SDG indicator 3.b.3 - an analysis of its robustness and challenges for measuring access to medicines for children.

BACKGROUND: Sustainable Development Goal (SDG) indicator 3.b.3 monitors progress in medicines' accessibility for adults and has significant limitations when applying to medicines for children. An adapted indicator methodology was developed to fill this gap, but no proof of its robustness exists. We provide this evidence through sensitivity analyses. METHODS: Data on availability and prices of child medicines from ten historical datasets were combined to create datasets for analysis: Dataset 1 (medicines selected at random) and Dataset 2 (preference given to available medicines, to better capture affordability of medicines). A base case scenario and univariate sensitivity analyses were performed to test critical components of the methodology, including the new variable of number of units needed for treatment (NUNT), disease burden (DB) weighting, and the National Poverty Line (NPL) limits. Additional analyses were run on a continuously smaller basket of medicines to explore the minimum number of medicines required. Mean facility scores for access were calculated and compared. RESULTS: The mean facility score for Dataset 1 and Dataset 2 within the base case scenario was 35.5% (range 8.0-58.8%) and 76.3% (range 57.2-90.6%). Different NUNT scenarios led to limited variations in mean facility scores of + 0.1% and -0.2%, or differences of + 4.4% and -2.1% at the more critical NPL of $5.50 (Dataset 1). For Dataset 2, variations to the NUNT generated differences of + 0.0% and -0.6%, at an NPL of $5.50 the differences were + 5.0 and -2.0%. Different approaches for weighting for DB induced considerable fluctuations of 9.0% and 11.2% respectively. Stable outcomes with less than 5% change in mean facility score were observed for a medicine basket down to 12 medicines. For smaller baskets, scores increased more rapidly with a widening range. CONCLUSION: This study has confirmed that the proposed adaptations to make SDG indicator 3.b.3 appropriate for children are robust, indicating that they could be an important addition to the official Global Indicator Framework. At least 12 child-appropriate medicines should be surveyed to obtain meaningful outcomes. General concerns that remain about the weighting of medicines for DB and the NPL should be considered at the 2025 planned review of this framework.

Mapping the Antimicrobial Supply Chain in Bangladesh: A Scoping-Review-Based Ecological Assessment Approach.

INTRODUCTION: Maintaining access to antimicrobials while preventing misuse is essential to combating the threat of antimicrobial resistance (AMR). The study objectives are to propose a framework of 16 indicators that can be used at the national level to assess the capacity to ensure access and curtail inappropriate use and to profile the antimicrobial supply chain for Bangladesh. METHODS: Using a framework based on a rational construct, we assessed the antimicrobial supply chain of Bangladesh, with a focus on key players and products using a scoping review to obtain and describe information on 16 indicators. With players, we mapped linkages, manufacturers' production capacity, and ownership, among others, and demand point characteristics-pharmacy and pharmacist density, pharmacy/medicine outlets dispersion, veterinary clinic/hospitals, veterinarians' density, product quality, and regulation. We assessed product characteristics including listing on the World Health Organization (WHO) Model Essential Medicines List (EML) and WHO Access, Watch, and Reserve (AWaRe) classification of the major (top 10) antibiotics for human use; the proportion of medically important antimicrobials (MIAs) in veterinary use; and pricing. Production capacity and price controls were used to assess access and listing on the WHO EML, AWaRe/MIA classification, and a calculated pharmacy-to-pharmacist ratio to assess use. RESULTS: Bangladesh has a high (98%) local antibiotic production capacity with pricing controls indicating the ability to ensure access. The presence of a high proportion of medicine outlets not under the control of pharmacists (4:1) and the high percentages of WHO Watch (54%) and MIAs (90%) of the major antibiotics are indicators of possible misuse. DISCUSSION: Most of the data used in the framework were publicly available. Bangladesh has the capacity to ensure access but needs to strengthen its ability to regulate the quality of antimicrobials and prevent their inappropriate use through antimicrobial stewardship at the community (medicine outlet) levels to check AMR. There may also be a need for more regulations on licensing of MIAs.

Tackling the blind spot of poor-quality medicines in Universal Health Coverage.

BACKGROUND: Universal Health Coverage (UHC) is challenged by the prevalence of poor-quality medicines, those that either do not meet required specifications (substandard) or are outrightly fraudulent (falsified), especially in Low- and Middle-Income Countries, LMICs. Whereas poor-quality medicines are a significant burden in these countries, medicine quality still remains a neglected component of UHC programs. This article describes key barriers to quality medicines and presents five select approaches leveraging the scale-up of UHC for medicine quality assurance. MAIN BODY: Barriers to medicine quality assurance, while numerous, are described in five key inter-related domains as: low political priority, weak regulatory systems capacity, poor access to accredited facilities and licensed outlets, medicine manufacturing and other supply-chain challenges, and lack of public awareness. Five select approaches for leveraging the scale-up of UHC for medicine quality assurance in LMICs are (1): political commitment (2) strengthening the capacity of regulatory authorities and investment in detection technologies as part of national security (3); licensing of medicines outlets and expanding pharmacovigilance (4); strengthening the supply-chain; and (5) public awareness and participation. CONCLUSIONS: Unchecked, poor-quality medicines can jeopardize UHC. National governments in LMICs need to prioritize medicine quality assurance through enforcing policies, regulatory strengthening and investments in technologies. Healthcare facilities and insurance schemes under UHC also play critical roles through incorporating medicine quality assurance into procurement practices and by promoting awareness among beneficiaries. Tackling medicine quality with a committed systems approach will enhance progress towards UHC implementation.

