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Open Access Opinion

Mirroring everyday clinical practice in clinical trial design: a new concept to improve the external validity of randomized double-blind placebo-controlled trials in the pharmacological treatment of major depression

Emanuel Severus12*, Florian Seemüller2, Michael Berger2, Sandra Dittmann2, Michael Obermeier2, Andrea Pfennig1, Michael Riedel23, Sophia Frangou4, Hans-Jürgen Möller2 and Michael Bauer1

Author Affiliations

1 Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherstr. 74, 01307 Dresden, Germany

2 Department of Psychiatry and Psychotherapy, LMU Munich, Nussbaumstr. 7, 80336 Munich, Germany

3 Vinzenz von Paul Hospital, Schwenninger Str. 55, 78628 Rottweil, Germany

4 Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK

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BMC Medicine 2012, 10:67  doi:10.1186/1741-7015-10-67

Published: 2 July 2012

Abstract

Background

Randomized, double-blind, placebo-controlled trials constitute the gold standard in clinical research when testing the efficacy of new psychopharmacological interventions in the treatment of major depression. However, the blinded use of placebo has been found to influence clinical trial outcomes and may bias patient selection.

Discussion

To improve clinical trial design in major depression so as to reflect clinical practice more closely we propose to present patients with a balanced view of the benefits of study participation irrespective of their assignment to placebo or active treatment. In addition every participant should be given the option to finally receive the active medication. A research agenda is outlined to evaluate the impact of the proposed changes on the efficacy of the drug to be evaluated and on the demographic and clinical characteristics of the enrollment fraction with regard to its representativeness of the eligible population.

Summary

We propose a list of measures to be taken to improve the external validity of double-blind, placebo-controlled trials in major depression. The recommended changes to clinical trial design may also be relevant for other psychiatric as well as medical disorders in which expectations regarding treatment outcome may affect the outcome itself.

Keywords:
major depression; clinical trials; randomized controlled trials; psychopharmacology