Takanobu Yamamoto, Soichiro Yoshida, Shugo Yajima, Hiroshi Fukushima, Yosuke Yasuda, Yuma Waseda, Hiroyuki Sato, Akihiro Hirakawa, Hiroyuki Honda, Yoshinobu Komai, Tomohiro Matsuo, Naoki Wada, Hitoshi Masuda, Yasuhisa Fujii
Bayesian cross-trial synthesis demonstrates a high probability that vibegron improves key OAB voiding-diary outcomes at Week 12. By explicitly quantifying the probability of exceeding clinically interpretable decision thresholds, this approach provides a transparent assessment of both the direction and magnitude of treatment effects, facilitating clinically interpretable decision-making.
OBJECTIVES: To synthesize published placebo-controlled trials of vibegron monotherapy for overactive bladder (OAB) and quantify posterior probabilities of benefit and decision-threshold exceedance.
METHODS: We extracted published placebo-adjusted least-squares mean differences at Week 12 from three randomized, double-blind, placebo-controlled Phase III trials evaluating vibegron monotherapy (Japan Phase III trial, Korea bridging study [50 mg], and EMPOWUR trial [75 mg]) for four voiding-diary endpoints: micturitions/day, urgency episodes/day, urgency urinary incontinence (UUI) episodes/day, and voided volume (mL). For each endpoint, a Bayesian normal-normal random-effects model estimated the pooled mean effect and between-trial heterogeneity and calculated posterior probabilities of benefit and of exceeding thresholds predefined in this analysis.
RESULTS: Pooled mean effects (95% credible intervals) favored vibegron across all four voiding-diary endpoints: micturitions/day (-0.76, -1.33 to -0.28), urgency episodes/day (-0.69, -1.35 to -0.22), UUI episodes/day (-0.44, -0.93 to -0.03), and voided volume (+24.09 mL, 15.78-32.51). The posterior probabilities of benefit were 99.5%, 99.3%, 98.0%, and > 99.9%, respectively. The probabilities of exceeding thresholds were as follows: for micturitions/day, ≤ -0.5: 90.3% and ≤ -1.0: 14.2%; for urgency episodes/day, ≤ -0.5: 82.8% and ≤ -1.0: 12.7%; for UUI episodes/day, ≤ -0.3: 81.8% and ≤ -0.5: 35.4%; and for voided volume, ≥ +10 mL: 99.5%, ≥ +20 mL: 88.4%, and ≥ +30 mL: 5.8%.
CONCLUSIONS: Bayesian cross-trial synthesis demonstrates a high probability that vibegron improves key OAB voiding-diary outcomes at Week 12. By explicitly quantifying the probability of exceeding clinically interpretable decision thresholds, this approach provides a transparent assessment of both the direction and magnitude of treatment effects, facilitating clinically interpretable decision-making.