Improving malaria case management with artemisinin-based combination therapies and malaria rapid diagnostic tests in private medicine retail outlets in sub-Saharan Africa: A systematic review.

Private medicine retailers (PMRs) such as pharmacies and drug stores account for a substantial share of treatment-seeking for fever and malaria, but there are widespread concerns about quality of care, including inadequate access to malaria rapid diagnostic tests (RDTs) and artemisinin-based combination therapies (ACTs). This review synthesizes evidence on the effectiveness of interventions to improve malaria case management in PMRs in sub-Saharan Africa (PROSPERO #2021:CRD42021253564). We included quantitative studies evaluating interventions supporting RDT and/or ACT sales by PMR staff, with a historical or contemporaneous control group, and outcomes related to care received. We searched Medline Ovid, Embase Ovid, Global Health Ovid, Econlit Ovid and the Cochrane Library; unpublished studies were identified by contacting key informants. We conducted a narrative synthesis by intervention category. We included 41 papers, relating to 34 studies. There was strong evidence that small and large-scale ACT subsidy programmes (without RDTs) increased the market share of quality-assured ACT in PMRs, including among rural and poorer groups, with increases of over 30 percentage points in most settings. Interventions to introduce or enhance RDT use in PMRs led to RDT uptake among febrile clients of over two-thirds and dispensing according to RDT result of over three quarters, though some studies had much poorer results. Introducing Integrated Community Case Management (iCCM) was also effective in improving malaria case management. However, there were no eligible studies on RDT or iCCM implementation at large scale. There was limited evidence that PMR accreditation (without RDTs) increased ACT uptake. Key evidence gaps include evaluations of RDTs and iCCM at large scale, evaluations of interventions including use of digital technologies, and robust studies of accreditation and other broader PMR interventions.

"Caught in Each Other's Traps": Factors Perpetuating Incentive-Linked Prescribing Deals Between Physicians and the Pharmaceutical Industry.

BACKGROUND: Despite known adverse impacts on patients and health systems, "incentive-linked prescribing," which describes the prescribing of medicines that result in personal benefits for the prescriber, remains a widespread and hidden impediment to quality of healthcare. We investigated factors perpetuating incentive-linked prescribing among primary care physicians in for-profit practices (referred to as private doctors - PDs), using Pakistan as a case study. METHODS: Our mixed-methods study synthesised insights from a survey of 419 systematically sampled PDs and 68 semi-structured interviews with PDs (n=28), pharmaceutical sales representatives (SRs) (n=12), and provincial and national policy actors (n=28). For the survey, we built a verified database of all registered PDs within Karachi, Pakistan's most populous city, administered an electronic questionnaire in-person and descriptively analysed the data. Semi-structured interviews incorporated a vignette-based exercise and data was analysed using an interpretive approach. RESULTS: Our survey showed that 90% of PDs met pharmaceutical SRs weekly. Three interlinked factors perpetuating incentive-linked prescribing we identified were: gaps in understanding of conflicts of interest and loss of values among doctors; financial pressures on doctors operating in a (largely) privately financed health-system, exacerbated by competition with unqualified healthcare providers; and aggressive incentivisation by pharmaceutical companies, linked to low political will to regulate an over-saturated pharmaceutical market. CONCLUSION: Regular interactions between pharmaceutical companies and PDs are normalised in our study setting. Progress on regulating these is hindered by the substantial role of incentive-linked prescribing in the financial success of physicians and pharmaceutical industry employees. A first step towards addressing the entrenchment of incentive-linked prescribing may be to reduce opposition to restrictions on incentivisation of physicians from stakeholders within the pharmaceutical industry, physicians themselves, and policy-makers concerned about curtailing growth of the pharmaceutical industry.

Management Practices and Quality of Care: Evidence from the Private Health Care Sector in Tanzania.

We measure the adoption of management practices in over 220 private for-profit and non-profit health facilities in 64 districts across Tanzania and link these data to process quality-of-care metrics, assessed using undercover standardised patients and clinical observations. We find that better managed health facilities are more likely to provide correct treatment in accordance with national treatment guidelines, adhere to a checklist of essential questions and examinations, and comply with infection prevention and control practices. Moving from the 10th to the 90th percentile in the management practice score is associated with a 48% increase in correct treatment. We then leverage a large-scale field experiment of an internationally recognised management support intervention in which health facilities are assessed against comprehensive standards, given an individually tailored quality improvement plan and supported through training and mentoring visits. We find zero to small effects on management scores, suggesting that improving management practices in this setting may be challenging.

