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BMC Medicine
Published in: BMC Medicine 1/2012

Open Access 01-12-2012 | 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

Authors: Emanuel Severus, Florian Seemüller, Michael Berger, Sandra Dittmann, Michael Obermeier, Andrea Pfennig, Michael Riedel, Sophia Frangou, Hans-Jürgen Möller, Michael Bauer

Published in: BMC Medicine | Issue 1/2012

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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.
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Metadata
Title
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
Authors
Emanuel Severus
Florian Seemüller
Michael Berger
Sandra Dittmann
Michael Obermeier
Andrea Pfennig
Michael Riedel
Sophia Frangou
Hans-Jürgen Möller
Michael Bauer
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2012
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/1741-7015-10-67

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