Using a single non-inferiority margin or preserved fraction for an entire pharmacological class was found to be inappropriate

Abstract

OBJECTIVE: To assess the impact on non-inferiority decisions when using a single margin or single preserved fraction (PF) for all non-inferiority trials within a pharmacological class. STUDY DESIGN AND SETTING: A search in PubMed, EMBASE, and CENTRAL resulted in seven active-controlled statin trials (nine non-inferiority comparisons ) for treating hyperlipidemia. The impact of using a single margin was assessed by calculating whether this margin corresponds to different PFs among comparator statins which will demonstrate that the threshold of demonstrating non-inferiority (in terms of the PF) varies among comparator statins. The use of a single PF was assessed by reanalyzing non-inferiority in the included trials with new margins (based on the single PF) for each comparator statin. RESULTS: The use of a single margin resulted in PFs that range between 81% and 89% for the different comparators (i.e. different thresholds). The use of a single PF resulted in 4 of 9 (44%) different non-inferiority conclusions compared to the original analyses. CONCLUSION: The threshold of demonstrating non-inferiority with a single margin or single preserved fraction of the effect per pharmacological class may not be consistent with using a margin / PF for each comparator separately and may impact the conclusions of non-inferiority.