The nature, drivers and equity consequences of informal payments for maternal and child health care in primary health centres in Enugu, Nigeria.

In Nigeria, most basic maternal and child health services in public primary health-care facilities should be either free of charge or subsidized. In practice, additional informal payments made in cash or in kind are common. We examined the nature, drivers and equity consequences of informal payments in primary health centres (PHC) in Enugu State. We used three interlinked qualitative methods: participant observation in six PHC facilities and two local government area (LGA) headquarters; in-depth interviews with frontline health workers (n = 19), managers (n = 4) and policy makers (n = 10); and focus group discussions (n = 2) with female service users. Data were analysed thematically using NVivo 12. Across all groups, informal payments were described as routine for immunization, deliveries, family planning consultations and birth certificate registration. Health workers, managers and policy makers identified limited supervision, insufficient financing of facilities, and lack of receipts for formal payments as enabling this practice. Informal payments were seen by managers and health workers as a mechanism to generate discretionary revenue to cover operational costs of the facility but, in practice, were frequently taken as extra income by health workers. Health workers rationalized informal payments as being of small value, and not a burden to users. However, informal payments were reported to be inequitable and exclusionary. Although they tended to be lower in rural PHCs than in wealthier urban facilities, participant observation revealed how, within a PHC, the lowest earners paid the same as others and were often left unattended if they failed to pay. Some female patients reported that extra payments excluded them from services, driving them to seek help from retail outlets or unlicensed health providers. As a result, informal payments reduced equity of access to essential services. Targeted policies are needed to improve financial risk protection for the poorest groups and address drivers of informal payments and unfairness in the health system.

Engaging the private sector to deliver quality maternal and newborn health services for universal health coverage: lessons from policy dialogues.

The private health sector is becoming increasingly important in discussions on improving the quality of care for maternal and newborn health (MNH). Yet information rarely addresses what engaging the private sector for MNH means and how to do it. In 2019, the Network for Improving Quality of Care for Maternal, Newborn and Child Health (the Network) initiated exploratory research to better understand how to ensure that the private sector delivers quality care and what the public sector must do to facilitate and sustain this process. This article details the approach and lessons learnt from two Network countries, Ghana and Nigeria, where teams explored the mechanisms for engaging the private sector in delivering MNH services with quality. The situational analyses in Ghana and Nigeria revealed challenges in engaging the private sector, including lack of accurate data, mistrust and an unlevel playing field. Challenging market conditions hindered a greater private sector role in delivering quality MNH services. Based on these analyses, participants at multistakeholder workshops recommended actions addressing policy/administration, regulation and service delivery. The findings from this research help strengthen the evidence base on engaging the private sector to deliver quality MNH services and show that this likely requires engagement with broader health systems factors. In recognition of this need for a balanced approach and the new WHO private sector strategy, the WHO has updated the tools and process for countries interested in conducting this research. The Nigerian Ministry of Health is stewarding additional policy dialogues to further engage the private sector.

Does increased provider effort improve quality of care? Evidence from a standardised patient study on correct and unnecessary treatment.

BACKGROUND: Poor quality of care, including overprovision (unnecessary care) is a global health concern. Greater provider effort has been shown to increase the likelihood of correct treatment, but its relationship with overprovision is less clear. Providers who make more effort may give more treatment overall, both correct and unnecessary, or may have lower rates of overprovision; we test which is true in the Tanzanian private health sector. METHODS: Standardised patients visited 227 private-for-profit and faith-based facilities in Tanzania, presenting with symptoms of asthma and TB. They recorded history questions asked and physical examinations carried out by the provider, as well as laboratory tests ordered, treatments prescribed, and fees paid. A measure of provider effort was constructed on the basis of a checklist of recommended history taking questions and physical exams. RESULTS: 15% of SPs received the correct care for their condition and 74% received unnecessary care. Increased provider effort was associated with increased likelihood of correct care, and decreased likelihood of giving unnecessary care. Providers who made more effort charged higher fees, through the mechanism of higher consultation fees, rather than increased fees for lab tests and drugs. CONCLUSION: Providers who made more effort were more likely to treat patients correctly. A novel finding of this study is that they were also less likely to provide unnecessary care, suggesting it is not simply a case of some providers doing "more of everything", but that those who do more in the consultation give more targeted care.

