Medication Adherence Measurement Methods in Registration Trials Supporting the Approval of New Medicines: A Cross-Sectional Analysis of Centralized Procedures in the European Union 2010–2020

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Medication adherence is a key factor impacting efficacy and safety of medicines, yet how it is dealt with in European registration trials is unknown. A cross-sectional analysis of European Medicines Agency (EMA) marketing authorization dossiers for new medicines approved through centralized procedures in the European Union between 2010 and 2020 was performed. Data were extracted from European Public Assessment Reports and Clinical Study Reports. Clinical trials covering five therapeutic areas were included: diabetes, respiratory conditions, cardiovascular diseases, infectious diseases, and oncology. Outcomes included adherence assessment, measurement methods, and rates. Overall, 102 medicines studied in 253 clinical trials were reviewed. All but one study reported measuring adherence. Two hundred twenty trials (87%) measured adherence using quantitative methods, while 32 (13%) trials monitored adherence but did not further quantify. Reported adherence rates were high (> 90%) across trials yet marked disparities in measurement methods and definitions were found. The most frequently used adherence measurement method was pill/dose count (single method: 52.7%; in combination: 37.7%; with patient diary/report: 17.3%; electronic methods: 1.4%; bioanalytical methods: 4.1%). Patient diary/report (6.4%) and electronic methods (2.7%) were also used as single methods. Electronic methods were more often used in respiratory and anti-infective trials, while bioanalytical methods were more frequently used in diabetes. Overall, adherence is measured in EMA registration trials, yet the methods used and the way in which adherence rates are presented vary widely between trials and therapeutic areas. To better understand and compare efficacy of medicines, standardization of adherence definitions and measurement methods is needed.

Original languageEnglish
JournalClinical Pharmacology and Therapeutics
Issue number5
Pages (from-to)1051-1060
Publication statusPublished - 2022

Bibliographical note

Funding Information:
The work was supported by a Short‐Term Scientific Mission (STSM) grant from COST Action CA19132 “ENABLE,” supported by COST (European Cooperation in Science and Technology).

Funding Information:
The institute of Job van Boven (J.F.M.v.B.), i.e., the Medication Adherence Expertise Center of the Northern Netherlands (MAECON) based at the University Medical Center Groningen, has received funding from various companies to study medication adherence management tools. Christine Erikstrup Hallgreen (C.E.H.) is employed by the University of Copenhagen at the Copenhagen Centre for Regulatory Science (CORS). CORS is a cross‐faculty university anchored institution involving various public (Danish Medicines Agency, Copenhagen University) and private stakeholders (Novo Nordisk, Lundbeck, Ferring pharmaceuticals, LEO pharma) as well as patient organizations (Rare Diseases Denmark). The centre is purely devoted to the scientific aspects of the regulatory field and with a patient‐oriented focus, and the research is not company‐specific product or directly company related. Katerina Maria Mantila (K.M.M.) was during the study period, from February 2021 to August 2021, a master's thesis student at the University of Copenhagen at the CORS, with an internship at the Dutch Medicines Evaluation Board (CBG‐MEB)/University of Medical Centre Groningen (UMCG). Since February 2022, K.M.M. has been working at PharmaLex. PharmaLex was not involved in any aspects of this study. All other authors declared no competing interests for this work.

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