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.

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

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.

Photoprotective benefits of pigmentation in the transparent plankton community: a comparative species experimental test.

Plankton live under the countervailing selective pressures of predation and ultraviolet radiation (UVR). In lakes, zooplankton are transparent reducing visibility to predatory fishes but are pigmented in the absence of fishes, hypothetically reducing UVR damage. In the sea, planktivorous fishes are widespread, so plankton typically are transparent and ascend to productive surface waters at night to forage and descend during the day to reduce visibility to predators. However, larvae of some species face the unique constraint of traveling in surface currents in the daytime during migrations between adult and larval habitats. We would expect these larvae to be transparent since companion studies demonstrated increased predation risk of pigmented larvae under strong sunlight. Paradoxically, larvae range from being darkly to lightly pigmented. We hypothesize that some larvae are more heavily pigmented to reduce UVR damage, while other species travelling in subsurface currents with low UVR might be more transparent. Linking larval morphology to depth-dependent selective pressures would add a key element to help improve predictions of larval vertical distributions, which are important for simulating larval transport trajectories. We quantitatively tested the hypothesis that selection may have favored photoprotective pigmentation for larvae in the predominantly transparent plankton community while testing the differential effects of UVA and UVB radiation. We measured larval pigmentation of 12 species of crabs and exposed them to visible light only, visible + UVA, or visible + UVA + UVB in the tropics. Controlling for phylogeny, more pigmented species survived UVR better than less pigmented species, especially on sunnier days, though intraspecific comparisons for four species were equivocal. Most species died even from UVA exposure, which has long been regarded as relatively harmless despite penetrating deeper underwater than UVB. Thus, we demonstrate with a phylogenetically controlled analysis that crab larvae are pigmented in the predominantly transparent planktonic community to protect from UVR, improving our understanding of the selective forces acting on animal coloration and the factors determining planktonic distributions, survival, and dispersal. This linkage of morphology with susceptibility will be important for developing mechanistic models of environmental stress responses to better predict larval dispersal in current and future climates.

Patterns of borrowing to finance out-of-pocket prescription drug costs in Canada: a descriptive analysis.

BACKGROUND: Out-of-pocket drug costs lead many Canadians to engage in cost-related nonadherence to prescription medications, but our understanding of other consequences such as borrowing money remains incomplete. In this descriptive study, we sought to quantify the frequency of borrowing to pay for prescription drugs in Canada and characteristics of Canadians who borrowed money for this purpose. METHODS: In partnership with Statistics Canada, we designed and administered a cross-sectional rapid-response module in the Canadian Community Health Survey administered by telephone to Canadians aged 12 years or more between January and June 2016. We restricted our analyses to participants who responded to the question regarding borrowing money to pay for prescription drugs and used logistic regression to identify characteristics associated with borrowing. RESULTS: A total of 28 091 Canadians responded to the survey (overall response rate 61.8%). The weighted proportion of respondents who reported having borrowed money to pay for prescription drugs in the previous year was 2.5% (95% confidence interval 2.2%-2.8%), an estimated 731 000 Canadians. The odds of borrowing were higher among younger adults, people in poor health and people lacking prescription drug insurance. Other factors associated with increased adjusted odds of borrowing were having 2 or more chronic conditions, low household income and higher out-of-pocket prescription drug costs. INTERPRETATION: Many Canadians reported borrowing money to pay for out-of-pocket prescription drug costs, and borrowing was more prevalent among already vulnerable groups that also report other compensatory behaviours to address challenges in paying for prescription drugs. Future research should investigate policy responses intended to increase equity in access to prescription drugs.

Prescription drug coverage in Canada: a review of the economic, policy and political considerations for universal pharmacare.

BACKGROUND: Canadians have long been proud of their universal health insurance system, which publicly funds the cost of physician visits and hospitalizations at the point of care. Prescription drugs however, have been subject to a patchwork of public and private coverage which is frequently inefficient and creates access barriers to necessary medicine for many Canadians. METHODS: A narrative review was undertaken to understand the important economic, policy and political considerations regarding implementation of universal prescription drug access in Canada (pan-Canadian pharmacare). PubMed, SCOPUS and google scholar were searched for relevant citations. Citation trails were followed for additional information sources. Published books, public reports, press releases, policy papers, government webpages and other forms of gray literature were collected from iterative internet searches to provide a complete view of the current state on this topic. MAIN FINDINGS: Regarding health economics, all five of the reviewed pharmacare simulation models have shown reductions in annual prescription drug expenditure. However, differing policy and cost assumptions have resulted in a wide range of cost-saving estimates between models. In terms of policy, a single-payer, 'first-dollar' coverage model, using a minimum national formulary, is the model most frequently advocated by the academic community, healthcare professions and many public and patient groups. In contrast, a multi-payer, catastrophic 'last-dollar' coverage model, more similar to the current "patchwork" state of public and private coverage, is preferred by industry drug manufacturers and private health insurance companies. Primary concerns from the detractors of universal, single-payer, 'first-dollar' coverage are the financing required for its implementation and the access barriers that may be created for certain patient populations that are not majorly present in the current public-private payer mix. CONCLUSION: Canada patiently awaits to see how the issue of prescription drug coverage will be resolved through the work of the Advisory Council on the Implementation of National Pharmacare. The overarching and ongoing discourse on policy and program implementation may be construed as a political debate informed by divergent public and private interests.

