Contracting retail pharmacies as a source of essential medicines for public sector clients in low- and middle-income countries: a scoping review of key considerations, challenges, and opportunities.

BACKGROUND: Insurances in high-income countries (HIC) often contract with private community pharmacies to dispense medicines to outpatients. In contrast, dispensing of medicines in low- and middle-income countries (LMICs) often lacks such contractual arrangements. Furthermore, many LMICs lack sufficient investment in supply chains and financial and human resources to guarantee stock levels and services at public medicine-dispensing institutions. Countries striving to achieve universal health coverage (UHC) can, in principle, incorporate retail pharmacies into their supply chains to expand access to essential medicines (EMs). The objectives of this paper are (a) to identify and analyze key considerations, opportunities and challenges for public payers when contracting out the supply and dispensing of medicines to retail pharmacies and (b) to provide examples of strategies and policies to address these challenges. METHODS: A targeted literature strategy was used to conduct this scoping review. We created an analytical framework of key dimensions: (1) governance (including medicine and pharmacy regulation); (2) contracting (3) reimbursement; (4) medicine affordability (5) equitable access; and (6) quality of care (including 'patient-centered' pharmaceutical care). Using this framework, we selected a mix of three HIC and four LMIC case studies and analyzed the opportunities and challenges encountered when contracting retail pharmacies. RESULTS: From this analysis, we identified a set of opportunities and challenges that should be considered by public payers considering public-private contracting: (1) balancing business viability with medicine affordability; (2) incentivizing equitable access to medicines; (3) ensuring quality of care and delivery of services; (4) ensuring product quality; (5) task-sharing from primary care providers to pharmacies and (6) securing human resources and related capacity constraints to ensure sustainability of the contract. CONCLUSION: Public-private partnerships offer opportunities to improve access to EMs. Nonetheless, managing these agreements is complex and is influenced by a variety of factors. For effective contractual partnerships, a systems approach is needed in which business, industry and regulatory contexts are considered in tandem with the health system. Special attention should be devoted to rapidly changing health contexts and systems, such as changes in patient preferences and market developments brought about by the COVID-19 pandemic.

Out-of-pocket expenditure on medicines in Bangladesh: An analysis of the national household income and expenditure survey 2016-17.

BACKGROUND AND OBJECTIVES: High out-of-pocket expenditures (OOPE) increases the probability that households will become impoverished or will forgo needed care. The aim of this paper is to study household medicines expenditure and its associated determining factors to develop policies to protect households from financial hardship. METHODS: The present cross-sectional and population-level study used the Bangladesh 2016-17 National Household Income and Expenditure Survey (HIES). The final sample size was 46,080 households. We analyzed the probability of OOPE for medicines, the share of total OOPE due to medicines out of total OOPE in health (reported as a ratio between zero and one), the OOPE amount for medicines reported (in United States Dollars), and the share of OOPE amount on medicines out of total household expenditure (reported as a ratio between zero and one). Predictors of analyzed outcomes were identified using three regression models. RESULTS: Out of those households who spent on healthcare, the probability of having any OOPE on medicines was 87.9%. Of those who spent on medicines, the median monthly expenditure was US$3.03. The poorest households spent 9.97% of their total household expenditure as OOPE on medicines, nearly double that of the wealthiest households (5.86%). The characteristic which showed the most significant correlation to a high OOPE on medicines was the presence of chronic diseases, especially cancer. Twenty six percent of all surveyed households spend more than 10% of their OOPE on medicines. CONCLUSIONS: Our study shows that financial protection should be targeted at the poorest quintiles and such protection should include enrollment of rural households. Further, outpatient medicines benefits should include those for non-communicable diseases (NCDs).

Health System Capacity and Access Barriers to Diagnosis and Treatment of CVD and Diabetes in Nepal.

