Malaria and Economic Evaluation Methods: Challenges and Opportunities.

There is a growing evidence base on the cost effectiveness of malaria interventions. However, certain characteristics of malaria decision problems present a challenge to the application of healthcare economic evaluation methods. This paper identifies five such challenges. The complexities of (i) declining incidence and cost effectiveness in the context of an elimination campaign; (ii) international aid and its effect on resource constraints; and (iii) supranational priority setting, all affect how health economists might use a cost-effectiveness threshold. Consensus and guidance on how to determine and interpret cost-effectiveness thresholds in the context of internationally financed elimination campaigns is greatly needed. (iv) Malaria interventions are often complimentary and evaluations may need to construct intervention bundles to represent relevant policy positions as sets of mutually exclusive alternatives. (v) Geographic targeting is a key aspect of malaria policy making that is only beginning to be addressed in economic evaluations. An approach to budget-based geographic resource allocation is described in an accompanying paper in this issue and addresses some of these methodological challenges

Cost, health impacts and cost effectiveness of iceless refrigeration in India's last-mile vaccine cold chain delivery

Background: Compared with ice-based vaccine carriers (IBVCs), iceless vaccine carrier (ILVC) last-mile delivery could optimize vaccine effectiveness by reducing spoilage. We estimated ILVC-associated spoilage costs averted and cost effectiveness. Methods: IBVC vaccine spoilage costs were estimated for six vaccines. ILVC incremental costs were based on yearly ILVC cost over total doses. Cost effectiveness was estimated via Markov modeling of rotavirus vaccine. Results: The spoilage cost using IBVCs was USD9 603 294. Using ILVCs, the incremental cost per vaccine dose was USD0.026, the cost-benefit ratio was 0.28, the number of averted disability-adjusted life years was 0.03 per child and there was a saving of USD0.80 per child vaccinated. Conclusions: ILVCs may bring cost savings and health gains compared with IBVCs

A cost-utility and budget impact analysis of allogeneic hematopoietic stem cell transplantation for severe thalassemic patients in Thailand

<p>Abstract</p> <p>Background</p> <p>Hematopoietic stem cell transplantation (HSCT) is the only curative treatment available to severe thalassemic patients. The treatment, however, is very costly, particularly in the context of low and middle income countries, and no studies have been carried out to explore its economic justifiability. This study aimed to estimate the cost-utility of HSCT compared with blood transfusions combined with iron chelating therapy (BT-ICT) for severe thalassemia in Thailand, and to investigate the affordability of HSCT using a budget impact analysis.</p> <p>Methods</p> <p>A Markov model was used to estimate the relevant costs and health outcomes over the patients' lifetimes taking a societal perspective as recommended by Thailand's health technology assessment guidelines. All future costs and outcomes were discounted at a rate of 3% per annum. Primary outcomes of interest were lifetime costs, quality adjusted life years (QALYs) gained, and the incremental cost-effectiveness ratio (ICER) in Thai baht (THB) per QALY gained.</p> <p>Results</p> <p>Compared to BT-ICT, the incremental cost-effectiveness ratio increased with patient age from 80,700 to 183,000 THB per QALY gained for related HSCT and 209,000 to 953,000 THB per QALY gained for unrelated HSCT among patients aged 1 to 15 years (US$1= 34 THB). The governmental budget impact analysis showed that providing 200 related HSCT to patients aged 1 to 10 years, in accordance with the current infrastructure limitations, would initially require approximately 90 million additional THB per year.</p> <p>Conclusions</p> <p>At a societal willingness to pay of 100,000 THB per QALY gained, related HSCT was likely to be a cost-effective and affordable treatment for young children with severe thalassemia in Thailand.</p

Perceptions and priorities for the development of multiplex rapid diagnostic tests for acute non-malarial fever in rural South and Southeast Asia: an international modified e-Delphi survey

