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The New England Journal of Statistics in Data Science


Non-inferiority Clinical Trials: Treating Margin as Missing Information
Volume 2, Issue 1 (2024), pp. 104–111
Pub. online: 1 February 2024      Type: Methodology Article      Open accessOpen Access
Area: Cancer Research
Accepted
2 January 2024
Published
1 February 2024

Abstract

Non-inferiority (NI) clinical trials’ goal is to demonstrate that a new treatment is not worse than a standard of care by a certain amount called margin. The choice of non-inferiority margin is not straightforward as it depends on historical data, and clinical experts’ opinion. Knowing the “true”, objective clinical margin would be helpful for design and analysis of non-inferiority trials, but it is not possible in practice. We propose to treat non-inferiority margin as missing information. In order to recover an objective margin, we believe it is essential to conduct a survey among a group of representative clinical experts. We introduce a novel framework, where data obtained from a survey are combined with NI trial data, so that both an estimated clinically acceptable margin and its uncertainty are accounted for when claiming non-inferiority. Through simulations, we compare several methods for implementing this framework. We believe the proposed framework would lead to better informed decisions regarding new potentially non-inferior treatments and could help resolve current practical issues related to the choice of the margin.

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© 2024 New England Statistical Society
Open access article under the CC BY license.

Keywords
Incomplete data Margin justification Multiple imputation Non-inferiority Survey

Funding
This project was partially supported by Award Number DMS-2015320 from the National Science Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Science Foundation.

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