Optimally generate policy-based evidence before scaling.

Social scientists have increasingly turned to the experimental method to understand human behaviour. One critical issue that makes solving social problems difficult is scaling up the idea from a small group to a larger group in more diverse situations. The urgency of scaling policies impacts us every day, whether it is protecting the health and safety of a community or enhancing the opportunities of future generations. Yet, a common result is that, when we scale up ideas, most experience a 'voltage drop'-that is, on scaling, the cost-benefit profile depreciates considerably. Here I argue that, to reduce voltage drops, we must optimally generate policy-based evidence. Optimality requires answering two crucial questions: what information should be generated and in what sequence. The economics underlying the science of scaling provides insights into these questions, which are in some cases at odds with conventional approaches. For example, there are important situations in which I advocate flipping the traditional social science research model to an approach that, from the beginning, produces the type of policy-based evidence that the science of scaling demands. To do so, I propose augmenting efficacy trials by including relevant tests of scale in the original discovery process, which forces the scientist to naturally start with a recognition of the big picture: what information do I need to have scaling confidence?

Cost-effective mitigation of nitrogen pollution from global croplands.

Cropland is a main source of global nitrogen pollution1,2. Mitigating nitrogen pollution from global croplands is a grand challenge because of the nature of non-point-source pollution from millions of farms and the constraints to implementing pollution-reduction measures, such as lack of financial resources and limited nitrogen-management knowledge of farmers3. Here we synthesize 1,521 field observations worldwide and identify 11 key measures that can reduce nitrogen losses from croplands to air and water by 30-70%, while increasing crop yield and nitrogen use efficiency (NUE) by 10-30% and 10-80%, respectively. Overall, adoption of this package of measures on global croplands would allow the production of 17 ± 3 Tg (1012 g) more crop nitrogen (20% increase) with 22 ± 4 Tg less nitrogen fertilizer used (21% reduction) and 26 ± 5 Tg less nitrogen pollution (32% reduction) to the environment for the considered base year of 2015. These changes could gain a global societal benefit of 476 ± 123 billion US dollars (USD) for food supply, human health, ecosystems and climate, with net mitigation costs of only 19 ± 5 billion USD, of which 15 ± 4 billion USD fertilizer saving offsets 44% of the gross mitigation cost. To mitigate nitrogen pollution from croplands in the future, innovative policies such as a nitrogen credit system (NCS) could be implemented to select, incentivize and, where necessary, subsidize the adoption of these measures.

Tackling psychosocial and capital constraints to alleviate poverty.

Many policies attempt to help extremely poor households build sustainable sources of income. Although economic interventions have predominated historically1,2, psychosocial support has attracted substantial interest3-5, particularly for its potential cost-effectiveness. Recent evidence has shown that multi-faceted 'graduation' programmes can succeed in generating sustained changes6,7. Here we show that a multi-faceted intervention can open pathways out of extreme poverty by relaxing capital and psychosocial constraints. We conducted a four-arm randomized evaluation among extremely poor female beneficiaries already enrolled in a national cash transfer government programme in Niger. The three treatment arms included group savings promotion, coaching and entrepreneurship training, and then added either a lump-sum cash grant, psychosocial interventions, or both the cash grant and psychosocial interventions. All three arms generated positive effects on economic outcomes and psychosocial well-being, but there were notable differences in the pathways and the timing of effects. Overall, the arms with psychosocial interventions were the most cost-effective, highlighting the value of including well-designed psychosocial components in government-led multi-faceted interventions for the extreme poor.

Costs in conservation: Common costly mistakes and how to avoid them.

There has been an increasingly prevalent message that data regarding costs must be included in conservation planning activities to make cost-efficient decisions. Despite the growing acceptance that socioeconomic context is critical to conservation success, the approaches to embedded economic and financial considerations into planning have not significantly evolved. Inappropriate cost data is frequently included in decisions, with the potential of compromising biodiversity and social outcomes. For each conservation planning step, this essay details common mistakes made when considering costs, proposing solutions to enable conservation managers to know when and how to include costs. Appropriate use of high-quality cost data obtained at the right scale will improve decision-making and ultimately avoid costly mistakes.

Comparative Analysis of Droplet-Based Ultra-High-Throughput Single-Cell RNA-Seq Systems.

