Early clinical trial termination: simulation-based design of a robust stopping rule using difference in interventional effect on mortality

Yeong Shiong Chiew, Geoffrey M. Shaw, Paul Docherty, Jennifer Dickson, Christopher Pretty, J. Geoffrey Chase

    Research output: Chapter in Book/Report/Conference proceedingConference PaperOther


    Stopping rules are established for early clinical trial termination based on a statistically apparent treatment efficacy as part of a randomised controlled trial (RCT) interim analysis. Well-designed stopping rules are required to prevent participants from ongoing use of a treatment found inferior or even harmful, or potentially to stop a trial early if sufficient evidence of a superior outcome has been obtained. In this study, a stopping rule based on observing an inferior mortality rate of a two-Arm RCT is developed. The stopping rule is developed using a Monte Carlo simulation approach, informed by previously collected data. This simulation based method can be adapted for any two-Arm randomised controlled trial that monitors binary outcomes. Practical case examples of how the stopping rule can be implemented are presented and the stopping rule is also validated against retrospective data. This simulation based approach in designing a RCT stopping rule can be adjusted to the participating cohort based on the desired study characteristics, and fulfils ethical needs for a statistically justifiable stopping rule.

    Original languageEnglish
    Title of host publicationIECBES 2016 - IEEE-EMBS Conference on Biomedical Engineering and Sciences
    PublisherIEEE, Institute of Electrical and Electronics Engineers
    Number of pages6
    ISBN (Electronic)9781467377911
    Publication statusPublished - 2016
    EventIEEE-EMBS International Conference on Biomedical Engineering and Sciences (IECBES) 2016 - Kuala Lumpur, Malaysia
    Duration: 4 Dec 20168 Dec 2016
    https://ieeexplore.ieee.org/xpl/conhome/7829191/proceeding (Proceedings)


    ConferenceIEEE-EMBS International Conference on Biomedical Engineering and Sciences (IECBES) 2016
    Abbreviated titleIECBES 2016
    CityKuala Lumpur
    Internet address


    • Monte-Carlo simulation
    • randomised controlled trial
    • stopping rule

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