Severus, Emanuel and Seemüller, Florian and Berger, Michael and Dittmann, Sandra and Michael, Obermeier and Andrea, Pfennig and Michael, Riedel and Sophia, Frangou and Hans-Jürgen, Möller and Michael, Bauer
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.
In: BMC Medicine, Vol. 10:67: pp. 1-5
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
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, placebocontrolled
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