How much does effective health facility inspection cost? An analysis of the economic costs of Kenya's Joint Health Inspection innovations.

BACKGROUND: In most low- and middle-income countries, health facility regulation is fragmented, ineffective and under-resourced. The Kenyan Government piloted an innovative regulatory regime involving Joint Health Inspections (JHI) which synthesized requirements across multiple regulatory agencies; increased inspection frequency; digitized inspection tools; and introduced public display of regulatory results. The pilot significantly improved regulatory compliance. We calculated the costs of the development and implementation of the JHI pilot and modelled the costs of national scale-up in Kenya. METHODS: We calculated the economic costs of three phases: JHI checklist development, start-up activities, and first year of implementation, from the providers' perspective in three pilot counties. Data collection involved extraction from expenditure records and key informant interviews. The annualized costs of JHI were calculated by adding annualized development and start-up costs to annual implementation costs. National level scale-up costs were also modelled and compared to those of current standard inspections. RESULTS: The total economic cost of the JHI pilot was USD 1,125,600 (2017 USD), with the development phase accounting for 19%, start-up 43% and the first year of implementation 38%. The annualized economic cost was USD 519,287, equivalent to USD 206 per health facility visit and USD 311 per inspection completed. Scale up to the national level, while replacing international advisors with local staff, was estimated to cost approximately USD 4,823,728, equivalent to USD 103 per health facility visit and USD 155 per inspection completed. This compares to an estimated USD 86,997 per year (USD 113 per inspection completed) spent on a limited number of inspections prior to JHI. CONCLUSION: Information on costs is essential to consider affordability and value for money of regulatory interventions. This is the first study we are aware of costing health facility inspections in sub-Saharan Africa. It has informed debates on appropriate inspection design and potential efficiency gains. It will also serve as an important benchmark for future studies, and a key input into cost-effectiveness analyses.

Healthcare clinic and pharmacy chains in Kenya and Nigeria: A qualitative exploration of the opportunities and risks they present for healthcare regulatory systems.

BACKGROUND: Regulating fragmented healthcare markets is a major challenge in low- and middle-income countries. Although a recent transformation towards consolidation could improve regulatory efficiency, there are concerns over risks to client safety and market functioning. We investigated market consolidation through the emergence of clinic and pharmacy chains in Kenya and Nigeria and explored resultant regulatory opportunities and risks. METHODS: The study was conducted in Nairobi Kenya and Abuja Nigeria. Data were collected through document reviews and 26 interviews with chain operators, professional associations and regulators between September and December 2018. A thematic analysis was conducted. RESULTS: We characterised two broad types of chains: organic chains that started as single business locations and expanded gradually, and investor-driven chains that expanded rapidly following external capital injection. In both countries, chains and independents were regulated similarly, with regulators failing to both capitalize on opportunities and guard against risks. For instance, chains' brand visibility and centralised management systems made them easier to regulate and more suitable for self-regulation. On the other hand, chains were perceived to pose the risks of market dominance, commercialisation of healthcare, and regulatory capture. CONCLUSION: As healthcare chains expand, regulators should build on opportunities presented and guard against emerging risks.

Pushy Patients Or Pushy Providers? Effect Of Patient Knowledge On Antibiotic Prescribing In Tanzania.

Antimicrobial resistance is one of the most serious threats to global health, but little progress has been made in reversing its spread. Inappropriate use of antibiotics in humans is a major driver of antimicrobial resistance, and rates are high and growing in lower- and middle-income countries. Antibiotics are thought to be subject to supplier-induced demand, whereby providers prescribe them to patients who do not know they are unnecessary. We conducted a randomized field experiment in 227 private health facilities in Tanzania, with standardized patients presenting uncomplicated upper respiratory tract infection symptoms. Standardized patients were randomly assigned to express knowledge (informed) or not (uninformed) that antibiotics were not required to treat them. There was a very high rate of inappropriate antibiotic prescription, with 86.0 percent of informed standardized patients and 94.8 percent of uninformed standardized patients prescribed an antibiotic, for an adjusted difference of 7.8 percentage points between the groups. This small effect suggests that broader health systems factors are at play and that interventions should be aimed at systems, health facilities, and providers.

Using donor funding to catalyse investment in malaria prevention in Ghana: an analysis of the potential impact on public and private sector expenditure.