Since its establishment in 2009, single-cell RNA sequencing (RNA-seq) has been a major driver behind progress in biomedical research. In developmental biology and stem cell studies, the ability to profile single cells confers particular benefits. Although most studies still focus on individual tissues or organs, the recent development of ultra-high-throughput single-cell RNA-seq has demonstrated potential power in characterizing more complex systems or even the entire body. However, although multiple ultra-high-throughput single-cell RNA-seq systems have attracted attention, no systematic comparison of these systems has been performed. Here, with the same cell line and bioinformatics pipeline, we developed directly comparable datasets for each of three widely used droplet-based ultra-high-throughput single-cell RNA-seq systems, inDrop, Drop-seq, and 10X Genomics Chromium. Although each system is capable of profiling single-cell transcriptomes, their detailed comparison revealed the distinguishing features and suitable applications for each system.

Meta-analysis and public policy: Reconciling the evidence on deworming.

The WHO recommends mass drug administration (MDA) for intestinal worm infections in areas with over 20% infection prevalence. Recent Cochrane meta-analyses endorse treatment of infected individuals but recommend against MDA. We conducted a theory-agnostic random-effects meta-analysis of the effect of multiple-dose MDA and a cost-effectiveness analysis. We estimate significant effects of MDA on child weight (0.15 kg, 95% CI: 0.07, 0.24; P < 0.001), mid-upper arm circumference (0.20 cm, 95% CI: 0.03, 0.37; P = 0.02), and height (0.09 cm, 95% CI: 0.01, 0.16; P = 0.02) when prevalence is over 20% but not on Hb (0.06 g/dL, 95% CI: -0.01, 0.14; P = 0.1). These results suggest that MDA is a cost-effective intervention, particularly in the settings where it is recommended by the WHO.

The economic case for scaling up health research and development: Lessons from the COVID-19 pandemic.

In response to the COVID-19 pandemic, governments directly funded vaccine research and development (R&D), quickly leading to multiple effective vaccines and resulting in enormous health and economic benefits to society. We develop a simple economic model showing this feat could potentially be repeated for other health challenges. Based on inputs from the economic and medical literatures, the model yields estimates of optimal R&D spending on treatments and vaccines for known diseases. Taking a global and societal perspective, we estimate the social benefits of such spending and a corresponding rate of return. Applications to Streptococcus A vaccines and Alzheimer's disease treatments demonstrate the potential of enhanced research and development funding to unlock massive global health and health-related benefits. We estimate that these benefits range from 2 to 60 trillion (2020 US$) and that the corresponding rates of return on R&D spending range from 12% to 23% per year for 30 y. We discuss the current shortfall in R&D spending and public policies that can move current funding closer to the optimal level.

Cost-effectiveness of prophylaxis with recombinant vs plasma-derived VWF in severe von Willebrand disease in the United States.

ABSTRACT: We evaluated the cost-effectiveness of prophylaxis with recombinant von Willebrand factor (rVWF) vs with plasma-derived von Willebrand factor (pdVWF) for patients with severe Von Willebrand disease. We found that rVWF is a cost-saving factor replacement compared with pdVWF across all willingness-to-pay thresholds in the United States.

Global priority areas for ecosystem restoration.

Extensive ecosystem restoration is increasingly seen as being central to conserving biodiversity1 and stabilizing the climate of the Earth2. Although ambitious national and global targets have been set, global priority areas that account for spatial variation in benefits and costs have yet to be identified. Here we develop and apply a multicriteria optimization approach that identifies priority areas for restoration across all terrestrial biomes, and estimates their benefits and costs. We find that restoring 15% of converted lands in priority areas could avoid 60% of expected extinctions while sequestering 299 gigatonnes of CO2-30% of the total CO2 increase in the atmosphere since the Industrial Revolution. The inclusion of several biomes is key to achieving multiple benefits. Cost effectiveness can increase up to 13-fold when spatial allocation is optimized using our multicriteria approach, which highlights the importance of spatial planning. Our results confirm the vast potential contributions of restoration to addressing global challenges, while underscoring the necessity of pursuing these goals synergistically.

Effectiveness of kangaroo mother care before clinical stabilisation versus standard care among neonates at five hospitals in Uganda (OMWaNA): a parallel-group, individually randomised controlled trial and economic evaluation.