Background: Universal access to essential medicines and routine diagnostics is required to combat the growing burden of cardiovascular disease (CVD) and diabetes. Evaluating health systems and various access dimensions availability, affordability, accessibility, acceptability, and quality is crucial yet rarely performed, especially in low- and middle-income countries. Objective: To evaluate health system capacity and barriers in accessing diagnostics and essential medicines for CVD and diabetes in Nepal. Methods: We conducted a WHO/HAI nationally-representative survey in 45 health-facilities (public-sector: 11; private-sector: 34) in Nepal to collect availability and price data for 21 essential medicines for treating CVD and diabetes, during MayJuly 2017. Data for 13 routine diagnostics was obtained in 12 health facilities. Medicines were considered unaffordable if the lowest paid worker spends >1 days wage to purchase a monthly supply. To evaluate accessibility, we conducted facility exit interviews among 636 CVD patients. Accessibility (e.g., private-public health facility mix, travel to hospital/pharmacy) and acceptability (i.e. Nepals adoption of WHO Essential Medicine List, and patient medication adherence) were summarized using descriptive statistics, and we conducted a systematic review of relevant literature. We did not evaluate medicine quality. Results: We found that mean availability of generic medicines is low (<50%) in both public and private sectors, and less than one-third medicines met WHOs availability target (80%). Mean (SD) availability of diagnostics was 73.1% (26.8%). Essential medicines appear locally unaffordable. On average, the lowest-paid worker would spend 1.03 (public-sector) and 1.26 (private-sector) days wages to purchase a monthly supply. For a person undergoing CVD secondary preventive-interventions in the private sector, the associated expenditure would be 7.511.2% of monthly household income. Exit-interviews suggest that a long/expensive commute to health-facilities and poor medicine affordability constrain access. Conclusions: This study highlights critical gaps in Nepals health system capacity to offer basic health services to CVD and diabetes patients, owing to low availability, poor affordability and accessibility of essential medicines and diagnostics. Research and policy initiatives are needed to ensure uninterrupted supply of affordable essential medicines and diagnostics.

The implementation of the bioequivalence certification policy in Chile: An analysis of market authorization data.

BACKGROUND: Affordability is a key barrier to access to medicines. Generic medicines policies can address this barrier and promote access. Successful uptake of generic medicines depends, in part, on ensuring that these products are interchangeable with reference products. Typically, bioequivalence certification is established in order to demonstrate such interchangeability. OBJECTIVE: To study the implementation of the bioequivalence certification policy in Chile. METHODS: We used Chilean Market Regulatory Authority data for analysis to study the number of products that obtained bioequivalence certification, the time until bioequivalence certification and associated factors to obtain bioequivalence. RESULTS: As of January 2017, out of 2,336 products with a valid market authorization containing at least one of the 167 APIs that required BE certification, 1,026 products actually have BE certification (1,026/2,336, 43.9% compliance). Where data were available, the time between submission of the market authorization as a bioequivalent product to final authorization by the national medicine regulatory authority for most products varied between 4-6 months. The fraction of all BE products containing a given API out of the total marketed products containing that API varies considerably, e.g. for the API olmesartan there was only a single BE product marketed, the API diclofenac had none. CONCLUSIONS: Although the implementation of Chile's bioequivalence policy increased the number of bioequivalent products, over 50% of generic products requiring bioequivalence that did not obtain this certification. Also for some of the API none or very few BE products are marketed which limits the success of a substitution policy. Further studies are required to identify the apparent lack of incentives to obtain bioequivalence certification. Studies of sales volumes and prices of the products are needed to identify whether generic products without bioequivalence certification either become bioequivalent or eventually exit the market.

The implementation of the bioequivalence certification policy in Chile: an analysis of market authorization data

Affordability is a key barrier to access to medicines. Generic medicines policies can address this barrier and promote access. Successful uptake of generic medicines depends, in part, on ensuring that these products are interchangeable with reference products. Typically, bioequivalence certification is established in order to demonstrate such interchangeability. To study the implementation of the bioequivalence certification policy in Chile. We used Chilean Market Regulatory Authority data for analysis to study the number of products that obtained bioequivalence certification, the time until bioequivalence certification and associated factors to obtain bioequivalence. As of January 2017, out of 2,336 products with a valid market authorization containing at least one of the 167 APIs that required BE certification, 1,026 products actually have BE certification (1,026/2,336, 43.9% compliance). Where data were available, the time between submission of the market authorization as a bioequivalent product to final authorization by the national medicine regulatory authority for most products varied between 4-6 months. The fraction of all BE products containing a given API out of the total marketed products containing that API varies considerably, e.g. for the API olmesartan there was only a single BE product marketed, the API diclofenac had none. Although the implementation of Chile's bioequivalence policy increased the number of bioequivalent products, over 50% of generic products requiring bioequivalence that did not obtain this certification. Also for some of the API none or very few BE products are marketed which limits the success of a substitution policy. Further studies are required to identify the apparent lack of incentives to obtain bioequivalence certification. Studies of sales volumes and prices of the products are needed to identify whether generic products without bioequivalence certification either become bioequivalent or eventually exit the market.

