Medication adherence: An overlooked critical determinant of pharmacological effectiveness.

Medication adherence and therapeutic inertia are 2 major barriers to the optimal control of chronic diseases in clinical practice. In drug development, these factors contribute to variability in drug exposure and may substantially influence estimates of efficacy, safety, and benefit-risk balance, but they frequently remain overlooked. Medication adherence is a complex and dynamic process characterized by several patterns and a large number of determinants that may exert variable, phase-specific, and time-dependent effects throughout the medication-taking process. A major challenge remains the accurate monitoring of drug adherence, the ideal goal being that of obtaining a reliable dosing history and confirmation that the medication has been taken as prescribed. Several new approaches discussed in this review are available to monitor adherence in clinical studies with more precision, but their implementation remains limited. This review discusses contemporary approaches to improve patients' medication adherence and to limit physicians' inertia, another form of poor adherence. Among them, interprofessional collaborations have demonstrated sustained improvements in adherence and therapeutic inertia. However, this approach still needs profound changes in terms of interprofessional education and collaboration and strong support from teaching organizations and health care providers. Finally, our review addresses an often overlooked issue in drug development, eg, the need to consider the entire drug life cycle from chemical development to the accumulation and disposal of drugs when unused. Medication nonadherence is now recognized as a significant driver of pharmaceutical waste and environmental burden. Modern clinical pharmacology should consider the global environmental impact of drugs. SIGNIFICANCE STATEMENT: Medication adherence and therapeutic inertia are 2 major determinants of variable drug exposure but they remain insufficiently recognized and systematically addressed. This review examines the taxonomy, the multiple determinants of nonadherence and therapeutic inertia, the various methods available to measure adherence, and some innovative approaches for designing future clinical trials that account for these 2 variables. Finally, we address an increasingly important but often overlooked consequence of poor medication adherence: the environmental and economic impact of unused medicines.