Lessons learned from conducting a randomized controlled trial to improve non-adherence to antihypertensive drug treatment.

Purpose: Hypertension significantly contributes to cardiovascular diseases and premature deaths. Effective treatment is crucial to reduce cardiovascular risks, but poor adherence to antihypertensive drugs is a major issue. Numerous studies attempted to investigate interventions for identifying non-adherence, but often failed to address the issue effectively. The RHYME-RCT trial sought to bridge this gap by measuring non-adherence by determining antihypertensive drug concentrations in blood through a dried blood spot (DBS) method in patients with resistant hypertension. This measurement was followed by personalized feedback to improve adherence. During the course of this trial several challenges emerged, including selection bias, the gatekeeper role of physicians, the Hawthorne effect and the role of randomization.

Aim: This communication aims to inform fellow researchers and clinicians of challenges that can arise when conducting clinical trials to improve adherence and offer insights for refining study designs to avoid these issues in forthcoming adherence studies.