The cost of potentially inappropriate medications for older adults in Canada: A comparative cross-sectional study.

BACKGROUND: Potentially inappropriate medications (PIMs) are medications whereby the harms may outweigh the benefits for a given individual. Although overprescribed to older adults, their direct costs on the healthcare system are poorly described. METHODS: This was a cross-sectional study of the cost of PIMs for Canadians aged 65 and older, using adapted criteria from the American Geriatrics Society. We examined prescription claims information from the National Prescription Drug Utilization Information System in 2021 and compared these with 2013. The overall levels of inflation-adjusted total annual expenditure on PIMs, average cost per quarterly exposure, and average quarterly exposures to PIMs were calculated in CAD$. RESULTS: Exposure to most categories of PIMs decreased, aside from gabapentinoids, proton pump inhibitors, and antipsychotics, all of which increased. Canadians spent $1 billion on PIMs in 2021, a 33.6% reduction compared with 2013 ($1.5 billion). In 2021, the largest annual expenditures were on proton pump inhibitors ($211 million) and gabapentinoids ($126 million). The quarterly amount spent on PIMs per person exposed decreased from $95 to $57. In terms of mean cost per person, opioids and antipsychotics were highest ($138 and $118 per exposure). Some cost savings may have occurred secondary to an observed decline of 16.4% in the quarterly rate of exposure to PIMs (from 7301 per 10,000 in 2013 to 6106 per 10,000 in 2021). CONCLUSIONS: While expenditures on PIMs have declined in Canada, the overall cost remains high. Prescribing of some seriously harmful classes of PIMs has increased and so directed, scalable interventions are needed.

Factors influencing the effects of policies and interventions to promote the appropriate use of medicines in high-income countries: A rapid realist review.

BACKGROUND: The appropriate use of medicines has long been recognized as a fundamental component of medicine policies. We aimed to extract lessons from published research on how policy contexts and mechanisms can affect the outcomes of national- or health-system level interventions to promote appropriate medicine use (defined as an increase in underutilized medications or decrease in inappropriate medication use). METHODS: We conducted a rapid realist review of published evidence concerning system-level policies to promote the appropriate use of medicines in high-income countries with universal prescription drug coverage. We searched MEDLINE and Embase to identify relevant publications. We used a realist evaluation framework to identify contexts, mechanisms, and outcomes for each intervention and to hypothesize which policy contexts and mechanisms supported successful outcomes in terms of relative changes in the prevalence of use of the specific medication classes targeted. RESULTS: From 1,318 identified studies, 18 met our inclusion criteria. 13 distinct policies were identified. Three main policy-related factors underpinned successful interventions: involving providers and patients through program interventions; central coordination through national agencies dedicated to medicine policies; and the establishment of an explicit and integrated national medicine policy strategy. CONCLUSION: Policymakers can improve coordination of national pharmaceutical policies to reduce harms from inappropriate medicines use, thus improving health outcomes through cost-effective programs.

Effect of Free Medicine Distribution on Health Care Costs in Canada Over 3 Years: A Secondary Analysis of the CLEAN Meds Randomized Clinical Trial.

Importance: Few interventions are proven to reduce total health care costs, and addressing cost-related nonadherence has the potential to do so. Objective: To determine the effect of eliminating out-of-pocket medication fees on total health care costs. Design, Setting, and Participants: This secondary analysis of a multicenter randomized clinical trial using a prespecified outcome took place across 9 primary care sites in Ontario, Canada (6 in Toronto and 3 in rural areas), where health care services are generally publicly funded. Adult patients (≥18 years old) reporting cost-related nonadherence to medicines in the past 12 months were recruited between June 1, 2016, and April 28, 2017, and followed up until April 28, 2020. Data analysis was completed in 2021. Interventions: Access to a comprehensive list of 128 medicines commonly prescribed in ambulatory care with no out-of-pocket costs for 3 years vs usual medicine access. Main Outcome and Measures: Total publicly funded health care costs over 3 years, including costs of hospitalizations. Health care costs were determined using administrative data from Ontario's single-payer health care system, and all costs are reported in Canadian dollars with adjustments for inflation. Results: A total of 747 participants from 9 primary care sites were included in the analysis (mean [SD] age, 51 [14] years; 421 [56.4%] female). Free medicine distribution was associated with a lower median total health care spending over 3 years of $1641 (95% CI, $454-$2792; P = .006). Mean total spending was $4465 (95% CI, -$944 to $9874) lower over the 3-year period. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, eliminating out-of-pocket medication expenses for patients with cost-related nonadherence in primary care was associated with lower health care spending over 3 years. These findings suggest that eliminating out-of-pocket medication costs for patients could reduce overall costs of health care. Trial Registration: ClinicalTrials.gov Identifier: NCT02744963.

Adherence at 2 years with distribution of essential medicines at no charge: The CLEAN Meds randomized clinical trial.

