Using a single noninferiority margin or preserved fraction for an entire pharmacological class was found to be inappropriate.
OBJECTIVE
To assess the impact on noninferiority decisions when using a single margin or single preserved fraction (PF) for all noninferiority trials within a pharmacological class.


STUDY DESIGN AND SETTING
A search in PubMed, EMBASE, and CENTRAL resulted in seven active-controlled statin trials (nine noninferiority 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 noninferiority (in terms of the PF) varies among comparator statins. The use of a single PF was assessed by reanalyzing noninferiority 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 four of nine (44%) different noninferiority conclusions compared with the original analyses.


CONCLUSION
The threshold of demonstrating noninferiority with a single margin or single PF 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 noninferiority.
['Althunian|Turki A|TA|', 'de Boer|Anthonius|A|', 'Groenwold|Rolf H H|RHH|', 'Klungel|Olaf H|OH|']
D003625:Data Collection D003657:Decision Making D004056:Differential Threshold D004358:Drug Therapy D000074099:Equivalence Trials as Topic D006801:Humans D012107:Research Design
Noninferiority Biostatistics Clinical trials Drug regulation Methodology Randomized controlled trials