BACKGROUND: Preterm birth is the leading cause of death in children younger than 5 years worldwide. WHO recommends kangaroo mother care (KMC); however, its effects on mortality in sub-Saharan Africa and its relative costs remain unclear. We aimed to compare the effectiveness, safety, costs, and cost-effectiveness of KMC initiated before clinical stabilisation versus standard care in neonates weighing up to 2000 g. METHODS: We conducted a parallel-group, individually randomised controlled trial in five hospitals across Uganda. Singleton or twin neonates aged younger than 48 h weighing 700-2000 g without life-threatening clinical instability were eligible for inclusion. We randomly assigned (1:1) neonates to either KMC initiated before stabilisation (intervention group) or standard care (control group) via a computer-generated random allocation sequence with permuted blocks of varying sizes, stratified by birthweight and recruitment site. Parents, caregivers, and health-care workers were unmasked to treatment allocation; however, the independent statistician who conducted the analyses was masked. After randomisation, neonates in the intervention group were placed prone and skin-to-skin on the caregiver's chest, secured with a KMC wrap. Neonates in the control group were cared for in an incubator or radiant heater, as per hospital practice; KMC was not initiated until stability criteria were met. The primary outcome was all-cause neonatal mortality at 7 days, analysed by intention to treat. The economic evaluation assessed incremental costs and cost-effectiveness from a disaggregated societal perspective. This trial is registered with ClinicalTrials.gov, NCT02811432. FINDINGS: Between Oct 9, 2019, and July 31, 2022, 2221 neonates were randomly assigned: 1110 (50·0%) neonates to the intervention group and 1111 (50·0%) neonates to the control group. From randomisation to age 7 days, 81 (7·5%) of 1083 neonates in the intervention group and 83 (7·5%) of 1102 neonates in the control group died (adjusted relative risk [RR] 0·97 [95% CI 0·74-1·28]; p=0·85). From randomisation to 28 days, 119 (11·3%) of 1051 neonates in the intervention group and 134 (12·8%) of 1049 neonates in the control group died (RR 0·88 [0·71-1·09]; p=0·23). Even if policy makers place no value on averting neonatal deaths, the intervention would have 97% probability from the provider perspective and 84% probability from the societal perspective of being more cost-effective than standard care. INTERPRETATION: KMC initiated before stabilisation did not reduce early neonatal mortality; however, it was cost-effective from the societal and provider perspectives compared with standard care. Additional investment in neonatal care is needed for increased impact, particularly in sub-Saharan Africa. FUNDING: Joint Global Health Trials scheme of the Department of Health and Social Care, Foreign, Commonwealth and Development Office, UKRI Medical Research Council, and Wellcome Trust; Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Clinical effectiveness of the psychological therapy Mental Health Intervention for Children with Epilepsy in addition to usual care compared with assessment-enhanced usual care alone: a multicentre, randomised controlled clinical trial in the UK.

BACKGROUND: Mental health difficulties are common in children and young people with chronic health conditions, but many of those in need do not access evidence-based psychological treatments. The study aim was to evaluate the clinical effectiveness of integrated mental health treatment for children and young people with epilepsy, a common chronic health condition known to be associated with a particularly high rate of co-occurring mental health difficulties. METHODS: We conducted a parallel group, multicentre, open-label, randomised controlled trial of participants aged 3-18 years, attending epilepsy clinics across England and Northern Ireland who met diagnostic criteria for a common mental health disorder. Participants were randomised (1:1; using an independent web-based system) to receive the Mental Health Intervention for Children with Epilepsy (MICE) in addition to usual care, or assessment-enhanced usual care alone (control). Children and young people in both groups received a full diagnostic mental health assessment. MICE was a modular psychological intervention designed to treat common mental health conditions in children and young people using evidence-based approaches such as cognitive behaviour therapy and behavioural parenting strategies. Usual care for mental health disorders varied by site but typically included referral to appropriate services. Participants, along with their caregivers, and clinicians were not masked to treatment allocation but statisticians were masked until the point of analysis. The primary outcome, analysed by modified intention-to-treat, was the parent-report Strengths and Difficulties Questionnaire (SDQ) at 6 months post-randomisation. The study is complete and registered with ISRCTN (57823197). FINDINGS: 1401 young people were potentially deemed eligible for study inclusion. Following the exclusion of 531 young people, 870 participants were assessed for eligibility and completed the SDQ, and 480 caregivers provided consent for study inclusion between May 20, 2019, and Jan 31, 2022. Between Aug 28, 2019, and Feb 21, 2022, 334 participants (mean ages 10·5 years [SD 3·6] in the MICE group vs 10·3 [4·0] in control group at baseline) were randomly assigned to an intervention using minimisation balanced by age, primary mental health disorder, diagnosis of intellectual disability, and autistic spectrum disorder at baseline. 168 (50%) of the participants were female and 166 (50%) were male. 166 participants were randomly assigned to the MICE group and 168 were randomly assigned to the control group. At 6 months, the mean SDQ difficulties for the 148 participants in the MICE group was 17·6 (SD 6·3) and 19·6 (6·1) for the 148 participants in the control group. The adjusted effect of MICE was -1·7 (95% CI -2·8 to -0·5; p=0·0040; Cohen's d, 0·3). 14 (8%) patients in the MICE group experienced at least one serious adverse event compared with 24 (14%) in the control group. 68% percent of serious adverse events (50 events) were admission due to seizures. INTERPRETATION: MICE was superior to assessment-enhanced usual care in improving symptoms of emotional and behavioural difficulties in young people with epilepsy and common mental health disorders. The trial therefore shows that mental health comorbidities can be effectively and safely treated by a variety of clinicians, utilising an integrated intervention across ages and in the context of intellectual disability and autism. The evidence from this trial suggests that such a model should be fully embedded in epilepsy services and serves as a model for other chronic health conditions in young people. FUNDING: UK National Institute for Health Research Programme Grants for Applied Research programme and Epilepsy Research UK Endeavour Project Grant.