BACKGROUND: An estimated 1.5 billion malaria cases and 7.6 million malaria deaths have been averted globally since 2000; long-lasting insecticidal nets (LLINs) have contributed an estimated 68% of this reduction. Insufficient funding at the international and domestic levels poses a significant threat to future progress and there is growing emphasis on the need for enhanced domestic resource mobilization. The Private Sector Malaria Prevention (PSMP) project was a 3-year intervention to catalyse private sector investment in malaria prevention in Ghana. METHODS: To assess value for money of the intervention, non-donor expenditure in the 5 years post-project catalysed by the initial donor investment was predicted. Non-donor expenditure catalysed by this investment included: workplace partner costs of malaria prevention activities; household costs in purchasing LLINs from retail outlets; domestic resource mobilization (public sector financing and private investors). Annual ratios of projected non-donor expenditure to annualized donor costs were calculated for the 5 years post-project. Alternative scenarios were constructed to explore uncertainty around future consequences of the intervention. RESULTS: The total donor financial cost of the 3-year PSMP project was USD 4,418,996. The average annual economic donor cost per LLIN distributed through retail sector and workplace partners was USD 21.17 and USD 7.55, respectively. Taking a 5-year post-project time horizon, the annualized donor investment costs were USD 735,805. In the best-case scenario, each USD of annualized donor investment led to USD 4.82 in annual projected non-donor expenditure by the fifth-year post-project. With increasingly conservative assumptions around the project consequences, this ratio decreased to 3.58, 2.16, 1.07 and 0.93 in the "very good", "good", "poor" and "worst" case scenarios, respectively. This suggests that in all but the worst-case scenario, donor investment would be exceeded by the non-donor expenditure it catalysed. CONCLUSIONS: The unit cost per net delivered was high, reflecting considerable initial investment costs and relatively low volumes of LLINs sold during the short duration of the project. However, taking a longer time horizon and broader perspective on the consequences of this complex catalytic intervention suggests that considerable domestic resources for malaria control could be mobilized, exceeding the value of the initial donor investment.

Availability, Prices and Affordability of Antibiotics Stocked by Informal Providers in Rural India: A Cross-Sectional Survey.

Providers without formal training deliver healthcare and antibiotics across rural India, but little is known about the antibiotics that they stock. We conducted a cross-sectional survey of such informal providers (IPs) in two districts of West Bengal, and assessed the availability of the antibiotics, as well as their sales volumes, retail prices, percentage markups for IPs and affordability. Of the 196 IPs that stocked antibiotics, 85% stocked tablets, 74% stocked syrups/suspensions/drops and 18% stocked injections. Across all the IPs, 42 antibiotic active ingredients were stocked, which comprised 278 branded generics from 74 manufacturers. The top five active ingredients that were stocked were amoxicillin potassium clavulanate (52% of the IPs), cefixime (39%), amoxicillin (33%), azithromycin (25%) and ciprofloxacin (21%). By the WHO's AWaRe classification, 71% of the IPs stocked an ACCESS antibiotic and 84% stocked a WATCH antibiotic. The median prices were in line with the government ceiling prices, but with substantial variation between the lowest and highest priced brands. The most affordable among the top five tablets were ciprofloxacin, azithromycin, cefixime and amoxicillin (US$ 0.8, 0.9, 1.9 and 1.9 per course), and the most affordable among the syrups/suspensions/drops were azithromycin and ofloxacin (US$ 1.7 and 4.5 per course, respectively), which are mostly WATCH antibiotics. IPs are a key source of healthcare and antibiotics in rural communities; practical interventions that target IPs need to balance restricting WATCH antibiotics and expanding the basket of affordable ACCESS antibiotics.

Cheaper Medicines for the Better Off? A Comparison of Medicine Prices and Client Socioeconomic Status Between Chain and Independent Retail Pharmacies in Urban India.

BACKGROUND: The growth of chain pharmacies in India, and other low- and middle-income countries (LMICs), is challenging the status quo of pharmacy retail markets which have historically been dominated by independent pharmacies. This raises the question of whether such organisations will have a positive impact on affordability and access to medicines. METHODS: This paper draws on a standardised patient (SP) survey to measure the prices of medicines and expenditure on consultations for two tracer conditions (suspected tuberculosis [TB] in an adult and diarrhoea in an absent child) at a random sample of 230 chain and independent pharmacies in Bengaluru. Asset data were collected from 808 exit interviews with pharmacy customers to determine socioeconomic profiles of clients. Results: Chain pharmacies were found to provide lower priced medicines for patients seeking care for diarrhoea and TB, with expenditure also lower for diarrhoea patients, compared to independent pharmacies. This was seemingly driven by lower prices rather than number of medicines dispensed or prescribing habits. Despite the availability of cheaper medicines, chains served wealthier clients, compared to independent pharmacies. CONCLUSION: The findings indicate the potential for chains to contribute to improving medicine affordability as they expand. However, any attempt to leverage this organisational model for public health good would need to take account of the current client-mix of these pharmacies and be accompanied by appropriate regulatory constraints in order to realise the potential benefits for poorer groups.

