Systematic Review of Outcomes for Assessment of Medication Adherence Enhancing Interventions: An ISPOR Special Interest Group Report.

OBJECTIVES: The lack of universal guidance on outcome measures for evaluating medication adherence enhancing interventions (MAEIs) poses a challenge for assessing their effectiveness. This literature review aimed to provide a systematic overview of outcome measures currently used for the value assessment of MAEIs. METHODS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and searched MEDLINE, PsycINFO, Scopus, CINAHL, and Academic Search Complete for randomized and nonrandomized clinical trials, prospective cohort studies, model-based economic evaluations, and value frameworks published in English between January 2010 and September 2020. Two independent reviewers screened all titles and abstracts, followed by a full-text review. Due to the large number of relevant studies, data extraction was limited to articles published between January 2018 and September 2020. We collected data on the general characteristics of the study, the type of intervention, and the outcomes measured. RESULTS: We screened 14 685 records and identified 308 articles for data extraction. Behavioral interventions were the most common (n = 143), followed by educational interventions (n = 110) and mixed-method interventions (n = 73). Outcomes were clustered into 7 categories with medication adherence (n = 286) being the most frequently measured, followed by clinical outcomes (n = 155), health-related quality of life (n = 57), resource use (n = 43), patient satisfaction (n = 31), economic outcomes (n = 18), and other outcomes (n = 76). CONCLUSIONS: Various outcomes measures have been used to evaluate MAEIs, with only a small number of studies exploring economic and patient-reported outcomes. Future research is warranted to develop a consensus-based set of criteria for assessing MAEIs to facilitate the comparison of interventions and enable informed decision making.

Understanding the evolution of coverage policies for prophylaxis treatments of hemophilia A without inhibitors: a payer Delphi panel.

BACKGROUND: The landscape for hemophilia A prophylaxis is rapidly expanding from factor VIII replacement therapy to include novel treatments such as nonfactor replacement therapies that may enhance coagulation (e.g., emicizumab) or inhibit anticoagulant pathways (e.g., fitusiran and concizumab). For payers, this expansion presents challenges in balancing well-established treatments with new options that cost more and have lesser known real-world safety and efficacy. OBJECTIVE: To evaluate likely coverage practices for hemophilia A prophylaxis therapies among U.S. payers given evolving real-world data on safety and efficacy. METHODS: A 3-round modified Delphi process was conducted with representatives of U.S. commercial health plans who had considerable expertise in managing populations of patients with hemophilia. Round 1 consisted of an online questionnaire; round 2 involved an online discussion about the aggregated results from round 1; and round 3 allowed participants to revise their responses from round 1 based on insights gained during round 2. Questions elicited ratings, rankings, and estimates on access restrictions based on given safety and efficacy information for hemophilia A prophylaxis therapies. Consensus was reached if ≥ 74% of panelists (14 of 19) were within 1 SD of the median group estimate during round 3. RESULTS: 19 Payers participated in the research. Among them, 94% dealt with commercial insurance, 94% with Medicare, and 81% with Medicaid; 79% had spent ≥ 5 years in their current role. Panelists reported limited access restrictions on hemophilia A prophylaxis therapies; the most common restrictions were prior authorization (n = 16, 84%) and quantity level limits (n = 13, 67%). Tiering and step therapy were reported by 7 respondents (39%). Respondents agreed that there was an 80% median likelihood that ≥ 9 additional patients with any safety event (e.g., thrombotic event, death) per year would trigger access restrictions, with the median likelihood of restrictions increasing to 95% for another ≥ 10 patients with safety events per year. Respondents also agreed that > 5 thrombotic events requiring treatment per patient per year would have a 98% median likelihood of leading to access restrictions and that ≥ 5 years of real-world safety and efficacy data would be highly likely (95% median likelihood) to affect coverage decisions. Noncoverage was highly unlikely (ranked fifth or sixth of 6 by 14 respondents), as was no restriction-coverage parity (ranked sixth of 6 by 10 respondents). All else being equal, cost continues to affect access policies, with respondents agreeing that a 13%-30% difference in net cost may lead to preferred formulary treatment for a drug with superior efficacy and noninferior safety, inferior efficacy and noninferior safety, or noninferior efficacy and inferior safety. CONCLUSIONS: Payers prefer treatments with well-understood efficacy, safety, and cost over newer treatments with uncertain long-term effects. Relatively unrestricted access to legacy and new hemophilia A prophylaxis will likely continue unless additional real-world safety concerns or major cost differences emerge. DISCLOSURES: Financial support for this study was provided by Takeda Pharmaceutical Company, which was involved in study concept and design. Graf, Tuly, Harley, and Pednekar are employees of PRECISIONheor, a research consultancy to the health and life sciences industries that was contracted by Takeda to conduct this study and write the manuscript. Batt served as a consultant on this project through PRECISIONheor.