Evaluation of the effects of a generic substitution policy implemented in Chile

Chile implemented a generic substitution policy in 2014 to improve access to medicines. This study aims to measure if the generic substitution policy had an effect on the sales volume and prices of referent and the branded generic products with demonstrated bioequivalence (BEQ) in the private pharmaceutical market. The volume and total private sales of medicines sold at private sector retail outlets between November 2011 and October 2016 were considered in the analysis. We calculated the total number of daily defined doses (DDD) by adding up the number of DDDs of different presentations with the active pharmaceutical ingredient (API). We determined the ratio of the median prices of all BEQ per DDD presentations compared with the median price of the corresponding referent presentations per DDD in 2011 and 2016. Sixteen APIs representing 231 different conventional-release presentations were included in the analysis. Overall, the volume of sales of the referent products decreased over time after the intervention. However, this reduction was not mirrored by an increase in the corresponding branded generic BEQ volumes overall. In all cases, the median price per DDD of the referent was higher than its BEQ counterpart in 2011 and 2016. Since referent products are more costly than branded BEQ generic products, reducing their consumption-and increasing the BEQ availability-should improve access to medicines in Chile. However, this must be accompanied by promotion of BEQ products to ensure savings for consumers in the long term. Future research should focus on identifying facilitating and inhibiting factors of generic substitution.

Impacts of intellectual property provisions in trade treaties on access to medicine in low and middle income countries: a systematic review.

BACKGROUND: We present a systematic review describing ex-ante and ex-post evaluations of the impacts of intellectual property provisions in trade treaties on access to medicine in low and middle income countries. These evaluations focused on multilateral and bilateral trade agreements. We ascertained which IP provisions impacting access to medicines were the focus of these evaluations. We provide a further research agenda related to investigating the effect of trade agreement's intellectual property provisions on access to medicines. We followed systematic review guidelines with 7 different databases to identify post-2000 ex ante and ex post evaluations of trade treaties on access to medicines in low and middle-income countries. We included only quantitative ex-ante studies that used structural modeling and simulations to derive quantitative predictions and ex-post studies that utilized empirical data and econometric techniques to quantify the effects of intellectual property provisions in free trade agreements on host country's pharmaceutical industry. The search strategy identified 744 titles after removal of duplicates. We identified 14 studies that fulfilled all eligibility; 7 studies are ex-ante and 7 are ex-post. The studies looked at medicine price and cost, affordability, welfare effects and speed of medicine market launch. Changes in intellectual property policy due to the implementation of trade agreements affect price, medicines expenditure and sales, consumer welfare, and ultimately the affordability, of medicines. The direction and magnitude of the price effects differ between ex-ante and ex-post studies. Further, the reported impacts of policy changes due to trade agreements on medicine access seem clearly multifactorial. CONCLUSION: Both ex ante and ex post methods have advantages and limitations and, on balance, both types report, for the most part, an increase in price and a decrease in consumer welfare with imposition of intellectual property protection in trade agreements. The main differences between these studies are in the magnitude of the changes. There is a gap in our empirical understanding of the mechanisms through which such changes affect access to medicines and which outcomes relevant to access are most affected by which type of changes in intellectual property policy and law.

Is Taiwan's National Health Insurance a perfect system? Problems related to health care utilization of the aboriginal population in rural townships.