What Lies Behind Successful Regulation? A Qualitative Evaluation of Pilot Implementation of Kenya's Health Facility Inspection Reforms.

BACKGROUND: Health facility regulation in low- and middle-income countries (LMICs) is generally weak, with potentially serious consequences for safety and quality. Innovative regulatory reforms were piloted in three Kenyan counties including: a Joint Health Inspection Checklist (JHIC) synthesizing requirements across multiple regulatory agencies; increased inspection frequency; allocating facilities to compliance categories which determined warnings, sanctions and/or time to re-inspection; and public display of regulatory results. The reforms substantially increased inspection scores compared with control facilities. We developed lessons for future regulatory policy from this pilot by identifying key factors that facilitated or hindered its implementation. METHODS: We conducted a qualitative study to understand views and experiences of actors involved in the one-year pilot. We interviewed 77 purposively selected staff from the national, county and facility levels. Data were analyzed using the framework approach, identifying facilitating/hindering factors at the facility, inspection system, and health system levels. RESULTS: The joint health inspections (JHIs) were generally viewed as fair, objective and transparent, which enhanced their perceived legitimacy. Interactions with inspectors were described as friendly and supportive, in contrast to the punitive culture of previous inspections when bribery had been common. Inspector training and use of an electronic checklist were strongly praised. However, practical challenges with transport, route planning and budgets highlighted the critical nature of strong logistical management. The effectiveness of inspection in improving compliance was hampered by limitations in related systems, particularly facility licensing, enforcement of closures and, in the public sector, control of funds. However, an inclusive reform development process had led to high buy-in across regulatory agencies which was key to the system's success. CONCLUSION: Effective facility inspection involves more than "hardware" such as checklists, protocols and training. Cultural, relational and institutional "software" are also crucial for legitimacy, feasibility of implementation and enforceability, and should be carefully integrated into regulatory reforms.

Poor quality for the poor? A study of inequalities in service readiness and provider knowledge in Indonesian primary health care facilities.

BACKGROUND: For many low and middle-income countries poor quality health care is now responsible for a greater number of deaths than insufficient access to care. This has in turn raised concerns around the distribution of quality of care in LMICs: do the poor have access to lower quality health care compared to the rich? The aim of this study is to investigate the extent of inequalities in the availability of quality health services across the Indonesian health system with a particular focus on differences between care delivered in the public and private sectors. METHODS: Using the Indonesian Family Life Survey (wave 5, 2015), 15,877 households in 312 communities were linked with a representative sample of both public and private health facilities available in the same communities. Quality of health facilities was assessed using both a facility service readiness score and a knowledge score constructed using clinical vignettes. Ordinary least squares regression models were used to investigate the determinants of quality in public and private health facilities. RESULTS: In both sectors, inequalities in both quality scores existed between major islands. In public facilities, inequalities in readiness scores persisted between rural and urban areas, and to a lesser extent between rich and poor communities. CONCLUSION: In order to reach the ambitious stated goal of reaching Universal Health Coverage in Indonesia, priority should be given to redressing current inequalities in the quality of care.

Effect of a multifaceted intervention to improve clinical quality of care through stepwise certification (SafeCare) in health-care facilities in Tanzania: a cluster-randomised controlled trial.

