Effect on Treatment Adherence of Distributing Essential Medicines at No Charge: The CLEAN Meds Randomized Clinical Trial

Abstract

Importance: Nonadherence to treatment with medicines is common globally, even for life-saving treatments. Cost is one important barrier to access, and only some jurisdictions provide medicines at no charge to patients.

Objective: To determine whether providing essential medicines at no charge to outpatients who reported not being able to afford medicines improves adherence.

Design, setting, and participants: A multicenter, unblinded, parallel, 2-group, superiority, outcomes assessor-blinded, individually randomized clinical trial conducted at 9 primary care sites in Ontario, Canada, enrolled 786 patients between June 1, 2016, and April 28, 2017, who reported cost-related nonadherence. Follow-up occurred at 12 months. The primary analysis was performed using an intention-to-treat principle.

Interventions: Patients were randomly allocated to receive free medicines on a list of essential medicines in addition to otherwise usual care (n = 395) or usual medicine access and usual care (n = 391).

Main outcomes and measures: The primary outcome was adherence to treatment with all medicines that were appropriately prescribed for 1 year. Secondary outcomes were hemoglobin A1c level, blood pressure, and low-density lipoprotein cholesterol levels 1 year after randomization in participants taking corresponding medicines.

Results: Among the 786 participants analyzed (439 women and 347 men; mean [SD] age, 51.7 [14.3] years), 764 completed the trial. Adherence to treatment with all medicines was higher in those randomized to receive free distribution (151 of 395 [38.2%]) compared with usual access (104 of 391 [26.6%]; difference, 11.6%; 95% CI, 4.9%-18.4%). Control of type 1 and 2 diabetes was not significantly improved by free distribution (hemoglobin A1c, -0.38%; 95% CI, -0.76% to 0.00%), systolic blood pressure was reduced (-7.2 mm Hg; 95% CI, -11.7 to -2.8 mm Hg), and low-density lipoprotein cholesterol levels were not affected (-2.3 mg/dL; 95% CI, -14.7 to 10.0 mg/dL).

Conclusions and relevance: The distribution of essential medicines at no charge for 1 year increased adherence to treatment with medicines and improved some, but not other, disease-specific surrogate health outcomes. These findings could help inform changes to medicine access policies such as publicly funding essential medicines.

Trial registration: ClinicalTrials.gov identifier: NCT02744963.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Persaud reported receiving grants from Canadian Institutes for Health Research (CIHR) and Ontario SPOR Support Unit during the conduct of the study; receiving salary support from the Canada Research Chairs Program, Physicians Services Incorporated Foundation, Department of Family and Community Medicine at St Michael’s Hospital, and the University of Toronto Department of Family and Community Medicine; and receiving nonfinancial support from Public Health Agency of Canada outside the submitted work. Dr Glazier reported receiving grants from CIHR, Ontario SPOR Support Unit, and St Michael’s Hospital Foundation during the conduct of the study; receiving personal fees from ICES (Institute for Clinical Evaluative Sciences), St Michael’s Hospital, and University of Toronto outside the submitted work; and receiving a portion of income paid by CIHR to ICES to support the role of Scientific Director of the CIHR Institute of Health Services and Policy Research. Dr Gomes reported receiving grants from Ontario Ministry of Health and Long-Term Care outside the submitted work. Dr Jüni reported receiving grants from CIHR, AstraZeneca, Biotronik, Biosensors International, Eli Lilly, The Medicines Company, and Ontario SPOR Support Unit outside the submitted work; and serving as an unpaid member of the steering group of trials funded by AstraZeneca, Biotronik, Biosensors, St Jude Medical, and The Medicines Company. Dr Law reported receiving personal fees from Health Canada, Hospital Employees’ Union, Attorney General of Canada, and Conference Board of Canada outside the submitted work. Dr Mamdani reported receiving personal fees from NovoNordisk, Allergan, and Amgen outside the submitted work. Dr Martin reported serving as Executive Vice President and Chief Medical Executive, Women’s College Hospital. Dr Oh reported receiving fees for advisory board membership from Amgen, AstraZeneca, and Bayer outside the submitted work. Dr Pinto reported being supported as a Clinician Scientist by the Department of Family and Community Medicine, Faculty of Medicine, University of Toronto, the Department of Family and Community Medicine, St Michael’s Hospital, and the Li Ka Shing Knowledge Institute, St Michael’s Hospital; being supported by a fellowship from the Physicians’ Services Incorporated Foundation and as the Associate Director for Clinical Research at the University of Toronto Practice-Based Research Network (UTOPIAN); and receiving honoraria for presentations at Queen’s University (2010), University of Saskatchewan (2012), Mount Sinai Hospital (2012), Toronto Reference Library (2016), Law Society of Ontario (2016), Japan Network of Health Promoting Hospitals & Health Services (2018), and the Joint Centre for Bioethics, University of Toronto (2019). Mr Umali reported receiving grants from St Michael’s Hospital Foundation and Ontario SPOR Support Unit; and receiving fees from St Michael’s Hospital during the conduct of the study. Dr Tu reported receiving grants from Ontario SPOR Support Unit during the conduct of the study. Dr Laupacis reported receiving honoraria for serving on clinical trial data monitoring committees from Novartis outside the submitted work. No other disclosures were reported.

Figures

Figure.. Participant Flow Diagram