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Editorial
. 2025 May;4(5):101715.
doi: 10.1016/j.jacadv.2025.101715. Epub 2025 Apr 25.

Rethinking Noninferiority

Bjorn Redfors  1
Affiliations
Editorial

Rethinking Noninferiority

Bjorn Redfors. JACC Adv. 2025 May.
No abstract available

Keywords: Bayesian statistics; noninferiority; randomized controlled trials.

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Conflict of interest statement

Funding support and author disclosures The author has reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Proposed Stepwise Approach to Definitive Approval of New Therapies Introduced Via Noninferiority Trials (Left) In the initial study cohort, a preliminary noninferiority assessment is conducted using a permissive NI margin (A), for example, requiring at least 95% probability that the true effect falls within this margin. Meeting this threshold grants conditional approval, with continued trials assessing a stricter NI margin (B) within a set time frame. Since the therapy is already on the market, the financial burden is lower than requiring a stringent margin upfront. If it fails step B, it is withdrawn; if successful, it must ultimately meet a clinically insignificant NI margin for full approval. (Right) Alternatively, a strict NI margin could be set from the start, with lower probability requirements for initial versus definitive approval. The right panel shows more probability mass extending beyond the NI margin at the initial stage (A) than at the definitive stage (C). NI = noninferiority; PDF = probability density function; TE = treatment effect.
See this image and copyright information in PMC

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