The effect of elective sham dose escalation on the placebo response during an antimuscarinic trial for overactive bladder symptoms.

Abstract

We analyzed the effects of baseline symptom severity and placebo response magnitude on the decision to dose escalate in a 12-week, randomized, double-blind, flexible dose antimuscarinic trial of subjects with overactive bladder symptoms. Data from the placebo arm of the trial were used for this post hoc analysis. Subjects could elect dose escalation at week 2. Those in the placebo arm received sham escalation. Most placebo treated subjects who continued to week 2 elected dose escalation (75% or 325 of 435). Overactive bladder symptoms at baseline were similar between placebo escalators and nonescalators. Nonescalators showed a significantly larger placebo response than escalators, as measured by improvements in bladder diary end points and patient reported outcomes, and by the incidence rate of adverse events before and after sham escalation. These findings suggest that the decision to dose escalate among placebo treated subjects is independent of baseline symptom severity but may be influenced by the placebo response magnitude for efficacy assessment and adverse events. Placebo nonescalators showed a rapid, large placebo response while placebo escalators showed a smaller placebo response even after sham escalation. These observations may have important implications for the design and interpretation of flexible dose trials using a placebo control.