Factors influencing efficacy endpoints in clinical trials for new oral medicinal treatments for overactive bladder: a systematic literature review and meta-analysis.

PURPOSE: Overactive bladder (OAB) is a symptom-based disease; therefore, clinical trials to evaluate treatments for OAB employ a range of efficacy endpoints. Since factors that influence efficacy endpoints can affect trial outcomes, their identification could aid in the design of future OAB clinical trials. We investigated factors influencing different efficacy endpoints used in clinical trials with OAB patients and examined their characteristics to determine future clinical trial strategies for new medicinal treatments for OAB.

METHODS: Data from placebo-controlled double-blind trials in patients with OAB were extracted via a systematic literature review. The integrated differences for efficacy endpoints were calculated. Heterogeneity was assessed using the Q statistic and I2 statistic. Factors influencing efficacy endpoints were identified through univariate and multivariate meta-regression analyses.

RESULTS: Forty-one controlled trials were analyzed. Substantial heterogeneity between studies was observed for each efficacy endpoint (P > 0.001, I2  > 70%). We found with multivariate meta-regression analysis that period of recording in a bladder diary and year of publication were significantly likely to influence the change from baseline in the mean number of urgency episodes in 24 h, year of publication and gender were significantly likely to influence the change from baseline in the mean number of micturitions in 24 h, and gender was significantly likely to influence the change from baseline in the mean volume voided per micturition. In contrast, there were no factors significantly associated with change from baseline in the mean number of incontinence episodes in 24 h.

CONCLUSIONS: We identified that change from baseline in the mean number of incontinence episodes in 24 h should serve as a relatively stable endpoint. In contrast, we identified factors influencing other endpoints, and the identified factors should be taken into account when planning and conducting future clinical trials.