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.
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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors: Emanuel
authors: E
authors: Severus
authors: Florian
authors: F
authors: Seemüller
authors: Michael
authors: M
authors: Berger
authors: Sandra
authors: S
authors: Dittmann
authors: Michael
authors: M
authors: Obermeier
authors: Andrea
authors: A
authors: Pfennig
authors: Michael
authors: M
authors: Riedel
authors: Sophia
authors: S
authors: Frangou
authors: Hans-Jürgen
authors: HJ
authors: Möller
authors: Michael
authors: M
authors: Bauer
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D015990:Placebo Effect; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D015203:Reproducibility of Results; D012107:Research Design; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents