Feasibility of reducing the duration of placebo-controlled trials in schizophrenia research.
Use of placebo-controlled trials in medical and psychiatric research has been controversial, although a consensus is emerging about conditions under which placebo-controlled trials are ethical. In schizophrenia research, the paradigm of slow onset of antipsychotic effects has led to a model in which placebo-controlled trials of 6-8 weeks duration have been used to demonstrate efficacy. Recent evidence that the largest symptom reductions are typically seen in the first weeks of treatment suggests that shorter placebo-controlled studies to demonstrate antipsychotic efficacy are possible. In a pilot study of the feasibility of shortening placebo-controlled studies, we reanalyzed data from placebo-controlled registry trials of olanzapine and risperidone and found that trials as short as 4 weeks could have similar power to longer term 6-8 week studies, given the estimated time course of treatment effects. Although fuller evaluation is required, the results suggest future antipsychotic trials could be shortened from 6-8 weeks to 3-4 weeks with a relatively low increase in sample size requirements. Shortening placebo-controlled trials would reduce patient burden and ethical objections to prolonged administration of placebo and reduce potential bias due to high dropout rates in longer clinical trials.
McMahon
Robert P
RP
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland Baltimore Medical School, Baltimore, MD, USA.
Kelly
Deanna L
DL
Boggs
Douglas L
DL
Li
Lan
L
Hu
Qiaoyan
Q
Davis
John M
JM
Carpenter
William T
WT
D001569:Benzodiazepines / Q000627:therapeutic use*; D016022:Case-Control Studies; D026690:Ethics, Clinical; D005240:Feasibility Studies; D006220:Haloperidol / Q000627:therapeutic use*; D006801:Humans; D000077152:Olanzapine; D010352:Patient Dropouts / Q000706:statistics & numerical data; D010865:Pilot Projects; D016032:Randomized Controlled Trials as Topic; D012042:Registries; D018967:Risperidone / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy* / Q000453:epidemiology; D013997:Time Factors
D001569:Benzodiazepines; D006220:Haloperidol; D018967:Risperidone; D000077152:Olanzapine