PhD candidate, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Professor of Pharmacotherapy, Chairman of the Dutch Medicines Evaluation Board, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Dutch Medicines Evaluation Board, Utrecht, The Netherlands.
J Clin Epidemiol. 2018 Dec;104:15-23. doi: 10.1016/j.jclinepi.2018.07.004. Epub 2018 Aug 25.
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.
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.
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.
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.
评估在药理学类别内的所有非劣效性试验中使用单个边缘或单个保留分数（PF）对非劣效性决策的影响。
在 PubMed、EMBASE 和 CENTRAL 中进行搜索，得出了七项他汀类药物活性对照治疗高血脂症的试验（九项非劣效性比较）。通过计算该边缘是否在比较他汀类药物之间的不同 PF 来评估使用单个边缘的影响，这将表明证明非劣效性（就 PF 而言）的阈值在比较他汀类药物之间有所不同。通过为每个比较他汀类药物使用新的边缘（基于单个 PF）重新分析纳入试验中的非劣效性来评估使用单个 PF。
使用单个边缘导致不同比较者（即不同的阈值）的 PF 范围在 81%至 89%之间。与原始分析相比，使用单个 PF 导致九个中的四个（44%）非劣效性结论不同。
在每个药理学类别中使用单个边缘或单个 PF 来证明效果的非劣效性的阈值可能与为每个比较者分别使用边缘/PF 不一致，并且可能会影响非劣效性的结论。
