Exploring the benefits of adaptive sequential designs in time-to-event endpoint settings

Sarah C. Emerson, Kyle D. Rudser, Scott S. Emerson

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Sequential analysis is frequently employed to address ethical and financial issues in clinical trials. Sequential analysis may be performed using standard group sequential designs, or, more recently, with adaptive designs that use estimates of treatment effect to modify the maximal statistical information to be collected. In the general setting in which statistical information and clinical trial costs are functions of the number of subjects used, it has yet to be established whether there is any major efficiency advantage to adaptive designs over traditional group sequential designs. In survival analysis, however, statistical information (and hence efficiency) is most closely related to the observed number of events, while trial costs still depend on the number of patients accrued. As the number of subjects may dominate the cost of a trial, an adaptive design that specifies a reduced maximal possible sample size when an extreme treatment effect has been observed may allow early termination of accrual and therefore a more cost-efficient trial. We investigate and compare the tradeoffs between efficiency (as measured by average number of observed events required), power, and cost (a function of the number of subjects accrued and length of observation) for standard group sequential methods and an adaptive design that allows for early termination of accrual. We find that when certain trial design parameters are constrained, an adaptive approach to terminating subject accrual may improve upon the cost efficiency of a group sequential clinical trial investigating time-to-event endpoints. However, when the spectrum of group sequential designs considered is broadened, the advantage of the adaptive designs is less clear.

Original languageEnglish (US)
Pages (from-to)1199-1217
Number of pages19
JournalStatistics in Medicine
Issue number11
StatePublished - May 20 2011


  • Adaptive design
  • Clinical trial
  • Group sequential test
  • Group sequential trial
  • Statistical efficiency
  • Survival analysis


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