JAMA Health Forum – Health Policy, Health Care Reform, Health Affairs | JAMA Health Forum

Key Points

Trial Registration 
ClinicalTrials.gov Identifier: NCT02744963

Few interventions have been shown to reduce costs in health care.1 Health inequities associated with avoidable disparities in outcomes based on income, racism, and other forms of discrimination are estimated to contribute substantially to health spending through poor outcomes for disadvantaged individuals. These inequities can be reduced with better access to basic necessities and health care, including preventive care.^2,3 The quintuple aim is to reduce costs, improve outcomes, improve patients’ and clinicians’ experiences, and promote health equity.⁴

Cost-related nonadherence to medicines, defined as not taking medicines as instructed because of the cost, is more prevalent among people with low incomes and is associated with poor health outcomes.5 The CLEAN Meds (Carefully Selected and Easily Accessible at No Charge Medications) trial examined the effects of free distribution of essential medicines among people experiencing cost-related nonadherence in Ontario, Canada, where physician and hospital care services, but not prescription medications, are universally funded by public payers.⁶ Over 24 months, the CLEAN Meds trial demonstrated that free medicine distribution improved medicine adherence and reduced health care costs.⁷ Free medicine distribution had mixed effects on surrogate health outcomes, reducing systolic blood pressure after 12 months⁶ but not substantially reducing hemoglobin A_1c levels, low-density lipoprotein levels, or blood pressure at 24 months.⁷ In this secondary analysis of the CLEAN Meds trial, we report the 36-month results of free medicine distribution on health care costs and health care encounters among primary care patients experiencing cost-related nonadherence.

This was a parallel 2-arm individually randomized clinical trial of patients from 9 primary care sites in Ontario, Canada. After initiation of the trial that was originally planned to last 12 months for each participant, additional funding was obtained to extend the intervention to 36 months, but primary data collection from the control group ended after 24 months.6 During the second year of the trial, we decided to compare prespecified outcomes collected passively using health administrative claims data over 36 months. The full study protocol is presented in Supplement 1. The study was reviewed and approved by the Unity Health Toronto Research Ethics Board. Participants provided written informed consent. This report and previous reports follow the Consolidated Standards of Reporting Trials (CONSORT) reporting guideline and include the use of flow diagrams.⁸

Participants allocated to the free medicine distribution group received free access to 128 essential medicines (listed in the eMethods in Supplement 2).⁹ Medicines were mailed to participants in the free distribution group except for time-sensitive medicines such as antimicrobial agents that were dispensed at the point of care. Controlled substances such as opioid analgesics were not included in the intervention, and these medicines, along with other medicines not on the list of essential medicines, could be accessed through usual methods. Participants randomly allocated to the usual access group generally obtained medicines at a community pharmacy. Usual access included out-of-pocket payments for the full cost of medicines, public insurance for social assistance recipients (including those receiving welfare or disability supports), and private insurance.

Total health care costs were a prespecified secondary outcome of the CLEAN Meds trial, and it is reported as the main focus of this 36-month report. The primary outcome of adherence to appropriately prescribed medicines was previously reported at 12 and 24 months.6^,7 Health care–related costs were considered from the governmental payer’s perspective. Health care costs were determined using administrative data from Ontario’s single-payer health care system to ascertain the following outcomes: (1) costs of ambulatory visits with primary care physicians, (2) costs of ambulatory visits with specialist physicians, and (3) other physician costs, including laboratory testing, emergency department visits, hospitalizations, publicly funded medications, and home care (eg, home visits by nurses, physiotherapists, and occupational therapists). Publicly funded medicines include medicines covered by public drug plans for social assistance recipients, including those receiving welfare or disability and those older than 65 years. All costs are reported in Canadian dollars with adjustments for inflation. Deaths were also ascertained using administrative data as a potential marker of adverse effects.

A total of 1130 patients were assessed for eligibility, and 786 (mean [SD] age, 51 [14] years; 421 [56.4%] female) were randomly allocated between June 1, 2016, and April 28, 2017. Of those randomized, 39 patients (5.0%) did not consent to the use of health care administrative data, including 13 of 395 patients (3.3%) in the free distribution group and 26 of 391 patients (6.6%) in the usual access group (Figure 1); the characteristics of those included were similar to those randomized (Table 1). This analysis compared 382 patients in the free distribution group and 365 patients in the usual access group. There were 8 deaths (2.1%) in the free medicine distribution group and 14 deaths (3.8%) in the usual access group (P = .16).

