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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)

The final, peer-reviewed published version of this preprint can be found here:

Methods of Analysis in Randomized Noninferiority Trials: Methodological Survey Review Protocol

Xie D, McKechnie T, Staibano P, Arvikar E, Gou D, Longia S, Maatallah A, Maatallah M, Wang B, Wang Y, Parpia S

Methods of Analysis in Randomized Noninferiority Trials: Methodological Survey Review Protocol

JMIR Res Protoc 2026;15:e76876

DOI: 10.2196/76876

PMID: 41824746

Warning: This is an author submission that is not peer-reviewed or edited. Preprints - unless they show as "accepted" - should not be relied on to guide clinical practice or health-related behavior and should not be reported in news media as established information.

Methods of Analysis in Randomised Non-Inferiority Trials: A Methodological Survey Protocol

  • Daniel Xie; 
  • Tyler McKechnie; 
  • Phillip Staibano; 
  • Eisha Arvikar; 
  • David Gou; 
  • Shyreen Longia; 
  • Ali Maatallah; 
  • Mohamed Maatallah; 
  • Borong Wang; 
  • Yang Wang; 
  • Sameer Parpia

ABSTRACT

Introduction: 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. The intention-to-treat (ITT) analysis has been thought to be anti-conservative compared with the per-protocol (PP) analysis in the NI setting. Methods and analysis: We aim to conduct a methodological review assessing the analysis population set used in NI trials. 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 or PP). Secondary outcomes will be the NI margin, effect estimates, point estimates, and corresponding confidence intervals of the analysis. Analysis will be done using descriptive statistics. Discussion: 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


 Citation

Please cite as:

Xie D, McKechnie T, Staibano P, Arvikar E, Gou D, Longia S, Maatallah A, Maatallah M, Wang B, Wang Y, Parpia S

Methods of Analysis in Randomized Noninferiority Trials: Methodological Survey Review Protocol

JMIR Res Protoc 2026;15:e76876

DOI: 10.2196/76876

PMID: 41824746

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