Background Fever is a common presenting symptom in low- and middle-income countries (LMICs). It was previously assumed that malaria was the cause in such patients, but its incidence has declined rapidly. The urgent need to develop point-of-care tests for the most important causes of non-malarial acute febrile illness is hampered by the lack of robust epidemiological data. We sought to obtain expert consensus on analytes which should be prioritized for inclusion in fingerprick blood-based multiplex lateral flow rapid diagnostic tests (LF-RDTs) targeted towards four categories of patients with acute non-malarial fever in South and Southeast Asian LMICs, stratified by age (paediatric vs. adult) and care setting (primary vs. secondary care). Methodology/Principal findings We conducted a two-round modified e-Delphi survey. A total of 84 panellists were invited, consisting of seven each from 12 countries, divided into three regional panels (Mainland Southeast Asia, Maritime Southeast Asia, and South Asia). Panellists were asked to rank their top seven analytes for inclusion in LF-RDTs to be used in each patient category, justify their choices, and indicate whether such LF-RDTs should be incorporated into algorithm-based clinical decision support tools. Thirty-six panellists (43%) participated in the first round and 44 (52%) in the second. There was consensus that such LF-RDTs should be incorporated into clinical decision support tools. At a minimum, these LF-RDTs should be able to diagnose dengue and enteric fever in all patient categories. There was a clear preference to develop LF-RDTs for pathogens not readily detected by existing technologies, and for direct diagnosis through antigen detection. Pathogen biomarkers were prioritized over host inflammatory biomarkers, with CRP being the only one ranked consistently highly. Conclusions/Significance Our results provide guidance on prioritizing analytes for inclusion in context-specific multiplex LF-RDTs and similar platforms for non-malarial acute febrile illness, for which there is an urgent unmet need

Modelling the cost-effectiveness of pulse oximetry in primary care management of acute respiratory infection in rural northern Thailand

Objectives We aimed to determine the cost-effectiveness of supplementing standard care with pulse oximetry among children <5 years with acute respiratory infection (ARI) presenting to 32 primary care units in a rural district (total population 241,436) of Chiang Rai province, Thailand, and to assess the economic effects of extending pulse oximetry to older patients with ARI in this setting. Methods We performed a model-based cost-effectiveness analysis from a health systems perspective. Decision trees were constructed for three patient categories (children <5 years, children 5–14 years, and adults), with a 1-year time horizon. Model parameters were based on data from 49,958 patients included in a review of acute infection management in the 32 primary care units, published studies, and procurement price lists. Parameters were varied in deterministic sensitivity analyses. Costs were expressed in 2021 US dollars with a willingness-to-pay threshold per DALY averted of 8624 US dollars. Results The annual direct cost of pulse oximetry, associated staff, training, and monitoring was 24,243 US dollars. It reduced deaths from severe lower respiratory tract infections in children <5 years by 0.19 per 100,000 patients annually. In our population of 14,075 children <5 years, this was equivalent to 2.0 DALYs averted per year. When downstream costs such as those related to hospitalisation and inappropriate antibiotic prescription were considered, pulse oximetry dominated standard care, saving 12,757 US dollars annually. This intervention yielded smaller mortality gains in older patients but resulted in further cost savings, primarily by reducing inappropriate antibiotic prescriptions in these age groups. The dominance of the intervention was also demonstrated in all sensitivity analyses. Conclusions Pulse oximetry is a life-saving, cost-effective adjunct in ARI primary care management in rural northern Thailand. This finding is likely to be generalisable to neighbouring countries with similar disease epidemiology and health systems

Cost-effectiveness analysis of a multiplex lateral flow rapid diagnostic test for acute non-malarial febrile illness in rural Cambodia and Bangladesh

