Philosophies of Surgical Care Are Embedded in Outcome Studies: An Illustrative Reanalysis of the Cartiva MOTION Trial.

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.