Model-based cost-effectiveness analysis of a multiplex lateral flow rapid diagnostic test for acute non-malarial febrile illness in rural South and Southeast Asian primary care

Abstract

ABSTRACTBackgroundMultiplex lateral flow rapid diagnostic tests (LF-RDTs) may aid management of patients with acute non-malarial fever (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.MethodsA 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 2022 US dollars, 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 GDP.FindingsCompared to standard of care, LF-RDT-augmented clinical assessment was dominant in Cambodia, being more effective and cost-saving. The cost per DALY averted in Bangladesh was $482, slightly above the conservative opportunity cost-based willingness-to-pay threshold of $388 and considerably lower than the GDP-based threshold of $2,687. The intervention remained dominant in Cambodia and well below the GDP-based threshold in Bangladesh when antimicrobial resistance costs were disregarded.InterpretationThese 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 cost-effectiveness is highly likely in some target settings and possible in others.FundingWellcome Trust, UK Government, Royal Australasian College of Physicians, Rotary Foundation.RESEARCH IN CONTEXTEvidence before this studyThe diagnosis and management of acute non-malarial febrile illness in rural South and Southeast Asian low- and middle-income countries remains challenging; multiplex lateral flow rapid diagnostic tests have been proposed as a possible solution. In view of the scant evidence on the epidemiology of acute non-malarial febrile illness in this region, we recently conducted an international Delphi survey to identify priority analytes for inclusion in such a putative test with capillary blood as the substrate. The main finding was that this test should be able to diagnose enteric fever and dengue, at a minimum; there was also support for including C-reactive protein as a means of differentiating viral from non-viral causes of NMFI to guide empirical antibiotic prescribing. However, we could not identify any economic evaluations of the cost-effectiveness of any such multiplex tests following a search of standard databases using the keywords ‘fever’, ‘febrile’, ‘multiplex’, ‘South Asia’ and ‘Southeast Asia’ on 2 March 2023.Added value of this studyBangladesh and Cambodia are lower-middle income countries in South and Southeast Asia, respectively, which are representative of the settings in which the test will be most useful. This country-specific assessment of the cost-effectiveness of such an urgently needed diagnostic tool provides vital information to guide decision-making by researcher, industry, and policymaker stakeholders on the development and deployment of such a test in terms of performance characteristics and pricing.Implications of all the available evidenceThe cost-effectiveness of this putative multiplex lateral flow rapid diagnostic test is dependent not only on its inherent performance and pricing, but on context-specific factors. Optimizing the specificity of component assays, as well as mechanisms to lower prices in markets where the test is not cost-effective, have the potential to ensure cost-effectiveness in as many target countries as possible.