title: Suspension of accrual in phase II cancer clinical trials.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Yimei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biostatistics & Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Mick
authors.affiliation: Department of Biostatistics & Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Heitjan
mesh_terms: D017322:Clinical Trials, Phase II as Topic / Q000379:methods*; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D006801:Humans; D009369:Neoplasms / Q000628:therapy*; D018579:Patient Selection; D012107:Research Design
keywords: Accrual; cancer; clinical trial; phase II; suspension