Eliminating out-of-pocket medication fees was associated with a lower median total health care spending over 3 years of $1641 (95% CI, $454-$2792; P = .006; Table 2). Free distribution was associated with a lower number of participants with very high total health care costs (Figure 2). Hospitalizations represented the largest cost in both groups (Table 2). However, between the free distribution and usual access groups, there was not a statistically significant difference in the number of hospitalizations (mean [SD], 0.9 [1.6] vs 1.2 [3.0]; P = .08) or the rate of being hospitalized at least once (38.7% vs 44.1%; P = .14) (Table 3). There was no statistically significant reduction in primary care visits, specialist visits, and emergency department visits (Table 3). A relatively small number of participants (10 [2.6%] with free distribution and 17 [4.6%] with usual access) had total health care costs greater than $60 000 (Figure 2). Mean total costs were $4465 (95% CI, −$944 to $9874) lower over 3 years, or $1488 (95% CI, −$315 to $3291) lower per year.

These results build on earlier reports of the CLEAN Meds trial that showed improvements in adherence and health care expenses after 12 and 24 months and mixed effects on surrogate health outcomes.6^,7 The annual reductions in health care spending were similar at 36 months (mean, $1488; median, $547) relative to the previously reported reductions at 24 months (mean, $1222; median, $558).⁷ This trial involving patients in primary care followed up for 3 years showed a larger benefit than 2 trials of improved medicine access conducted among inpatients followed up for approximately 1 year.^10,11 These findings suggest that it may take time for adherence to improve health, and preventive medicines might be relatively more beneficial among unselected outpatients than among recently hospitalized patients. The current findings suggest that promoting health equity by improving medicine access can reduce overall health care costs, thereby adding to prior studies showing that free medicine distribution improves the experiences of patients and clinicians.^12,13 Thus, free medicine distribution may help achieve the quintuple aim that includes both reducing health care spending and improving health equity or fairness in health care and outcomes by ensuring that financial means are not a barrier to realizing the benefits of medicines.⁴ The present findings support a recent call for pharmacoequity, or access to high-quality medicines, “regardless of race and ethnicity, socioeconomic status, or availability of resources”^14(p1793) by demonstrating economic benefits of fair access. By contrast, eliminating out-of-pocket expenses for all health care services increased overall health care spending in 2 large experimental studies, though other benefits were demonstrated.^15,16

Published: May 26, 2023. doi:10.1001/jamahealthforum.2023.1127

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2023 Persaud N et al. JAMA Health Forum.

Corresponding Author: Nav Persaud, MD, Department of Family and Community Medicine, St Michael’s Hospital, Unity Health Toronto, 80 Bond St, Toronto, ON M5B 1X2, Canada ([email protected]).

Author Contributions: Dr Persaud had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Persaud, Boozary, Glazier, Gomes, Hwang, Law, Mamdani, Manns, Morgan, Oh, Pinto, Shah, Sullivan, Umali, Laupacis.

Acquisition, analysis, or interpretation of data: Persaud, Bedard, Gomes, Jüni, Mamdani, Martin, Shah, Umali, Thorpe, Tu, Wu.

Drafting of the manuscript: Persaud.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Persaud, Jüni, Thorpe, Wu.

Obtained funding: Persaud, Bedard, Boozary, Morgan, Laupacis.

Administrative, technical, or material support: Persaud, Bedard, Hwang, Law, Mamdani, Morgan, Pinto, Sullivan, Umali.

Supervision: Persaud.

Conflict of Interest Disclosures: Dr Persaud reported grants from the Canadian Institutes of Health Research, Ontario SPOR Support Unit, and St Michael’s Hospital Foundation during the conduct of the study. Dr Gomes reported grants from the Ontario Ministry of Health outside the submitted work. Dr Law reported personal fees from Health Canada and the Federation of Post-Secondary Educators outside the submitted work. Dr Pinto reported holding a Canadian Institutes of Health Research Applied Public Health Chair and serving as the associate director for clinical research at the University of Toronto Practice-Based Research Network. Dr Shah reported grants from the University of Toronto and holding the Novo Nordisk Research Chair in Equitable Care of Diabetes during the conduct of the study. Ms Wu reported grants from the Canadian Institutes of Health Research, Ontario SPOR Support Unit, and St Michael’s Hospital Foundation during the conduct of the study. No other disclosures were reported.

Funding/Support: This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. This study also received funding from the Canadian Institutes of Health Research. Parts of the study data were compiled and provided by the Canadian Institute for Health Information and the Ontario Ministry of Health. This work is supported by the Canadian Institutes of Health Research (381409), the Ontario SPOR Support Unit (OSSU), and the St Michael’s Hospital Foundation.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: The CLEAN Meds (Carefully Selected and Easily Accessible at No Charge Medications) study team contributors are listed in Supplement 3.

Disclaimer: The analyses, conclusions, opinions, and statements expressed herein are solely those of the authors and do not reflect those of the funding or data sources; no endorsement is intended or should be inferred.

Data Sharing Statement: See Supplement 4.