Magnitude of placebo response and response variance in antidepressant clinical trials using structured, taped and appraised rater interviews compared to traditional rating interviews

摘要

The high failure rate of antidepressant clinical trials is due in part to a high magnitude of placebo response and considerable variance in placebo response. In some recent trials enhanced patient interview techniques consisting of Structured Interview Guide for the Montgomery-Asberg Depression Rating Scale (SIGMA) interviews, audiotaping of patient interviews and 'central' appraisal with Rater Applied Performance Scale (RAPS) criteria have been implemented in the hope of increasing reliability and thus reducing the placebo response. However, the data supporting this rationale for a change in patient interview technique are sparse.We analyzed data from depressed patients assigned to placebo in antidepressant clinical trials conducted at a single research site between 2008 and 2012. Three trials included 34 depressed patients undergoing SIGMA depression interviews with taping and RAPS appraisal and 4 trials included 128 depressed patients using traditional interview methods.Using patient level data we assessed the mean decrease in total MADRS scores and the variability of the decrease in MADRS scores in trials using SIGMA interviews versus trials using traditional interviews.Mean decrease in total MADRS score was significantly higher in the 3 trials that used SIGMA interviews compared to the 4 trials using traditional interviews (M=13.0 versus 8.3, t(df=160)=2.04, p=0.047). Furthermore, trials using SIGMA had a larger magnitude of response variance based on Levene's test for equality of variance (SD=12.3 versus 9.4, F=7.3, p=0.008).The results of our study suggest that enhanced patient interview techniques such as SIGMA interviews, audiotaping and RAPS appraisal may not result in the intended effect of reducing the magnitude of placebo response and placebo variance.