Background Multiplex lateral flow rapid diagnostic tests (LF-RDTs) may aid management of patients with acute non-malarial febrile illness (NMFI) in rural south and southeast Asia. We aimed to evaluate the cost-effectiveness in Cambodia and Bangladesh of a putative, as-yet-undeveloped LF-RDT capable of diagnosing enteric fever and dengue, as well as measuring C-reactive protein (CRP) to guide antibiotic prescription, in primary care patients with acute NMFI. Methods A country-specific decision tree model-based cost-effectiveness analysis was conducted from a health system plus limited societal perspective considering the cost of antimicrobial resistance. Parameters were based on data from a large observational study on the regional epidemiology of acute febrile illness, published studies, and procurement price lists. Costs were expressed in US dollars (value in 2022), and cost-effectiveness evaluated by comparing incremental cost-effectiveness ratios with conservative opportunity cost-based willingness-to-pay thresholds and the more widely used threshold of per capita gross domestic product (GDP). Findings Compared to standard of care, LF-RDT-augmented clinical assessment was dominant in Cambodia, being more effective and cost-saving. The cost per disability-adjusted life year (DALY) averted in Bangladesh was 482 US dollars , slightly above the conservative opportunity cost-based willingness-to-pay threshold of 388 US dollars and considerably lower than the GDP-based threshold of 2687 US dollars . The intervention remained dominant in Cambodia and well below the GDP-based threshold in Bangladesh when antimicrobial resistance costs were disregarded. Interpretation These findings provide guidance for academic, industry, and policymaker stakeholders involved in acute NMFI diagnostics. While definitive conclusions cannot be made in the absence of established thresholds, our results suggest that similar results are highly likely in some target settings and possible in others. Funding Wellcome Trust, UK Government, Royal Australasian College of Physicians, and Rotary Foundation

The social role of C-reactive protein point-of-care testing to guide antibiotic prescription in Northern Thailand

New and affordable point-of-care testing (POCT) solutions are hoped to guide antibiotic prescription and to help limit antimicrobial resistance (AMR)—especially in low- and middle-income countries where resource constraints often prevent extensive diagnostic testing. Anthropological and sociological research has illuminated the role and impact of rapid point-of-care malaria testing. This paper expands our knowledge about the social implications of non-malarial POCT, using the case study of a C-reactive-protein point-of-care testing (CRP POCT) clinical trial with febrile patients at primary-care-level health centres in Chiang Rai province, northern Thailand. We investigate the social role of CRP POCT through its interactions with (a) the healthcare workers who use it, (b) the patients whose routine care is affected by the test, and (c) the existing patient-health system linkages that might resonate or interfere with CRP POCT. We conduct a thematic analysis of data from 58 purposively sampled pre- and post-intervention patients and healthcare workers in August 2016 and May 2017. We find widespread positive attitudes towards the test among patients and healthcare workers. Patients’ views are influenced by an understanding of CRP POCT as a comprehensive blood test that provides specific diagnosis and that corresponds to notions of good care. Healthcare workers use the test to support their negotiations with patients but also to legitimise ethical decisions in an increasingly restrictive antibiotic policy environment. We hypothesise that CRP POCT could entail greater patient adherence to recommended antibiotic treatment, but it could also encourage riskier health behaviour and entail potentially adverse equity implications for patients across generations and socioeconomic strata. Our empirical findings inform the clinical literature on increasingly propagated point-of-care biomarker tests to guide antibiotic prescriptions, and we contribute to the anthropological and sociological literature through a novel conceptualisation of the patient-health system interface as an activity space into which biomarker testing is introduced

Inter-prescriber variability in the decision to prescribe antibiotics to febrile patients attending primary care in Myanmar

