Randomized phase II/III confirmatory treatment selection design with a change of survival end points: Statistical design of Radiation Therapy Oncology Group 1216

随机 II/III 期确证性治疗选择设计,生存终点发生变化:放射治疗肿瘤学组 1216 的统计设计

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Abstract

BACKGROUND: To confirm the treatment effects of concurrent cetuximab plus docetaxel observed in Radiation Therapy Oncology Group (RTOG) 0234 and single out the effect of cetuximab, we designed RTOG 1216, a randomized phase II/III study, which uses an intermediate end point to select the best regimen for definitive testing of survival benefit. METHODS: In phase II, the best regimen should demonstrate statistically significant efficacy against the control with predefined advantage over the competing arm regarding disease-free survival (DFS). We evaluate operating characteristics of the randomized II/III group sequential design through simulations and numerical integrations under the null and various alternative hypotheses. RESULTS: Results show the randomized II/III design yields substantial savings on sample size and time with well-controlled type I and type II error rates. CONCLUSION: Overall, the proposed randomized II/III design has desirable properties that offer cost effectiveness, operational efficiency, and, most importantly, scientific innovation that can be considered for similar clinical research settings.

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