Pharmaceutical industry-led partnerships focused on addressing the global burden of non-communicable diseases: a review of Access Accelerated.

OBJECTIVE: In spite of the increasing number of global health partnerships led by biopharmaceutical companies, there is a paucity of information on the number, type, and role of partners. This paper aims to analyze partnerships carrying out company programs included in Access Accelerated, a new industry initiative, focused on addressing the global non-communicable disease burden. STUDY DESIGN: Document review and content analysis. METHODS: We extracted data on the number, type, and role of partners from 63 company programs reported into the Access Observatory, a public platform for reporting on access-to-medicines programs, in 2017. We did a descriptive analysis of the proportion of partners by sector, institution, and location. We used the Fischer's exact test to analyze the relationship between the program strategies, disease focus, and countries with the type of program partners. Based on our empirical findings, we developed a typology of program partnerships, according to which we categorized each of the 63 programs. RESULTS: Programs worked with three partners on average, the majority of which were local governmental or non-governmental organizations (70%). Most programs focused on health service strengthening (83%), community awareness and linkage to care (81%), and health service delivery (60%). Twenty-six of the 63 programs (41%) worked with the local Ministries of Health while 25 (40%) partnered with disease-specific organizations, 21 (33%) with hospitals, and 16 (25%) with academic institutions. Partnering with the Ministries of Health was significantly associated with the use of a health service strengthening program strategy (P = 0.02). Partnering with a hospital (P = 0.004) or private sector partner (P = 0.0009) was significantly associated with a program disease focus on cancer. Seventy-nine percent of the programs were solely funded by pharmaceutical companies. According to our program typology, 40 (63%) programs partnered directly or indirectly with multiple implementing organizations, which delivered the program directly to beneficiaries. CONCLUSION: Pharmaceutical companies play a leading role in funding Access Accelerated programs with local governmental or non-governmental organizations mainly involved in program implementation. A detailed and transparent reporting of the role of local stakeholders in agenda setting, planning, and coordination of programs is needed to ensure public trust and accountability of programs led by pharmaceutical companies. More research is needed to identify the partnerships that are particularly suitable to promote efficient implementation, evaluation, and reporting depending on the nature of the program and context.

A perspective on global access to insulin: a descriptive study of the market, trade flows and prices.

AIM: To describe the global insulin market. METHODS: Market intelligence data, United Nations Commodity Trade Statistics for insulin trade, the International Medical Products Price Guide for prices of human insulin and additional web searches were used as data sources. These sources were combined to gain further insight into possible links among market, trade flows and prices. Descriptive statistics and Spearman's rank order correlation were used for the analysis. RESULTS: A total of 34 insulin manufacturers were identified. Most countries and territories are reliant on a limited number of supplying countries. The overall median (interquartile range) government procurement price for a 10-ml, 100-IU/ml vial during the period 1996-2013 equivalent was US$4.3 (US$ 3.8-4.8), with median prices in Africa (US$ 4.7) and low- (US$ 6.9) and low- to middle- (US$ 4.7) income countries being higher over this period. The relationships between price and quantity of insulin (Spearman's r=0.046; P>0.1) and number of import links (Spearman's r=0.032; P>0.1) were weak. The links between price and percentage of total insulin from a country where a 'big three' manufacturer produces insulin (Spearman's r=0.294; P<0.05) and total insulin from the main import link (Spearman's r=-0.392; P<0.05) were stronger. CONCLUSIONS: This research shows the high variability of insulin prices and the reliance on a few sources, both companies and countries, for global supply. In addressing access to insulin, countries need to use existing price data to negotiate prices, and mechanisms need to be developed to foster competition and security of supply of insulin, given the limited number of truly global producers.

Access to asthma medicines at the household level in eight counties of Kenya.

BACKGROUND: It is estimated that about 4 million Kenyans, i.e., 10% of the country's population, have asthma. We aimed to evaluate access to asthma medicines at the household level in eight counties of Kenya, including factors associated with location of purchase. METHODS: Individuals with a diagnosis and prescription of asthma medicines were asked about the location of diagnosis, purchase of medicines, availability of medicines at home and costs of medicines per month. A logistic regression model explored the relationship between patient characteristics and the probability that the patient purchased asthma medicines at a public facility. RESULTS: Of 128 (15.2%) individuals with a diagnosis of asthma who were receiving treatment, only 57.0% had asthma medicines at home. The most frequently purchased asthma medicine was salbutamol, with one third of individuals taking it orally instead of by inhalation. The majority (55.4%) purchased asthma medicines at private pharmacies. Female patients and lower socio-economic status were predictors of purchasing asthma medicines at public facilities. CONCLUSIONS: The availability and affordability of asthma medicines remain significant barriers to access to care. Improving the availability and affordability of all asthma medicines in the public sector, including inhaled corticosteroids, offers the opportunity to reach vulnerable populations.