Background: Most antibiotic prescribing occurs in primary care. Even within the same health facility, there may be differences between prescribers in their tendency to prescribe antibiotics, which may be masked by summary data. We aimed to quantify prescriber variability in antibiotic prescription to patients with acute fever in primary care clinics in Myanmar. Methods: We conducted a secondary analysis of prescribing data from 1090 patient consultations with 40 prescribing doctors from a trial investigating the effect of point-of-care C-reactive protein (CRP) tests on antibiotic prescription for acute fever. We used multilevel logistic regression models to assess inter-prescriber variability in the decision to prescribe antibiotics. Results: The median odds ratio (MOR) in the unadjusted model was 1.82 (95% CI: 1.47–2.56) indicating that when two prescribers from this population are randomly selected then in half of these pairs the odds of prescription will be greater than 1.82-fold higher in one prescriber than the other. The estimated variability from this sample of prescribers corresponds to a population of prescribers where the top 25% of prescribers will prescribe antibiotics to over 41% of patients while the bottom 25% will prescribe antibiotics to less than 23% of patients. Inter-prescriber variation in antibiotic prescribing remained after adjustment for patient characteristics and CRP information (P < 0.001). Conclusions: Despite sharing the same management guidelines, there was substantial inter-prescriber variation in antibiotic prescription to patients with acute fever. This variation should be considered when designing trials and stewardship programmes aiming to reduce inappropriate antibiotic prescribing

A Comparison of Patients' Local Conceptions of Illness and Medicines in the Context of C-Reactive Protein Biomarker Testing in Chiang Rai and Yangon.

Antibiotic resistance is not solely a medical but also a social problem, influenced partly by patients' treatment-seeking behavior and their conceptions of illness and medicines. Situated within the context of a clinical trial of C-reactive protein (CRP) biomarker testing to reduce antibiotic over-prescription at the primary care level, our study explores and compares the narratives of 58 fever patients in Chiang Rai (Thailand) and Yangon (Myanmar). Our objectives are to 1) compare local conceptions of illness and medicines in relation to health-care seeking and antibiotic demand; and to 2) understand how these conceptions could influence CRP point-of-care testing (POCT) at the primary care level in low- and middle-income country settings. We thereby go beyond the current knowledge about antimicrobial resistance and CRP POCT, which consists primarily of clinical research and quantitative data. We find that CRP POCT in Chiang Rai and Yangon interacted with fever patients' preexisting conceptions of illness and medicines, their treatment-seeking behavior, and their health-care experiences, which has led to new interpretations of the test, potentially unforeseen exclusion patterns, implications for patients' self-assessed illness severity, and an increase in the status of the formal health-care facilities that provide the test. Although we expected that local conceptions of illness diverge from inbuilt assumptions of clinical interventions, we conclude that this mismatch can undermine the intervention and potentially reproduce problematic equity patterns among CRP POCT users and nonusers. As a partial solution, implementers may consider applying the test after clinical examination to validate rather than direct prescription processes

Cost of treating inpatient falciparum malaria on the Thai-Myanmar border.

BACKGROUND: Despite demonstrated benefits and World Health Organization (WHO) endorsement, parenteral artesunate is the recommended treatment for patients with severe Plasmodium falciparum malaria in only one fifth of endemic countries. One possible reason for this slow uptake is that a treatment course of parenteral artesunate is costlier than quinine and might, therefore, pose a substantial economic burden to health care systems. This analysis presents a detailed account of the resources used in treating falciparum malaria by either parenteral artesunate or quinine in a hospital on the Thai-Myanmar border. METHODS: The analysis used data from four studies, with random allocation of inpatients with falciparum malaria to treatment with parenteral artesunate or quinine, conducted in Mae Sot Hospital, Thailand from 1995 to 2001. Detailed resource use data were collected during admission and unit costs from the 2008 hospital price list were applied to these. Total admission costs were broken down into five categories: 1) medication; 2) intravenous fluids; 3) disposables; 4) laboratory tests; and 5) services. RESULTS: While the medication costs were higher for patients treated with artesunate, total admission costs were similar in those treated with quinine, US$243 (95$ 190 (95% CI: 131.0-263.2) (P=0.375). For cases classified as severe malaria (59%), the total cost of admission was US$298 (95$ 284 (95% CI: 181.3-407) in the artesunate group (P=0.869). CONCLUSION: This analysis finds no evidence for a difference in total admission costs for malaria inpatients treated with artesunate as compared with quinine. Assuming this is generalizable to other settings, the higher cost of a course of artesunate should not be considered a barrier for its implementation in the treatment of malaria