An analysis of expenditures on primary care prescription drugs in the United States versus ten comparable countries.

OBJECTIVE: We sought to estimate size and sources of differences in per capita expenditures on primary care medications in the US versus ten comparable countries combined: Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, and the United Kingdom. METHODS: Using market research data on year 2015 volumes and sales of medicines, we measure total per capita expenditures on six categories of primary care prescription drugs: hypertension treatments, pain medications, lipid lowing medicines, non-insulin diabetes treatments, gastrointestinal preparations, and antidepressants. We quantified the contributions of five drivers of the observed differences in per capita expenditures. RESULTS: We estimated that the US spent 203% more per capita on primary care pharmaceuticals than did the ten comparable countries. Despite the difference in spending levels, on average, Americans actually purchased 12% fewer days of related therapies than residents of the comparator countries. Most of the observed difference in expenditures was due to higher transaction prices of medicines and the use of a more expensive mix of medicines in the US. CONCLUSIONS: If utilization patterns and pharmaceutical prices in the US were similar to those in the 10 comparator countries combined, total spending on primary care pharmaceuticals would fall by 30% or more. Such evidence on the level and drivers of US pharmaceutical expenditures should inform policies in this sector.

The consequences of patient charges for prescription drugs in Canada: a cross-sectional survey.

BACKGROUND: Many Canadians face substantial out-of-pocket charges for prescription drugs. Prior work suggests that this causes some patients to not take their medications as prescribed; however, we have little understanding of whether charges for prescription medicines lead patients to forego basic needs or to use more health care services. Our study aimed to quantify the consequences of patient charges for medicines in Canada. METHODS: As part of the 2016 Canadian Community Health Survey, we designed and fielded cross-sectional questions to 28 091 Canadians regarding prescription drug affordability, consequent use of health care services and trade-offs with other expenditures. We calculated weighted population estimates and proportions, and used logistic regression to determine which patient characteristics were associated with these behaviours. RESULTS: Overall, 5.5% (95% confidence interval 5.1%-6.0%) of Canadians reported being unable to afford 1 or more drugs in the prior year, representing 8.2% of those with at least 1 prescription. Drugs for mental health conditions were the most commonly reported drug class for cost-related nonadherence. About 303 000 Canadians had additional doctor visits, about 93 000 sought care in the emergency department, and about 26 000 were admitted to hospital at the population level. Many Canadians forewent basic needs such as food (about 730 000 people), heat (about 238 000) and other health care expenses (about 239 000) because of drug costs. These outcomes were more common among females, younger adults, Aboriginal peoples, those with poorer health status, those lacking drug insurance and those with lower income. INTERPRETATION: Out-of-pocket charges for medicines for Canadians are associated with foregoing prescription drugs and other necessities as well as use of additional health care services. Changes to protect vulnerable populations from drug costs might reduce these negative outcomes.

Planktonic Subsidies to Surf-Zone and Intertidal Communities.

Plankton are transported onshore, providing subsidies of food and new recruits to surf-zone and intertidal communities. The transport of plankton to the surf zone is influenced by wind, wave, and tidal forcing, and whether they enter the surf zone depends on alongshore variation in surf-zone hydrodynamics caused by the interaction of breaking waves with coastal morphology. Areas with gently sloping shores and wide surf zones typically have orders-of-magnitude-higher concentrations of plankton in the surf zone and dense larval settlement in intertidal communities because of the presence of bathymetric rip currents, which are absent in areas with steep shores and narrow surf zones. These striking differences in subsidies have profound consequences; areas with greater subsidies support more productive surf-zone communities and possibly more productive rocky intertidal communities. Recognition of the importance of spatial subsidies for rocky community dynamics has recently advanced ecological theory, and incorporating surf-zone hydrodynamics would be an especially fruitful line of investigation.