National Health Insurance (NHI) was implemented in Taiwan in 1995, and has significantly increased coverage to 99% of the population. The implementation of NHI has had large impacts on health disparities. Despite that, the NHI faces multiple challenges, including the condition of "coverage without access" among the Taiwanese aboriginal population, mostly residing in mountainous townships and experiencing lower socioeconomic status, decreased health outcomes, and limited access to adequate high-quality health care services. This paper summarizes the persistent health gap and the differences in health care utilization and health outcomes between the aboriginal population in rural townships and urban populations in Taiwan. Mountainous townships face challenges including lack of access to high-quality health care services and limited medical resources. Further policy recommendations and current progress are highlighted and discussed.

Disproportionate Exposure to Antibiotics in Children at Risk for Invasive Pneumococcal Disease: Potential for Emerging Resistance and Opportunity for Antibiotic Stewardship.

We compared antibiotic prescribing for children with and those without an underlying chronic condition associated with increased risk for invasive pneumococcal disease. Children with a chronic condition had significantly greater cumulative exposure to antibiotics and higher rates of prescriptions per person-year than those without a chronic condition; this population is at increased risk for the emergence of multidrug-resistant pathogens.

Retrospective analysis of long-term gastrointestinal symptoms after Clostridium difficile infection in a nonelderly cohort.

Elderly patients and those with comorbid conditions are at high risk for poor outcomes after Clostridium difficile infection (CDI) but outcomes in a healthier, nonelderly population are not well described. We sought to investigate gastrointestinal diagnoses and CDI during hospitalizations in the 24 to 36 months after an initial episode of CDI in nonelderly patients in a cohort with an overall low prevalence of comorbid conditions. We performed a retrospective analysis of hospital admissions from 2010-2013 using the Truven MarketScan database of employment-based private insurance claims. Subjects <65 years of age and their adult dependents (> = 18 years old); a CDI diagnosis in 2011 (index date); at least 12 months of pre-index continuous enrollment; and 24-36 months of continuous post-index enrollment were included. The 12 months of each subject's enrollment prior to the index date for a CDI served as the reference period for the analyses of that subject's post-CDI time periods. Hospital claims during the follow-up period were evaluated for gastrointestinal diagnoses and/or CDI ICD-9 codes. The risk of gastrointestinal diagnoses was assessed using Cox proportional hazards models adjusted for a pre-specified set of baseline demographic and clinical factors. During 2011, 5,632 subjects with CDI met the inclusion criteria for our study. The risk of gastrointestinal diagnoses in patients with a CDI diagnostic code for the same admission was almost 8-fold higher 3 months post-CDI (hazard ratio (HR) = 7.56; 95% confidence interval (CI): 2.97-19.19) than for subjects without CDI and remained statistically significant until month 24 (HR = 1.47; 95% CI = 1.04-2.08). After CDI, patients remained at risk for gastrointestinal symptoms with CDI for up to two years. There is an important, long-term healthcare burden after CDI in this population.

The Open Insulin Project: A Case Study for 'Biohacked' Medicines.

New innovation ecosystems are emerging that challenge the complex intellectual property and regulatory landscape surrounding drug development in the United States (US). A prime example is an initiative known as the Open Insulin Project. The goal of the project is to sidestep patents and enable generic manufacturers to produce cheaper insulin. However, the US regulatory environment, not patent exclusivity, is the main barrier to insulin affordability. If the Open Insulin Project succeeds in releasing an open protocol for insulin manufacturing, follow-on work could enable a number of new insulin production ecosystems, including 'home-brewed' insulin. Regulators will need to consider how to proceed in a future where commercial pharmaceuticals remain unaffordable, but patients are empowered to produce drugs for their personal use.

Challenges constraining insulin access in Nepal-a country with no local insulin production.

Background: Nepal is facing an increasing burden of diabetes and relies almost entirely on insulin imported through India. Methods: We employed a modified version of the WHO/Health Action International standard survey to assess insulin availability and prices, along with qualitative interviews with insulin retailers (pharmacists) and wholesalers in the Kathmandu Valley, Nepal. Results: The mean availability of the two human insulins listed on the 2011 Nepal Essential Medicine List were 14.3% and 42.85% in the surveyed private- and public-sector pharmacies, respectively, compared with the WHO target of 80% availability. The median consumer price of human insulin cartridges, analogue insulin cartridges and pens was, respectively, 2.1, 4.6 and 5.3 times that of human insulin vials (US$5.54). The insulin cartridges made in India were less expensive (p<0.001) than those made elsewhere. The lowest-paid worker would need to spend between 3 and 17 days' wages to purchase a monthly insulin supply out of pocket. Conclusion: Insulin access is limited in Kathmandu owing to low availability and the highly unaffordable price. Insulin access could improve with the government exploring additional suppliers, pooling insulin tenders, auditing insulin utilization and developing independent prescribing guidelines. Furthermore, there is a need to educate physicians and develop a consensus statement on insulin initiation to curb the growing analogue use and promote rational use.

