Group sequential designs for monitoring survival probabilities

Biometrics. 1996 Sep;52(3):1033-41.


In the present paper we derive the asymptotic joint distribution of the Nelson-Aalen estimators for the cumulative hazard function (or the Kaplan-Meier estimators for the survival function) calculated at different (possibly random) calendar time points of a survival study. This result is used to develop group sequential designs for clinical trials in which patients are enrolled over an extended period and the survival probability at a given failure time point is the parameter of primary interest. The proposed designs allow monitoring the survival probability (or probabilities) at interim looks so that the study can be terminated when there is sufficient evidence for a positive or negative result. A detailed illustration is provided with a problem from the National Wilms Tumor Study Group, which motivated this research.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Biometry
  • Child
  • Child, Preschool
  • Clinical Protocols
  • Clinical Trials as Topic / statistics & numerical data*
  • Combined Modality Therapy
  • Data Interpretation, Statistical
  • Humans
  • Infant
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / surgery
  • Probability
  • Survival Analysis*
  • Wilms Tumor / drug therapy
  • Wilms Tumor / mortality
  • Wilms Tumor / surgery