Accepted for/Published in: JMIR Research Protocols
Date Submitted: May 6, 2025
Open Peer Review Period: May 6, 2025 - Jul 1, 2025
Date Accepted: Dec 8, 2025
(closed for review but you can still tweet)
Methods of Analysis in Randomised Non-Inferiority Trials: A Methodological Survey Protocol
ABSTRACT
Background:
Non-inferiority (NI) trial designs that investigate whether an experimental intervention is no worse than standard of care have been used increasingly in recent years. The robustness of the conclusions are in part dependent on the analysis population set used for the analysis. In the NI setting, the intention-to-treat (ITT) and per-protocol (PP) analysis sets are most common. The ITT analysis has been thought to be anti-conservative compared to the PP analysis.
Objective:
To conduct a methodological review assessing the analysis population sets used in contemporary NI trials.
Methods:
A comprehensive electronic search strategy will be used to identify studies indexed in Medline, Embase, Emcare, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Studies will be included if they are non-inferiority trials published in 2024. The primary outcome is the analysis population used in the primary analysis of the trial (ITT, PP, or AT). Secondary outcomes will include the NI margin, effect estimates, point estimates, and corresponding confidence intervals of the analysis. Analysis will be done using descriptive statistics.
Results:
Originally, 1209 studies were captured in the comprehensive search. 403 trials were eligible for extraction. Extraction started in January 2025 and will be completed in January 2026.
Conclusions:
This methodological survey of NI trials will describe the population analysis set used in primary analysis and assess factors which could be associated with each analysis method.
Citation
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Copyright
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