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

Points• Adherence to prescribed treatment remains a critical component of clinical trials in tuberculosis (TB) treatment.Recent evidence indicates that adherence strongly influences the outcome of therapy; attention to its quantification and measures to assure its implementation should increase.• In the context of a World Health Organization (WHO) Technical Consultation on "Advances in Clinical Trial Design for Development of New TB Treatments," we reviewed the challenges related to adherence confronting the trials community.• We discuss the importance of adherence to therapy in TB clinical trials, consider several definitions and measures of adherence, comment on the standard provided by directly observed therapy (DOT), and briefly review evolving electronic methods for the assessment of adherence.• Adherence affects both the outcome of therapy and the risk of acquired drug resistance.Assessment of adherence should consider not only overall adherence but also the timing and intensity of nonadherence.• Appropriate methods for pooling and analyzing electronic data on adherence are needed.• Better methods are needed for linking information on adherence to individual pharmacokinetics and pharmacodynamics and to individual patient outcomes.