Growing concerns and controversies to Taiwan's National Health Insurance-what are the lessons from mainland China, South Korea and Singapore?

It has been over 20 years since Taiwan's implementation of its National Health Insurance (NHI) program. Under this program, the health insurance coverage rate has reached approximately 99% of the population. Despite guaranteeing the residents of Taiwan equal access regardless of socioeconomic status and background, critical problems and controversies persist, and they continue to challenge the NHI. We analyze the primary issues facing the NHI program with emphasis on financial and consumer behavioral aspects. Furthermore, we apply models from mainland China, South Korea and Singapore to discuss what Taiwan could learn from the systems employed by these countries to modify the NHI. Targeting the needs of the NHI, we have three policy recommendations: separating the NHI scheme into different target populations, strengthening the NHI referral system and regulating the access of overseas citizens to health services while in Taiwan. After two decades in existence, problems persist and there is a continuing need to improve Taiwan's NHI. Copyright © 2016 John Wiley & Sons, Ltd.

Trade in medicines and the public's health: a time series analysis of import disruptions during the 2015 India-Nepal border blockade.

BACKGROUND: Nepal was struck by devastating earthquakes in April-May 2015, followed by the India-Nepal border blockade later that year. METHODS: We used the United Nations Commodity Trade Statistics (UN Comtrade) database to analyse exports of various health commodities from India to Nepal from January 2011-September 2016. We used time-series regressions of trading volume vs. unit price to ask how well Nepal's trading history with India prior to the earthquake and blockade was able to predict unit prices of health commodities imported into Nepal during and after the earthquake and the blockade. Regression residuals were used to quantify the extent to which the blockade impacted the price of healthcare commodities crossing into Nepal. RESULTS: During the blockade period (September 2015-early February 2016), the volume of all retail medicines traded across the India-Nepal border was reduced by 46.5% compared to same months in 2014-2015. For medical dressings, large volumes were exported from India to Nepal during and shortly after the earthquakes (May-June 2015), but decreased soon thereafter. During the earthquake, the difference between observed and predicted values of unit price (residuals) for all commodities show no statistical outliers. However, during the border blockade, Nepal paid USD 22.3 million more for retail medicines than one would have predicted based on its prior trading history with India, enough to provide healthcare to nearly half of Kathmandu's citizens for 1 year. CONCLUSION: The India-Nepal blockade was a geopolitical natural experiment demonstrating how a land-locked country is vulnerable to the vagaries of its primary trading partner. Although short-lived, the blockade had an immediate impact on traded medicine volumes and prices, and provided a large opportunity cost with implications for public health.

Comparison of medicines management strategies in insurance schemes in middle-income countries: four case studies.