For which diseases do broader value elements matter most? An evaluation across 20 ICER evidence reports.

BACKGROUND: U.S. value framework developers such as the Institute for Clinical and Economic Review (ICER) use cost-effectiveness analysis to value new health care technologies. Often, these value assessment frameworks use a health system perspective without fully accounting for societal and broader benefits and costs of an intervention. Although there is ongoing debate about the most appropriate methods for including broader value elements in value assessment, it remains unclear whether the inclusion of these value elements is likely to affect the quantitative estimates of treatment value. OBJECTIVE: To assess variations in the relevance of broader value elements to cost-effectiveness analysis across diseases. METHODS: Thirty-two broader value elements (e.g., caregiver burden, health equity, real option value, productivity) not traditionally included in health technology assessments were identified through a targeted literature review. Evidence reports published by ICER between July 2017 and January 2020 were evaluated to identify which broader value elements were discussed as relevant to each disease in the report text. The study examined whether there were associations among ICER's discussion of broader value elements, rare disease status, treatment cost, estimated treatment cost-effectiveness, and ICER committee voting results for contextual considerations and additional benefits/disadvantages. RESULTS: The most commonly cited broader value element category in the ICER evidence reports was household and leisure (e.g., absenteeism from normal activities and caregiver burden). More value elements were cited for inherited retinal disease (19 elements) and sickle cell disease (18 elements) than for other diseases. Cardiovascular disease and diabetes had the fewest number of value elements cited (7 elements). Rare diseases were more likely to have broader value elements cited compared with nonrare diseases (15.9 vs. 11.5, P < 0.001). Treatments with higher (i.e., less favorable) incremental cost-effectiveness ratios were more likely to have a greater number of broader value elements cited (ρ = 0.625, P < 0.001). CONCLUSIONS: The presence of broader value elements varied across diseases, with less cost-effective treatments more likely to have a higher number of relevant broader value elements. Inclusion of all relevant value elements in value assessments will more appropriately incentivize innovation and improve allocation of research funding. DISCLOSURES: This study was sponsored by Novartis Pharmaceutical Corporation. At the time of this study, Shafrin was employed by PRECISIONheor, a consultancy to the life sciences industry that received financial support from Novartis to conduct this study. Dennen, Pednekar, and Birch are employed by PRECISIONheor. Bhor was an employee of Novartis Pharmaceutical Corporation at the time this research was conducted and manuscript was developed and reports grants from Novartis, unrelated to this work. Kanter has served on scientific advisory boards and steering committees for and reports receiving consulting fees from Novartis Pharmaceutical Corporation and is a site principal investigator on studies funded by Novartis Pharmaceutical Corporation. Kantar also reports support from Sickle Cell Disease Association of America Inc. and National Heart, Lung, and Blood Institute, unrelated to this work. Neumann reports advisory boards or consulting fees from Novartis Pharmaceutical Corporation and PRECISIONheor, as well as advisory boards or consulting fees unrelated to this study from AbbVie, Amgen, Avexis, Bayer, Congressional Budget Office, Janssen, Merck, Novartis, Novo Nordisk, Precision Health Economics, Veritech, Vertex; funding from The CEA Registry Sponsors by various pharmaceutical and medical device companies; and grants from Amgen, Lundbeck, Bill and Melinda Gates Foundation, National Pharmaceutical Council, Alzheimer's Association, and the National Institutes for Health.

Association of Medication Adherence with Hospital Utilization and Costs Among Elderly with Diabetes Enrolled in a State Pharmaceutical Assistance Program.

