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Substandard and falsified medications are a major threat to public health, directly increasing the risk of treatment failure, antimicrobial resistance, morbidity, mortality and health expenditures. While antimalarial medicines are one of the most common to be of poor quality in low- and middle-income countries, their distributional impact has not been examined. This study assessed the health equity impact of substandard and falsified antimalarials among children under five in Uganda. Using a probabilistic agent-based model of paediatric malaria infection (Substandard and Falsified Antimalarial Research Impact, SAFARI model), we examine the present day distribution of the burden of poor-quality antimalarials by socio-economic status and urban/rural settings, and simulate supply chain, policy and patient education interventions. Patients incur US$26.1 million (7.8%) of the estimated total annual economic burden of substandard and falsified antimalarials, including $2.3 million (9.1%) in direct costs and $23.8 million (7.7%) in productivity losses due to early death. Poor-quality antimalarials annually cost $2.9 million to the government. The burden of the health and economic impact of malaria and poor-quality antimalarials predominantly rests on the poor (concentration index -0.28) and rural populations (98%). The number of deaths among the poorest wealth quintile due to substandard and falsified antimalarials was 12.7 times that of the wealthiest quintile, and the poor paid 12.1 times as much per person in out-of-pocket payments. Rural populations experienced 97.9% of the deaths due to poor-quality antimalarials, and paid 10.7 times as much annually in out-of-pocket expenses compared with urban populations. Our simulations demonstrated that interventions to improve medicine quality could have the greatest impact at reducing inequities, and improving adherence to antimalarials could have the largest economic impact. Substandard and falsified antimalarials have a significant health and economic impact, with greater burden of deaths, disability and costs on poor and rural populations, contributing to health inequities in Uganda., (© The Author(s) 2019. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.)

Introduction: Substandard and falsified medications pose significant risks to global health. Nearly one in five antimalarials circulating in low- and middle-income countries are substandard or falsified. We assessed the health and economic impact of substandard and falsified antimalarials on children under five in Nigeria, where malaria is endemic and poor-quality medications are commonplace., Methods: We developed a dynamic agent-based SAFARI (Substandard and Falsified Antimalarial Research Impact) model to capture the impact of antimalarial use in Nigeria. The model simulated children with background characteristics, malaria infections, patient care-seeking, disease progression, treatment outcomes, and incurred costs. Using scenario analyses, we simulated the impact of substandard and falsified medicines, antimalarial resistance, as well as possible interventions to improve the quality of treatment, reduce stock-outs, and educate caregivers about antimalarial quality., Results: We estimated that poor quality antimalarials are responsible for 12,300 deaths and $892 million ($890-$893 million) in costs annually in Nigeria. If antimalarial resistance develops, we simulated that current costs of malaria could increase by $839 million (11% increase, $837-$841 million). The northern regions of Nigeria have a greater burden as compared to the southern regions, with 9,700 deaths and $698 million ($697-$700 million) in total economic losses annually due to substandard and falsified antimalarials. Furthermore, our scenario analyses demonstrated that possible interventions-such as removing stock-outs in all facilities ($1.11 billion), having only ACTs available for treatment ($594 million), and 20% more patients seeking care ($469 million)-can save hundreds of millions in costs annually in Nigeria., Conclusions: The results highlight the significant health and economic burden of poor quality antimalarials in Nigeria, and the impact of potential interventions to counter them. In order to reduce the burden of malaria and prevent antimalarials from developing resistance, policymakers and donors must understand the problem and implement interventions to reduce the impact of ineffective and harmful antimalarials., Competing Interests: The authors have declared that no competing interests exist.

Substandard and falsified medicines pose significant risks to global health, including increased deaths, prolonged treatments, and growing drug resistance. Antimalarials are one of the most common medications to be of poor quality in low- and middle-income countries. We assessed the health and economic impact of substandard and falsified antimalarials for children less than 5 years of age in the Democratic Republic of the Congo, which has one of the world's highest malaria mortality rates. We developed an agent-based model to simulate patient care-seeking behavior and medicine supply chain processes to examine the impact of antimalarial quality in Kinshasa province and Katanga region. We simulated the impact of potential interventions to improve medicinal quality, reduce stockouts, or educate caregivers. We estimated that substandard and falsified antimalarials are responsible for $20.9 million (35% of $59.6 million; 95% CI: $20.7-$21.2 million) in malaria costs in Kinshasa province and $130 million (43% of $301 million; $129-$131 million) in malaria costs in the Katanga region annually. If drug resistance to artemisinin were to develop, total annual costs of malaria could increase by $17.9 million (30%; $17.7-$18.0 million) and $73 million (24%; $72.2-$72.8 million) in Kinshasa and Katanga, respectively. Replacing substandard and falsified antimalarials with good quality medicines had a larger impact than interventions that prevented stockouts or educated caregivers. The results highlight the importance of improving access to good quality antimalarials to reduce the burden of malaria and mitigate the development of antimalarial resistance.

