Department of Orthopaedic Surgery, MedStar Union Memorial Hospital, Baltimore, MD, USA.
Foot Ankle Int. 2022 Oct;43(10):1364-1369. doi: 10.1177/10711007221112928. Epub 2022 Aug 18.
Subjective assumptions on the definition of surgical success are inherent to the design of clinical trials with a categorial outcome. The current study used reasonable alternative assumptions about surgical care to reassess data for the randomized controlled Cartiva trial (MOTION).
Data from the published study were augmented by publicly accessible internal US Food and Drug Administration documents. As in the published report, 1-sided lower bound 95% CIs (LBCI95) for the difference of proportions were calculated for a series of alternative scenarios in which the assumptions underlying what constitutes surgical success were altered.
Using a noninferiority margin of -15%, the MOTION trial reported success based on a 1-sided LBCI95 of -10.9%. Each of the 3 independent alternative scenarios analyzed yielded results that altered the primary outcome of the trial: (1) eliminating failures based solely upon radiographs findings, thereby considering a painless pseudarthrosis as a success (1-sided LBCI95 of -15.9%), (2) considering only major surgical revision as a failure and discounting isolated hardware removal (1-sided LBCI95 of -15.1%), and (3) using a visual analog scale (VAS) pain threshold of <30 as the success criterion rather than a 30% reduction in VAS pain score (1-sided LBCI95 of -15.8%).
In this reanalysis, applying any of 3 reasonable alternative assumptions about the definition of surgical success to the data resulted in failure to prove noninferiority of Cartiva over arthrodesis, a reversal of the reported trial result. These results highlight the effect of subjective assumptions in the design of clinical trials with a categorical outcome and illustrate how differing philosophies about what constitutes surgical success can be pivotal in determining the final result.
Level II, prospective comparative study.
在具有类别结果的临床试验设计中，对手术成功的定义的主观假设是固有存在的。本研究使用了对手术护理的合理替代假设，重新评估了随机对照 Cartiva 试验（MOTION）的数据。
在已发表研究的数据基础上，增加了可公开获取的美国食品和药物管理局内部文件。与已发表报告一样，计算了一系列替代方案的单侧下限 95%置信区间（LBCI95），这些方案改变了构成手术成功的假设。
使用非劣效性边界 -15%，MOTION 试验根据单侧 LBCI95 为 -10.9%报告成功。分析的 3 个独立替代方案中的每一个都得出了改变试验主要结果的结果：（1）仅根据 X 光片结果排除失败，从而将无痛假关节视为成功（单侧 LBCI95 为 -15.9%），（2）仅将主要手术修正视为失败，并忽略单独的硬件移除（单侧 LBCI95 为 -15.1%），以及（3）将视觉模拟量表（VAS）疼痛阈值 <30 作为成功标准，而不是 VAS 疼痛评分降低 30%（单侧 LBCI95 为 -15.8%）。
在这项重新分析中，将手术成功定义的 3 种合理替代假设中的任何一种应用于数据，都无法证明 Cartiva 不劣于融合，这与报告的试验结果相反。这些结果突出了主观假设在具有类别结果的临床试验设计中的影响，并说明了什么构成手术成功的不同理念如何在确定最终结果方面发挥关键作用。
二级，前瞻性比较研究。
