Group sequential multi-arm multi-stage survival trial design with treatment selection.

Jianrong Wu, Yimei Li
Author Information
  1. Jianrong Wu: Biostatistics Shared Resource Facility, University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico, United States.
  2. Yimei Li: Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee, United States.

Abstract

Multi-arm trials are increasingly of interest because for many diseases; there are multiple experimental treatments available for testing efficacy. Several novel multi-arm multi-stage (MAMS) clinical trial designs have been proposed. However, a major hurdle to adopting the group sequential MAMS routinely is the computational effort of obtaining stopping boundaries. For example, the method of Jaki and Magirr for time-to-event endpoint, implemented in R package , requires complicated computational efforts to obtain stopping boundaries. In this study, we develop a group sequential MAMS survival trial design based on the sequential conditional probability ratio test. The proposed method is an improvement of the Jaki and Magirr's method in the following three directions. First, the proposed method provides explicit solutions for both futility and efficacy boundaries to an arbitrary number of stages and arms. Thus, it avoids complicated computational efforts for the trial design. Second, the proposed method provides an accurate number of events for the fixed sample and group sequential designs. Third, the proposed method uses a new procedure for interim analysis which preserves the study power.

Keywords

MeSH Term

Humans
Research Design
Clinical Trials as Topic
Computer Simulation
Models, Statistical
Treatment Outcome
Survival Analysis
Sample Size
Endpoint Determination
Data Interpretation, Statistical

Word Cloud

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