The Restricted Mean Survival Time as a Tool for Ranking Comparative Outcomes in a Narrative Review that Evaluates a Network of Randomized Trials: An Example Based on PCSK9 Inhibitors.

INTRODUCTION

On the basis of two randomized trials, evolocumab and alirocumab have been approved in patients with cardiovascular disease. The evidence on these two agents has been studied through different methods of analysis that span from narrative approaches to network meta-analysis. In the present study, we assessed the performance of a narrative approach combined with the application of the restricted mean survival time (RMST).

METHODS

We studied the two pivotal placebo-controlled trials focused on evolocumab and alirocumab. Our original framework of comparative assessment employed the RMST. Our objective was to show that in the context of a narrative review, the RMST can be an efficient although simple tool to make indirect comparisons. The endpoint was event-free survival, expressed in months.

RESULTS

For each cohort of patients (13,784 patients administered evolocumab, 9462 patients administered alirocumab, 23,242 controls), we determined the RMST values with 95% confidence intervals (CI) [evolocumab: 33.60 months, 95% CI 33.46-33.74; alirocumab: 34.07 months, 95% CI 33.92-34.22]. These results, along with those of the control groups, were analyzed and interpreted narratively. Univariate statistics were conducted, but no network meta-analysis was performed.

CONCLUSION

The experience presented herein indicates that a framework of evidence assessment focused on the RMST is a worthwhile option. Our study is in line with the growing literature that has recently emphasized the methodological advantages of the RMST.