Colonoscopy vs the Fecal Immunochemical Test: Which is Best?

Although there is no debate around the effectiveness of colorectal cancer screening in reducing disease burden, there remains a question regarding the most effective and cost-effective screening modality. Current United States guidelines present a panel of options that include the 2 most commonly used modalities, colonoscopy and stool testing with the fecal immunochemical test (FIT). Large-scale comparative effectiveness trials comparing colonoscopy and FIT for colorectal cancer outcomes are underway, but results are not yet available. This review will separately state the "best case" for FIT and colonoscopy as the screening tool of first choice. In addition, the review will examine these modalities from a health economics perspective to provide the reader further context about the relative advantages of these commonly used tests.

The Economic Iceberg of Celiac Disease: More Than the Cost of Gluten-Free Food.

Celiac disease (CeD) is a chronic autoimmune disorder of global relevance, with the potential for acute and long-term complications. However, the economic burden of CeD is rarely considered and largely thought of as limited to the cost of gluten-free food. Fortunately, recent research has shed light on the various societal costs of CeD across the health care continuum. This article summarizes the current evidence on the economic impacts of CeD, which suggest that the societal economic burden of CeD stretches beyond the cost of gluten-free food. This review provides ample evidence of larger but hidden costs related to excess health care use for complications and comorbidities, as well as reduced productivity. Although significant advances are expected in the management of CeD, their effect on the economic burden of CeD remain uncertain. The aim of this review was to inform stakeholders across society and contribute to improved policies to support patients with CeD.

Effectiveness and Cost-Effectiveness of Colorectal Cancer Screening With a Blood Test That Meets the Centers for Medicare & Medicaid Services Coverage Decision.

BACKGROUND & AIMS: A blood-based colorectal cancer (CRC) screening test may increase screening participation. However, blood tests may be less effective than current guideline-endorsed options. The Centers for Medicare & Medicaid Services (CMS) covers blood tests with sensitivity of at least 74% for detection of CRC and specificity of at least 90%. In this study, we investigate whether a blood test that meets these criteria is cost-effective. METHODS: Three microsimulation models for CRC (MISCAN-Colon, CRC-SPIN, and SimCRC) were used to estimate the effectiveness and cost-effectiveness of triennial blood-based screening (from ages 45 to 75 years) compared to no screening, annual fecal immunochemical testing (FIT), triennial stool DNA testing combined with an FIT assay, and colonoscopy screening every 10 years. The CMS coverage criteria were used as performance characteristics of the hypothetical blood test. We varied screening ages, test performance characteristics, and screening uptake in a sensitivity analysis. RESULTS: Without screening, the models predicted 77-88 CRC cases and 32-36 CRC deaths per 1000 individuals, costing $5.3-$5.8 million. Compared to no screening, blood-based screening was cost-effective, with an additional cost of $25,600-$43,700 per quality-adjusted life-year gained (QALYG). However, compared to FIT, triennial stool DNA testing combined with FIT, and colonoscopy, blood-based screening was not cost-effective, with both a decrease in QALYG and an increase in costs. FIT remained more effective (+5-24 QALYG) and less costly (-$3.2 to -$3.5 million) than blood-based screening even when uptake of blood-based screening was 20 percentage points higher than uptake of FIT. CONCLUSION: Even with higher screening uptake, triennial blood-based screening, with the CMS-specified minimum performance sensitivity of 74% and specificity of 90%, was not projected to be cost-effective compared with established strategies for colorectal cancer screening.

Comparative Effectiveness and Cost-Effectiveness of Colorectal Cancer Screening With Blood-Based Biomarkers (Liquid Biopsy) vs Fecal Tests or Colonoscopy.