BACKGROUND: Medication adherence is crucial for the successful treatment among elderly patients with diabetes taking oral antidiabetic medications (OAMs). Cost of medications, lack of insurance coverage, and low income are major contributing factors towards medication nonadherence. State pharmaceutical assistance programs (SPAPs) provide medications at little or no cost to income-eligible patients and have potential to improve medication adherence among elderly patients. Despite this, limited research has focused on the association of medication adherence with health care utilization among elderly patients enrolled in SPAPs, and inclusion of health care costs as an outcome is even rarer. OBJECTIVE: To evaluate the relationship between adherence to OAMs and hospital utilization and costs among elderly patients with diabetes who were enrolled in a SPAP. METHODS: This retrospective observational study included elderly patients with diabetes enrolled in Pennsylvania's Pharmaceutical Assistance Contract for the Elderly (PACE) program in 2015. Medication adherence was estimated as the proportion of days covered (PDC; adherent: PDC≥80%, nonadherent: PDC < 80%). Hospital utilization and costs were estimated using hospital discharge records from the Pennsylvania Health Care Cost Containment Council. Multiple adjusted regression analyses were used to examine the association of medication adherence with hospital utilization (all-cause and diabetes-related number of inpatient hospital visits and length of stay [LOS]) and costs. RESULTS: Among 9,497 elderly PACE enrollees with diabetes, 81% were adherent, and 21% were hospitalized. Compared with adherent patients, patients who were nonadherent to OAMs had twice the odds of all-cause and diabetes-related hospitalization. Controlling for covariates, nonadherent patients had 27% more all-cause (95% CI = 9%-36%) and 21% more diabetes-related (95% CI = 5%-40%) hospital visits than adherent patients. Covariate-adjusted LOS for nonadherent patients was 24% longer than that of adherent patients for all-cause hospitalization (95% CI = 1.171-1.311) and 12.7% longer for diabetes-related hospitalization (95% CI = 1.036-1.227). Medication nonadherence was associated with significantly greater all-cause ($22,670 vs. $16,383; P < 0.0001) and diabetes-related ($13,518 vs. $12,634; P = 0.0003) hospitalization costs. CONCLUSIONS: Among SPAP-enrolled elderly patients, nonadherence to OAMs was significantly associated with increased risk of hospitalization, longer hospital stays, and greater hospitalization costs. Attention is needed to improve medication adherence among elderly receiving financial assistance to pay their prescriptions to reduce economic burden on the health care system. DISCLOSURES: No outside funding supported this study. The authors have nothing to disclose.

Mapping pharmacy deserts and determining accessibility to community pharmacy services for elderly enrolled in a State Pharmaceutical Assistance Program.

OBJECTIVES: Limited studies have investigated geographic accessibility to a nearby community pharmacy for elderly which is an essential determinant of the access to medications and pharmacy services. This research identified pharmacy deserts and investigated availability of different types of community pharmacies and their services for elderly enrolled in a State Pharmaceutical Assistance Program (SPAP). METHODS: The state of Pennsylvania in the US was used as a case to demonstrate the geographic accessibility to community pharmacy and services for elderly enrolled in SPAP. The locations of community pharmacies and households of elderly enrolled in SPAP were derived from Pharmaceutical Assistance Contract for the Elderly programs' database. The street addresses were geocoded and the distance to a nearby community pharmacy was calculated for study sample using the haversine formula. The demographic and geographic data were aggregated to Census Tracts and pharmacy deserts were identified using the predefined criteria. Descriptive statistical analysis was used to determine whether there are statistical differences in the socio-demographic profiles and distribution of different types of community pharmacies and their services in pharmacy deserts and non-deserts. This research used hot spot analyses at county level to identify clusters of pharmacy deserts, areas with high concentration of different racial/ethnic groups and clusters of high densities of chain and independent pharmacies. RESULTS: The Spatial analysis revealed that 39% and 61% Census Tracts in Pennsylvania were pharmacy deserts and non-deserts respectively (p < 0.001). Pharmacy deserts were found to have significantly more females, married and white elderly and fewer blacks and Hispanics compared to pharmacy non-deserts. Pharmacy deserts had significantly fewer chain and independent pharmacies and less delivery and 24-hour services in pharmacies than pharmacy non-deserts. Hot spot analyses showed that clusters of pharmacy deserts were more concentrated in southcentral, northwest and northeast regions of the state which represent rural areas and overlapped with clusters of high concentration of white individuals. CONCLUSIONS: The findings suggest that urban-rural inequality, racial/ethnic disparity and differences in availability of pharmacies and their services exist between pharmacy deserts and non-deserts. The methodological approach and analyses used in this study can also be applied to other public health programs to evaluate the coverage and breadth of public health services.