Background: Global efforts to address the burden of malaria have stagnated in recent years with malaria cases beginning to rise. Substandard and falsified anti-malarial treatments contribute to this stagnation. Poor quality anti-malarials directly affect health outcomes by increasing malaria morbidity and mortality, as well as threaten the effectiveness of treatment by contributing to artemisinin resistance. Research to assess the scope and impact of poor quality anti-malarials is essential to raise awareness and allocate resources to improve the quality of treatment. A probabilistic agent-based model was developed to provide country-specific estimates of the health and economic impact of poor quality anti-malarials on paediatric malaria. This paper presents the methodology and case study of the Substandard and Falsified Antimalarial Research Impact (SAFARI) model developed and applied to Uganda., Results: The total annual economic impact of malaria in Ugandan children under age five was estimated at US$614 million. Among children who sought medical care, the total economic impact was estimated at $403 million, including $57.7 million in direct costs. Substandard and falsified anti-malarials were a significant contributor to this annual burden, accounting for $31 million (8% of care-seeking children) in total economic impact involving $5.2 million in direct costs. Further, 9% of malaria deaths relating to cases seeking treatment were attributable to poor quality anti-malarials. In the event of widespread artemisinin resistance in Uganda, we simulated a 12% yearly increase in costs associated with paediatric malaria cases that sought care, inflicting $48.5 million in additional economic impact annually., Conclusions: Improving the quality of treatment is essential to combat the burden of malaria and prevent the development of drug resistance. The SAFARI model provides country-specific estimates of the health and economic impact of substandard and falsified anti-malarials to inform governments, policy makers, donors and the malaria community about the threat posed by poor quality medicines. The model findings are useful to illustrate the significance of the issue and inform policy and interventions to improve medicinal quality.

Importance: Substandard and falsified medicines burden health systems by diverting resources to ineffective or harmful therapies, causing medical complications and prolonging illnesses. However, the prevalence and economic impact of poor-quality medicines is unclear., Objective: To conduct a systematic review and meta-analysis to assess the prevalence and estimated economic burden of substandard and falsified essential medicines in low- and middle-income countries., Data Sources: Five databases (PubMed, EconLit, Global Health, Embase, and Scopus) were searched from inception until November 3, 2017., Study Selection: Publications were assessed to determine whether they examined medicine quality and the prevalence and/or economic burden of substandard and falsified medicines in low- and middle-income countries. Studies with a sample size of 50 or more were included in the meta-analysis., Data Extraction and Synthesis: The study is registered in PROSPERO and reported via the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Study quality was assessed using an adapted Medicine Quality Assessment Reporting Guidelines scoring metric. Multiple reviewers conducted the data extraction and quality assessment independently., Main Outcomes and Measures: Prevalence and/or estimated economic impact of substandard and falsified medicines., Results: Two hundred sixty-five studies that estimated the prevalence of poor-quality essential medicines in low- and middle-income countries were identified. Among 96 studies that tested 50 samples or more (67 839 total drug samples), overall prevalence of poor-quality medicines was 13.6% (95% CI, 11.0%-16.3%), with regional prevalence of 18.7% in Africa (95% CI, 12.9%-24.5%) and 13.7% in Asia (95% CI, 8.2%-19.1%). Of studies included in the meta-analysis, 19.1% (95% CI, 15.0%-23.3%) of antimalarials and 12.4% (95% CI, 7.1%-17.7%) of antibiotics were substandard or falsified. Eight approximations of the economic impact, focused primarily on market size, with poor or undisclosed methods in estimation were identified, ranging from $10 billion to $200 billion., Conclusions and Relevance: Poor-quality essential medicines are a substantial and understudied problem. Methodological standards for prevalence and rigorous economic studies estimating the burden beyond market size are needed to accurately assess the scope of the issue and inform efforts to address it. Global collaborative efforts are needed to improve supply-chain management, surveillance, and regulatory capacity in low- and middle-income countries to reduce the threat of poor-quality medicines., Trial Registration: PROSPERO Identifier: CRD42017080266.