BACKGROUND: Quality of care is consistently shown to be inadequate in health-care settings in many low-income and middle-income countries, including in private facilities, which are rapidly growing in number but often do not have effective quality stewardship mechanisms. The SafeCare programme aims to address this gap in quality of care, using a standards-based approach adapted to low-resource settings, involving assessments, mentoring, training, and access to loans, to improve clinical quality and facility business performance. We assessed the effect of the SafeCare programme on quality of patient care in faith-based and private for-profit facilities in Tanzania. METHODS: In this cluster-randomised controlled trial, health facilities were eligible if they were dispensaries, health centres, or hospitals in the faith-based or private for-profit sectors in Tanzania. We randomly assigned facilities (1:1) using computer-generated stratified randomisation to receive the full SafeCare package (intervention) or an assessment only (control). Implementing staff and participants were masked to outcome measurement and the primary outcomes were measured by fieldworkers who had no knowledge of the study group allocation. The primary outcomes were health worker compliance with infection prevention and control (IPC) practices as measured by observation of provider-patient interactions, and correct case management of undercover standardised patients at endline (after a minimum of 18 months). Analyses were by modified intention to treat. The trial is registered with ISRCTN, ISRCTN93644888. FINDINGS: Between March 7 and Nov 30, 2016, we enrolled and randomly assigned 237 health facilities to the intervention (n=118) or control (n=119). Nine facilities (seven intervention facilities and two control facilities) closed during the trial and were not included in the analysis. We observed 29 608 IPC indications in 5425 provider-patient interactions between Feb 7 and April 5, 2018. Health facilities received visits from 909 standardised patients between May 3 and June 12, 2018. Intervention facilities had a 4·4 percentage point (95% CI 0·9-7·7; p=0.015) higher mean SafeCare standards assessment score at endline than control facilities. However, there was no evidence of a difference in clinical quality between intervention and control groups at endline. Compliance with IPC practices was observed in 8181 (56·9%) of 14 366 indications in intervention facilities and 8336 (54·7%) of 15 242 indications in control facilities (absolute difference 2·2 percentage points, 95% CI -0·2 to -4·7; p=0·071). Correct management occurred in 120 (27·0%) of 444 standardised patients in the intervention group and in 136 (29·2%) of 465 in the control group (absolute difference -2·8 percentage points, 95% CI -8·6 to -3·1; p=0·36). INTERPRETATION: SafeCare did not improve clinical quality as assessed by compliance with IPC practices and correct case management. The absence of effect on clinical quality could reflect a combination of insufficient intervention intensity, insufficient links between structural quality and care processes, scarcity of resources for quality improvement, and inadequate financial and regulatory incentives for improvement. FUNDING: UK Health Systems Research Initiative (Medical Research Council, Economic and Social Research Council, UK Department for International Development, Global Challenges Research Fund, and Wellcome Trust).

Does subsidizing the private for-profit sector benefit the poor? Evidence from national antimalarial subsidies in Nigeria and Uganda.

Subsidising quality-assured artemisinin combination therapies (QAACTs) for distribution in the for-profit sector is a controversial strategy for improving access. The Affordable Medicines Facility-malaria (AMFm) was the largest initiative of this kind. We assessed the equity of AMFm in two ways using nationally representative household survey data on care seeking for children from Nigeria and Uganda. First, the delivery of subsidized drugs through the for-profit sector via AMFm was compared with two alternative mechanisms: subsidized delivery in public health facilities and unsubsidized delivery in the for-profit sector. Second, we developed a novel extension of benefit incidence analysis (BIA) methods based on the concept of pass-through, and applied them to Uganda. In Nigeria, the use of subsidized QAACTs from both public health facilities and for-profit outlets was concentrated among the rich, while in Uganda, the use of QAACTs from both sources was concentrated among the poor. Similarly, the BIA of AMFm found that the intervention was pro-poor in Uganda. Unsubsidized antimalarials from for-profit outlets were distributed equally across wealth quintiles in both countries. Private sector subsidies may have a role in bolstering access to effective malaria treatments, including among the poor, but the equity impact of subsidies may depend on context.

When technology precedes regulation: the challenges and opportunities of e-pharmacy in low-income and middle-income countries.

The recent growth of medicine sales online represents a major disruption to pharmacy markets, with COVID-19 encouraging this trend further. While e-pharmacy businesses were initially the preserve of high-income countries, in the past decade they have been growing rapidly in low-income and middle-income countries (LMICs). Public health concerns associated with e-pharmacy include the sale of prescription-only medicines without a prescription and the sale of substandard and falsified medicines. There are also non-health-related risks such as consumer fraud and lack of data privacy. However, e-pharmacy may also have the potential to improve access to medicines. Drawing on existing literature and a set of key informant interviews in Kenya, Nigeria and India, we examine the e-pharmacy regulatory systems in LMICs. None of the study countries had yet enacted a regulatory framework specific to e-pharmacy. Key regulatory challenges included the lack of consensus on regulatory models, lack of regulatory capacity, regulating sales across borders and risks of over-regulation. However, e-pharmacy also presents opportunities to enhance medicine regulation-through consolidation in the sector, and the traceability and transparency that online records offer. The regulatory process needs to be adapted to keep pace with this dynamic landscape and exploit these possibilities. This will require exploration of a range of innovative regulatory options, collaboration with larger, more compliant businesses, and engagement with global regulatory bodies. A key first step must be ensuring that national regulators are equipped with the necessary awareness and technical expertise to actively oversee this e-pharmacy activity.

