Advisory Committee Chair
Jeff M Szychowski
Advisory Committee Members
Nengjun Yi
Inmaculada Aban
Alan Thevenet N Tita
Andres Azuero
Document Type
Dissertation
Date of Award
2017
Degree Name by School
Doctor of Philosophy (PhD) School of Public Health
Abstract
Multi-arm clinical trials comparing several treatments against a common control are more efficient than traditional multiple two-arm trials. Several flexible multi-arm designs which utilize the closed test procedure for strong familywise error rate control have been proposed to allow treatment selection and sample size re-estimation (SSR) at the interim analysis. Because of the interdependence among hypothesis tests for each treatment induced by the closed test procedure, SSR methods for two-arm trials are not directly applicable to multi-arm trials. Further, there is limited literature on methods for SSR in multi-arm trials. In paper 1, we derive SSR procedures based on the conditional power approach in the context of confirmatory two-stage multi-arm trials with normal outcomes for three flexible designs: the inverse normal combination test (INC), Fisher’s combination test (FiC) and the flexible group sequential design (FGS). We conduct extensive simulation studies to evaluate the performance of SSR based on the conditional power approach using both the planned effect size and the estimated interim effect size, considering two treatment selection rules. We find that FGS and INC outperform FiC in terms of power and additional sample size needed when selecting the best treatment; FGS has the highest power while INC has the smallest sample size when keeping all promising treatments. In paper 2, we extend the SSR procedure to binary outcomes and investigate the operating characteristics of SSR in the three designs. The relative performance of the three designs is similar to that in paper 1. In paper 3, we apply the SSR procedure to the data collected from a trial of higher-dose oxytocin at delivery to demonstrate a practical example of a multi-arm study that may have benefited from the SSR methods examined in this analysis.
Recommended Citation
Li, Yan, "Sample Size Re-Estimation for Confirmatory Two-Stage Multi-Arm Trials With Normal and Binary Outcomes" (2017). All ETDs from UAB. 2276.
https://digitalcommons.library.uab.edu/etd-collection/2276
