An Empirical Analysis of Noninferiority Studies in Oncology: Are They Good Enough?

Authors: Alyson Haslam PhDa, Jennifer Gill MSa, and Vinay Prasad MD, MPHb,c,d,e
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  • a Knight Cancer Institute,
  • | b Division of Hematology Oncology, Knight Cancer Institute,
  • | c Department of Public Health and Preventive Medicine,
  • | d Center for Health Care Ethics, and
  • | e Division of General Medicine, Department of Medicine, Oregon Health & Science University, Portland, Oregon.
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Background: Noninferiority (NI) trials should help identify interventions that offer some benefit (eg, lower financial costs, more tolerable, or less invasive) without sacrificing noticeable effectiveness, and researchers should adhere to appropriate standards in the conduct and reporting of methods. This study describes the characteristics of a systematic sampling of NI studies from an updated search of recent published oncology trials. Methods: We performed a cross-sectional analysis of NI research published between 2014 and 2018 in the top 3 medical journals and top 3 oncology journals. We estimated the percentage of NI trials in oncology that report informative details of study, such as justification for conducting NI trial, justification of NI margin, analysis population, and alpha level. Results: There were 94 NI studies and 104 comparisons, and 59.6% (n=62) of comparisons declared NI. The median NI margin of comparisons reporting an odds or hazard ratio was 1.3 (1.05–3.2; n=64). Twenty-three percent (n=22) of studies did not provide a justification for conducting a NI study; 54.3% (n=51) of studies did not provide a justification of the margin they used in their study. Only approximately 46% (n=43) of comparisons used both an intention-to-treat (ITT) and per-protocol (PP) analysis, and 37.3% (n=35) of studies used a one-sided alpha level of >.025. There is notable variation in key elements of the conduct and reporting of NI trials, including the NI margin, the alpha level, and the population analyzed. Furthermore, a high number of studies do not provide justification for conducting a NI study or the margin used for determining NI. Conclusions: These results suggest that there is room for improvement in the reporting and conduct of NI trials in oncology.

Submitted July 5, 2019; accepted for publication August 27, 2019

Author contributions: Study concept: Haslam, Prasad. Data acquisition and analysis: Haslam, Gill. Manuscript preparation: All authors.

Disclosures: Dr. Prasad has disclosed that he receives royalties from his book Ending Medical Reversal; his work is funded by the Laura and John Arnold Foundation; he has received honoraria for grand rounds/lectures from several universities, medical centers, and professional societies, and payments for contributions to Medscape; and he hosts the podcast “Plenary Session,” which has Patreon backers. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Correspondence: Alyson Haslam, PhD, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239. Email:

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