How much healthcare is wasted? A cross-sectional study of outpatient overprovision in private-for-profit and faith-based health facilities in Tanzania.

Overprovision-healthcare whose harm exceeds its benefit-is of increasing concern in low- and middle-income countries, where the growth of the private-for-profit sector may amplify incentives for providing unnecessary care, and achieving universal health coverage will require efficient resource use. Measurement of overprovision has conceptual and practical challenges. We present a framework to conceptualize and measure overprovision, comparing for-profit and not-for-profit private outpatient facilities across 18 of mainland Tanzania's 22 regions. We developed a novel conceptualization of three harms of overprovision: economic (waste of resources), public health (unnecessary use of antimicrobial agents risking development of resistant organisms) and clinical (high risk of harm to individual patients). Standardized patients (SPs) visited 227 health facilities (99 for-profit and 128 not-for-profit) between May 3 and June 12, 2018, completing 909 visits and presenting 4 cases: asthma, non-malarial febrile illness, tuberculosis and upper respiratory tract infection. Tests and treatments prescribed were categorized as necessary or unnecessary, and unnecessary care was classified by type of harm(s). Fifty-three percent of 1995 drugs prescribed and 43% of 891 tests ordered were unnecessary. At the patient-visit level, 81% of SPs received unnecessary care, 67% received care harmful to public health (prescription of unnecessary antibiotics or antimalarials) and 6% received clinically harmful care. Thirteen percent of SPs were prescribed an antibiotic defined by WHO as 'Watch' (high priority for antimicrobial stewardship). Although overprovision was common in all sectors and geographical regions, clinically harmful care was more likely in for-profit than faith-based facilities and less common in urban than rural areas. Overprovision was widespread in both for-profit and not-for-profit facilities, suggesting considerable waste in the private sector, not solely driven by profit. Unnecessary antibiotic or antimalarial prescriptions are of concern for the development of antimicrobial resistance. Option for policymakers to address overprovision includes the use of strategic purchasing arrangements, provider training and patient education.

What are the challenges for antibiotic stewardship at the community level? An analysis of the drivers of antibiotic provision by informal healthcare providers in rural India.

In many low- and middle-income countries, providers without formal training are an important source of antibiotics, but may provide these inappropriately, contributing to the rising burden of drug resistant infections. Informal providers (IPs) who practise allopathic medicine are part of India's pluralistic health system legacy. They outnumber formal providers but operate in a policy environment of unclear legitimacy, creating unique challenges for antibiotic stewardship. Using a systems approach we analysed the multiple intrinsic (provider specific) and extrinsic (community, health and regulatory system and pharmaceutical industry) drivers of antibiotic provision by IPs in rural West Bengal, to inform the design of community stewardship interventions. We surveyed 291 IPs in randomly selected village clusters in two contrasting districts and conducted in-depth interviews with 30 IPs and 17 key informants including pharmaceutical sales representatives, managers and wholesalers/retailers; medically qualified private and public doctors and health and regulatory officials. Eight focus group discussions were conducted with community members. We found a mosaic or bricolage of informal practices conducted by IPs, qualified doctors and industry stakeholders that sustained private enterprise and supplemented the weak public health sector. IPs' intrinsic drivers included misconceptions about the therapeutic necessity of antibiotics, and direct and indirect economic benefits, though antibiotics were not the most profitable category of drug sales. Private doctors were a key source of IPs' learning, often in exchange for referrals. IPs constituted a substantial market for local and global pharmaceutical companies that adopted aggressive business strategies to exploit less-saturated rural markets. Paradoxically, the top-down nature of regulations produced a regulatory impasse wherein regulators were reluctant to enforce heavy sanctions for illegal sales, fearing an adverse impact on rural healthcare, but could not implement enabling strategies to improve antibiotic provision due to legal barriers. We discuss the implications for a multi-stakeholder antibiotic stewardship strategy in this setting.