Medication Adherence Measurement in Southeast Europe: A Comparative Analysis of Assessment Methods, Digital Health Implementation, and Regulatory Frameworks

Medication adherence is a critical determinant of treatment effectiveness; however, its measurement and integration into routine healthcare practice remain challenging in many healthcare systems. This study aimed to compare medication adherence measurement methods and examine the legal and regulatory frameworks governing adherence-related tools in North Macedonia, Romania, Serbia, and Bulgaria. A structured comparative, two-phase document review was conducted between January and April 2026. The first phase identified and compared medication adherence measurement methods reported in research and recognized within national healthcare systems. The second phase analyzed legislation, regulatory documents, and policy frameworks relevant to adherence-related tools, including digital technologies. Searches were performed in PubMed, Scopus, and Web of Science, together with official governmental, regulatory, and institutional websites. The final evidence base comprised 84 documents, including scientific publications, official legal and policy documents, and regulatory and institutional sources. Across North Macedonia, Romania, and Bulgaria, medication adherence monitoring was not systematically integrated into routine clinical practice, despite differences in digital health infrastructure and regulatory maturity. Traditional indirect methods, particularly prescription refill data and clinician assessment, were more consistently reported, whereas validated direct and digital adherence measurement approaches remained unevenly implemented. Regulatory frameworks differed substantially in scope, specificity, and formal recognition of adherence-related tools, reflecting varying levels of alignment with European digital health policies and contributing to fragmented implementation across healthcare systems. Although existing digital health infrastructure provides a foundation for systematic medication adherence monitoring, implementation remains fragmented because of limited interoperability, inconsistent regulatory support, and the absence of standardized national approaches. Strengthening regulatory guidance, harmonizing adherence measurement standards, integrating adherence indicators into routine healthcare information systems, and formally supporting pharmacist-led adherence services could support more consistent medication adherence monitoring and improve medication management across the healthcare systems of the four analyzed countries.