BACKGROUND: Many middle-income countries are scaling up health insurance schemes to provide financial protection and access to affordable medicines to poor and uninsured populations. Although there is a wealth of evidence on how high income countries with mature insurance schemes manage cost-effective use of medicines, there is limited evidence on the strategies used in middle-income countries. This paper compares the medicines management strategies that four insurance schemes in middle-income countries use to improve access and cost-effective use of medicines among beneficiaries. METHODS: We compare key strategies promoting cost-effective medicines use in the New Rural Cooperative Medical Scheme (NCMS) in China, National Health Insurance Scheme in Ghana, Jamkesmas in Indonesia and Seguro Popular in Mexico. Through the peer-reviewed and grey literature as of late 2013, we identified strategies that met our inclusion criteria as well as any evidence showing if, and/or how, these strategies affected medicines management. Stakeholders involved and affected by medicines coverage policies in these insurance schemes were asked to provide relevant documents describing the medicines related aspects of these insurance programs. We also asked them specifically to identify publications discussing the unintended consequences of the strategies implemented. RESULTS: Use of formularies, bulk procurement, standard treatment guidelines and separation of prescribing and dispensing were present in all four schemes. Also, increased transparency through publication of tender agreements and procurement prices was introduced in all four. Common strategies shared by three out of four schemes were medicine price negotiation or rebates, generic reference pricing, fixed salaries for prescribers, accredited preferred provider network, disease management programs, and monitoring of medicines purchases. Cost-sharing and payment for performance was rarely used. There was a lack of performance monitoring strategies in all schemes. CONCLUSIONS: Most of the strategies used in the insurance schemes focus on containing expenditure growth, including budget caps on pharmaceutical expenditures (Mexico) and ceiling prices on medicines (all four countries). There were few strategies targeting quality improvement as healthcare providers are mostly paid through fixed salaries, irrespective of the quality of their prescribing or the health outcomes actually achieved. Monitoring healthcare system performance has received little attention.

The global intellectual property ecosystem for insulin and its public health implications: an observational study.

BACKGROUND: Lack of access to insulin and poor health outcomes are issues for both low and high income countries. This has been accompanied by a shift from relatively inexpensive human insulin to its more expensive analogs, marketed by three to four main global players. Nonetheless, patent-based market exclusivities are beginning to expire there for the first generation insulin analogs. This paper adds a global dimension to information on the U.S. patent landscape for insulin by reviewing the patent status of insulins with emphasis on the situation outside the US and Europe. METHODS: Using the term "insulin", we searched for patents listed on the United States Food and Drug Administration's (USFDA) Orange Book and the Canadian Online Drug Product Database Online Query and its Patent Register. With this information, we expanded the search globally using the World Intellectual Property Organization (WIPO) PatentScope database, the European Patent Office's INPADOC database and various country-specific Patent Offices. RESULTS: Patent protected insulins marketed in the U.S. and other countries are facing an imminent patent-expiration "cliff' yet the three companies that dominate the global insulin market are continuing to file for patents in and outside the U.S, but very rarely in Africa. Only a few local producers in the so-called "pharmerging" markets (e.g., Brazil, India, China) are filing for global patent protection on their own insulins. There is moderate, but statistically significant association between patent filings and diabetes disease burden. CONCLUSIONS: The global market dominance by a few companies of analog over human insulin will likely continue even though patents on the current portfolio of insulin analogs will expire very soon. Multinationals are continuing to file for more insulin patents in the bigger markets with large disease burdens and a rapidly emerging middle class. Off-patent human insulins can effectively manage diabetes. A practical way forward would be find (potential) generic manufacturers globally and nudge them towards opportunities to diversify their national insulin markets with acceptable off-patent products for export.

Evaluation of the effects of a generic substitution policy implemented in Chile.

INTRODUCTION: Chile implemented a generic substitution policy in 2014 to improve access to medicines. This study aims to measure if the generic substitution policy had an effect on the sales volume and prices of referent and the branded generic products with demonstrated bioequivalence (BEQ) in the private pharmaceutical market. METHODS: The volume and total private sales of medicines sold at private sector retail outlets between November 2011 and October 2016 were considered in the analysis. We calculated the total number of daily defined doses (DDD) by adding up the number of DDDs of different presentations with the active pharmaceutical ingredient (API). We determined the ratio of the median prices of all BEQ per DDD presentations compared with the median price of the corresponding referent presentations per DDD in 2011 and 2016. Sixteen APIs representing 231 different conventional-release presentations were included in the analysis. RESULTS: Overall, the volume of sales of the referent products decreased over time after the intervention. However, this reduction was not mirrored by an increase in the corresponding branded generic BEQ volumes overall. In all cases, the median price per DDD of the referent was higher than its BEQ counterpart in 2011 and 2016. CONCLUSION: Since referent products are more costly than branded BEQ generic products, reducing their consumption-and increasing the BEQ availability-should improve access to medicines in Chile. However, this must be accompanied by promotion of BEQ products to ensure savings for consumers in the long term. Future research should focus on identifying facilitating and inhibiting factors of generic substitution.