Analysing policy interventions to prohibit over-the-counter antibiotic sales in four Latin American countries.

OBJECTIVES: To describe and evaluate policies implemented in Chile, Colombia, Venezuela and Mexico (1995-2009) to prohibit antibiotic OTC sales and explore limitations in available data. METHODS: We searched and analysed legislation, grey literature and peer-reviewed publications on regulatory interventions and implementation strategies to enforce prohibition of OTC antibiotic sales. We also assessed the impact using private sector retail sales data of antibiotics studying changes in level and consumption trends before and after the policy change using segmented time series analysis. Finally, we assessed the completeness and data quality through an established checklist to test the suitability of the data for analysis of the interventions. RESULTS: Whereas Chile implemented a comprehensive package of interventions to accompany regulation changes, Colombia's reform was limited to the capital district and Venezuela's limited to only some antibiotics and without awareness campaigns. In Mexico, no enforcement was enacted. The data showed a differential effect of the intervention among the countries studied with a significant change in level of consumption in Chile (-5.56 DID) and in Colombia (-1.00DID). In Venezuela and Mexico, no significant change in level and slope was found. Changes in population coverage were identified as principal limitations of using sales data for evaluating the reform impact. CONCLUSION: Retail sales data can be useful when assessing policy impact but should be supplemented by other data sources such as public sector sales and prescription data. Implementing regulatory enforcement has shown some impact, but a sustainable, concerted approach will be needed to address OTC sales in the future.

Indicators of quality use of medicines in South-East Asian countries: a systematic review.

OBJECTIVES: To identify indicators of quality use of medicines used in South-East Asian region. METHODS: A systematic review was conducted searching MEDLINE, Embase and The International Network for Rational Use of Drugs (INRUD) and The World Health Organization (WHO) website. Original studies or reports carried out in the South-East Asian region, explicitly using indicators to measure quality use of medicines, and published between January 2000 and July 2011 were included. RESULTS: A total of 17 studies conducted in 7 of 11 countries in South-East Asia were included. WHO indicators focusing on general medication use in health facilities were most widely used (10 studies). Twelve studies used non-WHO indicators for measuring quality use of medicines in clinical areas (geriatrics and obstetrics) or specific diseases, such as diarrhoea and pneumonia. In five studies, WHO indicators were used along with non-WHO indicators. There was little information available about validity, reliability and feasibility of the non-WHO indicators. The majority of indicators measured process rather than structure or outcome. There were very few indicators addressing non-communicable diseases. CONCLUSIONS: A limited number of studies have been published explicitly using indicators of quality use of medicines across South-East Asia. Importantly, existing indicators need to be complemented with valid, reliable and feasible indicators related to non-communicable diseases, particularly those with a high financial burden to meet the current medical challenges in the region.

Safety and exposure of once-daily ritonavir-boosted atazanavir in HIV-infected pregnant women.

OBJECTIVE: There are limited antiretroviral options for use in the treatment of HIV infection during pregnancy. The purpose of this study was to assess the safety, efficacy and appropriate dosing regimen for ritonavir (RTV)-boosted atazanavir in HIV-1-infected pregnant women. METHODS: In this nonrandomized, open-label study, HIV-infected pregnant women were dosed with either 300/100 mg (n=20) or 400/100 mg (n=21) atazanavir/RTV once-daily (qd) in combination with zidovudine (300 mg) and lamivudine (150 mg) twice daily in the third trimester. Pharmacokinetic parameters [maximum observed plasma concentration (C(max) ), trough observed plasma concentration 24 hour post dose (C(min) ) and area under concentration-time curve in one dosing interval (AUC(τ) )] were determined and compared with historical values (300/100 mg atazanavir/RTV) for HIV-infected nonpregnant adults (n=23). RESULTS: At or before delivery, all mothers achieved HIV RNA <50 HIV-1 RNA copies/mL and all infants were HIV DNA negative at 6 months of age. The third trimester AUC(τ) for atazanavir/RTV 300/100 mg was 21% lower than historical data, but the C(min) values were comparable. The C(min) value for atazanavir/RTV 400/100 mg was 39% higher than the C(min) for atazanavir/RTV 300/100 mg in historical controls, but the AUC(τ) values were comparable. Twice as many patients in the 400/100 mg group (62%) had an increase in total bilirubin (>2.5 times the upper limit of normal) as in the 300/100 mg group (30%). Atazanavir (ATV) was well tolerated with no unanticipated adverse events. CONCLUSIONS: In this study, use of atazanavir/RTV 300/100 mg qd produced C(min) comparable to historical data in nonpregnant HIV-infected adults. When used in combination with zidovudine/lamivudine, it suppressed HIV RNA in all mothers and prevented mother-to-child transmission of HIV-1 infection. During pregnancy, the pharmacokinetics, safety and efficacy demonstrated that a dose adjustment is not required for ATV.