Noninferiority Margin Size and Acceptance of Trial Results: Contingent Valuation Survey of Clinician Preferences for Noninferior Mortality

Objectives We used modified contingent valuation methodology to determine how noninferiority margin sizes influence clinicians’ willingness to accept clinical trial results that compare mortality in critically ill children. Methods We surveyed pediatric infectious diseases and critical care clinicians in Canada, Australia, and New Zealand and randomized respondents to review 1 of 9 mock abstracts describing a noninferiority trial of bacteremic critically ill children assigned to 7 or 14 d of antibiotics. Each scenario showed higher mortality in the 7-d group but met noninferiority criterion. We explored how noninferiority margins and baseline mortality rates influenced respondent acceptance of results. Results There were 106 survey respondents: 65 (61%) critical care clinicians, 28 (26%) infectious diseases physicians, and 13 (12%) pharmacists. When noninferiority margins were 5% and 10%, 73% (24/33) and 79% (27/33) respondents would accept shorter treatment, compared with 44% (17/39) when the margin was 20% ( P = 0.003). Logistic regression adjusted for baseline mortality showed 5% and 10% noninferiority margins were more likely to be associated with acceptance of shorter treatment compared with 20% margins (odds ratio [OR] 3.5, 95% confidence interval [CI]: 1.3–9.6, P = 0.013; OR 5.1, 95% CI: 1.8–14.6, P = 0.002). Baseline mortality was not a significant predictor of acceptance of shorter treatment. Conclusions Clinicians are more likely to accept shorter treatment when noninferiority margins are ≤10%. However, nearly half of respondents who reviewed abstracts with 20% margins were still willing to accept shorter treatment. This is a novel application of contingent valuation methodology to elicit acceptance of research results among end users of the medical literature. Highlights Clinicians are more likely to accept shorter treatment durations based on noninferior mortality results when the noninferiority margin is 5% or 10% than if the margin is 20%. However, nearly half of clinicians would still accept shorter-duration treatment as noninferior with margins of 20%. Baseline mortality does not independently predict acceptance of shorter-duration treatment. Contingent valuation is a novel approach to elicit the acceptance of research design parameters from the perspective of endusers of the medical literature.