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