BACKGROUND: Adherence to medicines is low for a variety of reasons, including the cost borne by patients. Some jurisdictions publicly fund medicines for the general population, but many jurisdictions do not, and such policies are contentious. To our knowledge, no trials studying free access to a wide range of medicines have been conducted. METHODS AND FINDINGS: We randomly assigned 786 primary care patients who reported not taking medicines due to cost between June 1, 2016 and April 28, 2017 to either free distribution of essential medicines (n = 395) or to usual medicine access (n = 391). The trial was conducted in Ontario, Canada, where hospital care and physician services are publicly funded for the general population but medicines are not. The trial population was mostly female (56%), younger than 65 years (83%), white (66%), and had a low income from wages as the primary source (56%). The primary outcome was medicine adherence after 2 years. Secondary outcomes included control of diabetes, blood pressure, and low-density lipoprotein (LDL) cholesterol in patients taking relevant treatments and healthcare costs over 2 years. Adherence to all appropriate prescribed medicines was 38.7% in the free distribution group and 28.6% in the usual access group after 2 years (absolute difference 10.1%; 95% confidence interval (CI) 3.3 to 16.9, p = 0.004). There were no statistically significant differences in control of diabetes (hemoglobin A1c 0.27; 95% CI -0.25 to 0.79, p = 0.302), systolic blood pressure (-3.9; 95% CI -9.9 to 2.2, p = 0.210), or LDL cholesterol (0.26; 95% CI -0.08 to 0.60, p = 0.130) based on available data. Total healthcare costs over 2 years were lower with free distribution (difference in median CAN$1,117; 95% CI CAN$445 to CAN$1,778, p = 0.006). In the free distribution group, 51 participants experienced a serious adverse event, while 68 participants in the usual access group experienced a serious adverse event (p = 0.091). Participants were not blinded, and some outcomes depended on participant reports. CONCLUSIONS: In this study, we observed that free distribution of essential medicines to patients with cost-related nonadherence substantially increased adherence, did not affect surrogate health outcomes, and reduced total healthcare costs over 2 years. TRIAL REGISTRATION: ClinicalTrials.gov NCT02744963.

Quantifying the statistical power of monitoring programs for marine protected areas.

Marine Protected Areas (MPAs) are increasingly established globally as a spatial management tool to aid in conservation and fisheries management objectives. Assessing whether MPAs are having the desired effects on populations requires effective monitoring programs. A cornerstone of an effective monitoring program is an assessment of the statistical power of sampling designs to detect changes when they occur. We present a novel approach to power assessment that combines spatial point process models, integral projection models (IPMs) and sampling simulations to assess the power of different sample designs across a network of MPAs. We focus on the use of remotely operated vehicle (ROV) video cameras as the sampling method, though the results could be extended to other sampling methods. We use empirical data from baseline surveys of an example indicator fish species across three MPAs in California, USA as a case study. Spatial models simulated time series of spatial distributions across sites that accounted for the effects of environmental covariates, while IPMs simulated expected trends over time in abundances and sizes of fish. We tested the power of different levels of sampling effort (i.e., the number of 500-m ROV transects) and temporal replication (every 1-3 yr) to detect expected post-MPA changes in fish abundance and biomass. We found that changes in biomass are detectable earlier than changes in abundance. We also found that detectability of MPA effects was higher in sites with higher initial densities. Increasing the sampling effort had a greater effect than increasing sampling frequency on the time taken to achieve high power. High power was best achieved by combining data from multiple sites. Our approach provides a powerful tool to explore the interaction between sampling effort, spatial distributions, population dynamics, and metrics for detecting change in previously fished populations.

Costs and compensation in zooplankton pigmentation under countervailing threats of ultraviolet radiation and predation.

Evolutionary responses to opposing directions of natural selection include trade-offs, where the phenotype balances selective forces, and compensation, where other traits reduce the impact of one selective force. Zooplankton pigmentation protects from ultraviolet radiation (UVR) but attracts visual predators. This trade-off is understudied in the ocean where planktonic larvae in surface waters face ubiquitous UVR and visual predation threats. We tested whether crab larvae can behaviorally reduce UVR risk through downward swimming or expansion of photoprotective chromatophores. Then we examined whether more pigmented larvae are more heavily predated by silverside fish under natural sunlight in the tropics in three UVR treatments (visible light, visible + UVA, visible + UVA + UVB). Lastly, we tested the behavioral chromatophore response of larvae to predation threats in two light treatments. Armases ricordi avoided surface waters after exposure to sunlight with UVR. Armases ricordi, Armases americanum, and Eurypanopeus sp. consistently expanded chromatophores in UVR or visible light, while Mithraculus sculptus and Mithraculus coryphe showed no response. Fish preferred pigmented larvae on sunnier days in visible light lacking UVR. Lastly, both M. coryphe and M. sculptus unexpectedly expanded chromatophores in fish cues, but responses were inconsistent over trials and across light treatments. The more consistent larval responses to UVR than to predator cues and the lack of predator preferences in natural light conditions suggest that UVR may have a stronger influence on pigmentation than predation. This study improves our understanding of planktonic adaptation to countervailing selection caused by visual predation and exposure to UVR.

Variation in the prescription drugs covered by health systems across high-income countries: A review of and recommendations for the academic literature.

BACKGROUND: Because not all medicines are equally safe, effective, and affordable, health systems often use formularies to define explicitly which medicines will be included and excluded from coverage. OBJECTIVE: We sought to synthesize methods and findings from published studies of formulary variation across health systems in high-income countries. METHODS: We conducted a systematic review of peer-reviewed research papers published from 2000 to 2017, inclusively. Because of the heterogeneous nature of the literature, we used an inductive approach to summarize methods and findings. RESULTS: Nine studies met our study inclusion criteria. Included studies used a variety of methods for selecting medicines for analysis, for measuring coverage levels, and for measuring concordance between formularies. Studies assessing variations in coverage of all licensed medicines and found lower rates of cross-national coverage variation than studies of coverage for selected specialty drugs and indications. The one study that focused on coverage of high-volume medicines found the most complete and consistent levels of formulary listings across countries. CONCLUSION: Although published studies contain interesting findings that likely have prompted discussions about their policy implications, the literature can be improved with greater transparency concerning the overarching objective of work in this area and more rigor concerning the selection, analysis, and reporting of data.