Unified exact design with early stopping rules for single arm clinical trials with multiple endpoints

Stat Methods Med Res. 2021 Jul;30(7):1575-1588. doi: 10.1177/09622802211013062. Epub 2021 Jun 23.

Abstract

Adaptive designs are gaining popularity in early phase clinical trials because they enable investigators to change the course of a study in response to accumulating data. We propose a novel design to simultaneously monitor several endpoints. These include efficacy, futility, toxicity and other outcomes in early phase, single-arm studies. We construct a recursive relationship to compute the exact probabilities of stopping for any combination of endpoints without the need for simulation, given pre-specified decision rules. The proposed design is flexible in the number and timing of interim analyses. A R Shiny app with user-friendly web interface has been created to facilitate the implementation of the proposed design.

Keywords: Go/no go decisions; biomarker endpoints; conditional power; early phase; multiple endpoints.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computer Simulation
  • Medical Futility*
  • Probability
  • Research Design*