The importance of adherence in tuberculosis treatment clinical trials and its relevance in explanatory and pragmatic trials

Abstract

In conclusion, medication adherence remains a critical, yet understudied, factor influencing outcomes of TB therapy. Its importance has been recognized since the advent of effective antituberculosis therapy, and the vital role adherence plays in the conduct of TB clinical trials has been further highlighted in contemporary clinical trials [11]. The growing importance of noninferiority trial designs and the challenge of interpreting PP analyses have focused more attention on the issue of precisely measuring adherence and adherence patterns. Adherence is important in both superiority and noninferiority trials and in both intent-to-treat (ITT) and per-protocol (PP) analyses; both should be performed, and both should assess the impact of variation in adherence. Only recently has our ability to measure adherence improved. Novel (in particular, electronic) methods for assessing and encouraging adherence hold promise, and efforts to develop a robust evidence base to support them are growing. Our understanding of the impact of nonadherence on key outcomes (treatment success, emergence of resistance) in TB treatment trials is relatively modest but is also receiving increased attention from investigators. Continued development of more convenient, more reliable, and less costly means to achieve high levels of adherence will serve both trials and programs well.