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Does placebo help establish equivalence in trials of new antidepressants?

Published online by Cambridge University Press:  16 April 2020

C. Barbui ,
A. Violante  and
S. Garattini
C. Barbui
Affiliation:
Laboratory of Epidemiology and Social Psychiatry, WHO Collaborating Centre for Research and Training in Mental Health, Istituto di Ricerche Farmacologiche ‘Mario Negri’,Milan, Italy
A. Violante
Affiliation:
Unità Operativa di Farmacoepidemiologia Azienda USL Modena,Italy
S. Garattini*
Affiliation:
Laboratory of Epidemiology and Social Psychiatry, WHO Collaborating Centre for Research and Training in Mental Health, Istituto di Ricerche Farmacologiche ‘Mario Negri’,Milan, Italy
*
*Correspondence and reprints: Corrado Barbui MD, Istituto di Ricerche Farmacologiche ‘Mario Negri’, Via Eritrea 62, 20157 Milan, Italy
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Summary

Clinical trials of new antidepressants usually compare a new drug to a reference antidepressant and to a placebo. The placebo is intended to validate the trial in the case of a no-difference outcome, i.e., it helps in assessing equivalence. The aim of the present paper is to test whether placebo has indeed helped establish equivalence of effect in comparative trials of new antidepressants. We carried out an example of sample size determination first in a trial to show a difference between the new and control drug, and second in a trial to assess equivalence between two competing drugs. Finally, we retrospectively calculated the maximum difference accepted as equivalence of effect in published trials of new antidepressants. Assuming a response rate to antidepressants of 70%, 294 subjects for each treatment group are needed to show a 10% difference between two antidepressant drugs and more than 1,300 to assess equivalence at a 5% level of δ, the maximum difference acceptable as equivalence of effect. The level of δ in published trials of new antidepressants ranges between 12 and 43%, suggesting they cannot claim to demonstrate equivalence of effect. Therefore, the presence of a placebo arm for comparison didn’t help establish whether both drugs really worked the same way. Comparative trials of new antidepressants should adopt a two-arm design, a suitable number of patients and a high standard in the experimental design in order to minimise possible control-event rate variation.

Keywords

antidepressant drugsclinical trialsplacebotrial methodology
Type
Original article
Information
European Psychiatry , Volume 15 , Issue 4 , June 2000 , pp. 268 - 273
Copyright
Copyright © Éditions scientifiques et médicales Elsevier SAS 2000

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