SAS macros for group sequential designs for survival endpoint with non-proportional hazards

Oregon Convention Center 

Group sequential designs (GSD) allow sequential monitoring of efficacy and safety as part of interim testing in clinical trials. Although literature is well developed for GSD with continuous and binary endpoints, options are restrictive when dealing with time-to-event endpoints. Commercial software provides options for executing GSD only using the proportional hazards or with assumption of exponentially distributed survival time. We have developed a novel simulation-based GSD for the non-proportional hazards scenario utilizing the concept of Relative Time. We present two new SAS macros that can execute such GSDs – {i} with both efficacy and futility boundaries, {ii} with efficacy only boundary. Our SAS macros provide many advanced features – binding/non-binding futility rules, skipping for futility, flexible error spending, equal/non-equal spaced interim looks, and allow administrative censoring and dropouts. A user-friendly output (both numeric and graphic) displays sample size calculation and the efficacy/futility cut-off boundaries. The macros also generate three dimensional plots showing expected reduction in sample size when using GSD compared to usual fixed two-arm trials.

group sequential design

non-proportional hazards

SAS macro

time-to-event endpoint

sample size

Relative Time 

Biometrics Section