Medical Decision Making with Incomplete Evidence—Choosing a Platelet Glycoprotein IIbIIIa Receptor Inhibitor for Percutaneous Coronary Interventions

Abstract

Background. Medical decision making must often be performed despite incomplete evidence. An example is the choice of a glycoprotein IIb/IIIa (GP2b3a) inhibitor, a class of potent antiplatelet medications, as adjunctive therapy during percutaneous coronary interventions (PCIs). GP2b3a inhibitor efficacy in reducing adverse outcomes has been well documented with multiple placebo-controlled randomized trials, but there is a paucity of comparative data about their individual equivalency. Substantial cost differentials are also present between the drugs. Methods. A systematic review of the literature was performed to identify all randomized placebo-controlled trials of GP2b3a inhibitors as adjunctive therapy for PCI. Three complimentary methods were used to assist in decision making regarding drug equivalency. First, the data from the single direct comparative trial are analyzed from a Bayesian perspective. Next, prior information from other GP2b3a inhibitor trials in similar but not identical patient populations is incorporated. In the 3rd method, indirect comparisons of GP2b3a inhibitors are carried out using a hierarchical meta-analytic model of the placebo-controlled trials identified by the systematic review. Results. A total of 12 randomized trials were identified involving 3 agents (abciximab, eptifibatide, tirofiban), but only 1 involved a direct comparison of 2 drugs (abciximab v. tirofiban). In contradiction to the original publication, the authors’ Bayesian analysis both without (method 1) and with (method 2) the inclusion of some prior information suggests a reasonable probability of equivalency. The indirect comparisons from all randomized placebo-controlled trials (method 3) also failed to provide support for superiority of any agent over the others. Conclusion. Decision making with incomplete evidence is a difficult but frequently occurring medical dilemma. The authors propose 3 methods that may elucidate the process and illustrate them in the context of the choice of GP2b3a inhibitor for adjunctive therapy during PCI. Further data may or may not eventually lead to a different conclusion, but based on the evidence available to date, the authors’ 3 methods suggest clinical equivalency between GP2b3a inhibitors, in contrast to the initial conclusions from the single comparative randomized trial.