• Michael Tsui, Sunita Rehal, Vipul Jairath, and Brennan C Kahan.
• Schulich School of Medicine and Dentistry, 1151 Richmond St, London, Ontario N6A 5C1, Canada.
• J Clin Epidemiol. 2019 Jun 1; 110: 82-89.

ObjectivesTo evaluate whether noninferiority trials are designed to adequately preserve the historical treatment effect of their active comparators.Study Design And SettingWe reviewed 162 noninferiority trials published in high-impact medical journals. We assessed whether trials were designed to ensure that interventions could only be declared noninferior if they preserved at least 50% of the active comparator's historical treatment effect.ResultsOnly 25 of 162 trials (15%) were designed so that interventions could only be declared noninferior if they preserved at least 50% of the active comparator's historical treatment effect. Most trials did not provide evidence that the active comparator was effective (n = 101), provided inadequate evidence (n = 18), or used a noninferiority margin that was too wide (n = 18). In a subset of 61 noninferiority trials which referenced a prior randomized trial or meta-analysis evaluating the active comparator, only 25 (41%) used a noninferiority margin small enough to preserve at least 50% of the active comparator's treatment effect. Overall, 14 of 162 noninferiority trials (9%) would have allowed the intervention to be declared noninferior even if it was worse than either placebo or another historical control.ConclusionMost noninferiority trials published in major medical journals could allow erroneous declarations of noninferiority.Copyright © 2019 Elsevier Inc. All rights reserved.

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