Placebo or active control trials of antipsychotic drugs?

W. Wolfgang Fleischhacker, P. Czobor, Martina Hummer, Georg Kemmler, Ralf Kohnen, Jan Volavka

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

The placebo-controlled trial has been the standard method to demonstrate efficacy and safety of antipsychotic drugs. We reviewed the scientific and ethical advantages and disadvantages of the placebo-controlled trial and an alternative method, the active- control trial, focusing more specifically on the active-control noninferiority trial. Recent meta-analyses indicate that a therapeutic dose of second-generation antipsychotic will very likely be statistically superior to placebo in an adequate trial, and that the average improvement of schizophrenia symptoms in a placebo arm will be small. These findings strengthen the scientific and ethical justification for the active-control noninferiority trial. New drugs in the pharmacotherapy for schizophrenia are often claimed to differ from their marketed competitors in their safety profile rather than in antipsychotic efficacy. Thus, in many cases, it appears sufficient to demonstrate mere noninferiority (rather than superiority) of antipsychotic efficacy in comparison with a standard antipsychotic. The active-control noninferiority trial is suitable for such demonstration. Sample size requirements for various equivalence margins in noninferiority trials are provided. Scientific and ethical arguments should lead to a more frequent use of the active-control noninferiority trial design.

Original languageEnglish
Pages (from-to)458-464
Number of pages7
JournalArchives of General Psychiatry
Volume60
Issue number5
DOIs
Publication statusPublished - May 1 2003

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Antipsychotic Agents
Placebos
Schizophrenia
Safety
Sample Size
Meta-Analysis
Drug Therapy
Pharmaceutical Preparations
Therapeutics

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Fleischhacker, W. W., Czobor, P., Hummer, M., Kemmler, G., Kohnen, R., & Volavka, J. (2003). Placebo or active control trials of antipsychotic drugs? Archives of General Psychiatry, 60(5), 458-464. https://doi.org/10.1001/archpsyc.60.5.458

Placebo or active control trials of antipsychotic drugs? / Fleischhacker, W. Wolfgang; Czobor, P.; Hummer, Martina; Kemmler, Georg; Kohnen, Ralf; Volavka, Jan.

In: Archives of General Psychiatry, Vol. 60, No. 5, 01.05.2003, p. 458-464.

Research output: Contribution to journalArticle

Fleischhacker, WW, Czobor, P, Hummer, M, Kemmler, G, Kohnen, R & Volavka, J 2003, 'Placebo or active control trials of antipsychotic drugs?', Archives of General Psychiatry, vol. 60, no. 5, pp. 458-464. https://doi.org/10.1001/archpsyc.60.5.458
Fleischhacker, W. Wolfgang ; Czobor, P. ; Hummer, Martina ; Kemmler, Georg ; Kohnen, Ralf ; Volavka, Jan. / Placebo or active control trials of antipsychotic drugs?. In: Archives of General Psychiatry. 2003 ; Vol. 60, No. 5. pp. 458-464.
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