Yimei Li1, Rosemarie Mick2, Daniel F Heitjan2. 1. Department of Biostatistics & Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA yimeili@mail.med.upenn.edu. 2. Department of Biostatistics & Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Abstract
PURPOSE: Phase II cancer clinical trial designs commonly incorporate an interim analysis for lack of efficacy. To strictly and ethically implement such designs, one should suspend accrual in cases where pending patient outcomes can affect early termination decisions. This article aims to evaluate various options for accrual suspension and illustrate how the suspension strategy affects operating characteristics of the trial. METHODS: We define a strict suspension strategy for determining whether one should continue, suspend, or restart accrual at any point within the trial. The strategy is compared to a naive implementation of suspension and a strategy of no suspension. We evaluate the methods' operating characteristics by simulation. RESULTS: The suspension strategy has little effect on type I error, power, and early termination probability. Methods that involve stricter suspension policies generally lead to smaller but longer trials. Differences across strategies are substantial when the ratio of enrollment rate to outcome availability rate is high. CONCLUSION: The suspension strategy is most relevant in trials that accrue rapidly and require lengthy observation of each subject. The choice of suspension strategy involves a tradeoff between the cost of implementing a potentially complex suspension algorithm in real time versus the cost of enrolling more patients and exposing them to a potentially toxic and ineffective treatment regimen.
PURPOSE: Phase II cancer clinical trial designs commonly incorporate an interim analysis for lack of efficacy. To strictly and ethically implement such designs, one should suspend accrual in cases where pending patient outcomes can affect early termination decisions. This article aims to evaluate various options for accrual suspension and illustrate how the suspension strategy affects operating characteristics of the trial. METHODS: We define a strict suspension strategy for determining whether one should continue, suspend, or restart accrual at any point within the trial. The strategy is compared to a naive implementation of suspension and a strategy of no suspension. We evaluate the methods' operating characteristics by simulation. RESULTS: The suspension strategy has little effect on type I error, power, and early termination probability. Methods that involve stricter suspension policies generally lead to smaller but longer trials. Differences across strategies are substantial when the ratio of enrollment rate to outcome availability rate is high. CONCLUSION: The suspension strategy is most relevant in trials that accrue rapidly and require lengthy observation of each subject. The choice of suspension strategy involves a tradeoff between the cost of implementing a potentially complex suspension algorithm in real time versus the cost of enrolling more patients and exposing them to a potentially toxic and ineffective treatment regimen.
Authors: Andre Goy; Rajni Sinha; Michael E Williams; Sevgi Kalayoglu Besisik; Johannes Drach; Radhakrishnan Ramchandren; Lei Zhang; Sherri Cicero; Tommy Fu; Thomas E Witzig Journal: J Clin Oncol Date: 2013-09-03 Impact factor: 44.544
Authors: Ranjana H Advani; Sandra J Horning; Richard T Hoppe; Sarah Daadi; John Allen; Yasodha Natkunam; Nancy L Bartlett Journal: J Clin Oncol Date: 2014-02-10 Impact factor: 44.544