Background:
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).
Methods:
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.
Results:
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%).
Conclusion:
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 of Evidence:
Level II, prospective comparative study.
