Using indirect evidence to determine the comparative effectiveness of prescription drugs: do benefits outweigh risks?

Health care decision-makers rarely have the appropriate evidence to evaluate the comparative clinical effectiveness of new and existing prescription drugs. In the absence of head-to-head trials comparing all available drugs, indirect comparisons of randomized trials can offer a valuable approach to investigators evaluating the comparative effect of multiple drugs. Indirect comparisons, particularly methods that allow the combination of direct and indirect evidence obtained from randomized trials, can assist in identifying which of multiple prescription drugs works better than others. In this article, we discuss the benefits and risks of using indirect evidence and make the case in favor of its wider use within the comparative effectiveness research efforts in the US. We further argue that the use of indirect comparisons should be pursued in cases where trials comparing the interventions of interest are available.