Site variability in treatment outcome in antidepressant trials.
OBJECTIVE
Site-specific differences in treatment outcome during multisite antidepressant drug trials may contribute to a negative or failed clinical trial. As part of a five-site, long-term, double-blind, placebo-controlled, relapse prevention trial with fluoxetine in major depression, the authors examined site-specific variability in outcome ratings.


METHODS
Data from 390 patients with major depression who participated in a 64-week, placebo-controlled trial were retrospectively analyzed. chi 2 Analyses and Kaplan-Meier survival estimates were used to examine site-specific differences in relapse rates during 14 weeks of maintenance treatment following randomization to fluoxetine or placebo after remission with fluoxetine treatment.


RESULTS
Results from chi 2 analysis (P < .001) and Kaplan-Meier survival rates (P < .001) following randomization to placebo after 12 weeks of fluoxetine treatment showed a fluoxetine superiority over placebo among all five sites combined. Individually, however, only three of the five sites (60%) were able to distinguish fluoxetine superiority. In contrast, there was no fluoxetine versus placebo difference observed among all five sites after randomization following 26 weeks of fluoxetine treatment (P = .11, Fisher's exact test). However, one site (20%) individually could still distinguish a drug versus placebo difference (P < .05).


CONCLUSIONS
Analyses were performed retrospectively, with individual sites not specifically powered to distinguish a drug-placebo difference.


CONCLUSIONS
Substantial site differences were observed in the ability to distinguish drug superiority over placebo, and this variability may contribute to a negative or failed clinical drug trial.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D018849:Controlled Clinical Trials as Topic / Q000379:methods* / Q000706:statistics & numerical data; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000401:mortality; D004311:Double-Blind Method; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D055502:Secondary Prevention; D016019:Survival Analysis; D016896:Treatment Outcome
D000928:Antidepressive Agents; D005473:Fluoxetine