BACKGROUND & AIMS: Colorectal cancer (CRC) screening is highly effective but underused. Blood-based biomarkers (liquid biopsy) could improve screening participation. METHODS: Using our established Markov model, screening every 3 years with a blood-based test that meets minimum Centers for Medicare & Medicaid Services' thresholds (CMSmin) (CRC sensitivity 74%, specificity 90%) was compared with established alternatives. Test attributes were varied in sensitivity analyses. RESULTS: CMSmin reduced CRC incidence by 40% and CRC mortality by 52% vs no screening. These reductions were less profound than the 68%-79% and 73%-81%, respectively, achieved with multi-target stool DNA (Cologuard; Exact Sciences) every 3 years, annual fecal immunochemical testing (FIT), or colonoscopy every 10 years. Assuming the same cost as multi-target stool DNA, CMSmin cost $28,500/quality-adjusted life-year gained vs no screening, but FIT, colonoscopy, and multi-target stool DNA were less costly and more effective. CMSmin would match FIT's clinical outcomes if it achieved 1.4- to 1.8-fold FIT's participation rate. Advanced precancerous lesion (APL) sensitivity was a key determinant of a test's effectiveness. A paradigm-changing blood-based test (sensitivity >90% for CRC and 80% for APL; 90% specificity; cost ≤$120-$140) would be cost-effective vs FIT at comparable participation. CONCLUSIONS: CMSmin could contribute to CRC control by achieving screening in those who will not use established methods. Substituting blood-based testing for established effective CRC screening methods will require higher CRC and APL sensitivities that deliver programmatic benefits matching those of FIT. High APL sensitivity, which can result in CRC prevention, should be a top priority for screening test developers. APL detection should not be penalized by a definition of test specificity that focuses on CRC only.

A computational framework of routine test data for the cost-effective chronic disease prediction.

Chronic diseases, because of insidious onset and long latent period, have become the major global disease burden. However, the current chronic disease diagnosis methods based on genetic markers or imaging analysis are challenging to promote completely due to high costs and cannot reach universality and popularization. This study analyzed massive data from routine blood and biochemical test of 32 448 patients and developed a novel framework for cost-effective chronic disease prediction with high accuracy (AUC 87.32%). Based on the best-performing XGBoost algorithm, 20 classification models were further constructed for 17 types of chronic diseases, including 9 types of cancers, 5 types of cardiovascular diseases and 3 types of mental illness. The highest accuracy of the model was 90.13% for cardia cancer, and the lowest was 76.38% for rectal cancer. The model interpretation with the SHAP algorithm showed that CREA, R-CV, GLU and NEUT% might be important indices to identify the most chronic diseases. PDW and R-CV are also discovered to be crucial indices in classifying the three types of chronic diseases (cardiovascular disease, cancer and mental illness). In addition, R-CV has a higher specificity for cancer, ALP for cardiovascular disease and GLU for mental illness. The association between chronic diseases was further revealed. At last, we build a user-friendly explainable machine-learning-based clinical decision support system (DisPioneer: http://bioinfor.imu.edu.cn/dispioneer) to assist in predicting, classifying and treating chronic diseases. This cost-effective work with simple blood tests will benefit more people and motivate clinical implementation and further investigation of chronic diseases prevention and surveillance program.

Real-World Healthcare Cost Savings and Reduced Relapse Rate with Off-Label Rituximab versus Disease-Modifying Treatments Approved for Relapsing-Remitting Multiple Sclerosis: A Nationwide Cost-Effectiveness Study.

OBJECTIVE: Although off-label use of rituximab is a common alternative to disease-modifying therapies (DMTs) approved for multiple sclerosis (MS) in several countries, the impact of this on treatment cost-effectiveness is not well known. METHODS: We evaluated the relative cost-effectiveness of rituximab and MS-approved DMTs in a register-based cohort study of Swedish residents with relapsing-remitting MS, aged 18-65 years, starting treatment with rituximab, natalizumab, fingolimod, or dimethyl fumarate between January 2010 and July 2016, and followed through July 2021 (n = 5,924). By linking the population-based Swedish MS register to several Swedish health care and demographic registers, we estimated health care costs in relation to number of relapses, over 5 years from treatment start. Differences between treatments were estimated in inverse probability of treatment-weighted regression models, adjusting for a broad range of potential confounders covering demographics, medical history, and MS-related clinical characteristics. RESULTS: Off-label rituximab was associated with both lower total health care costs (mean cost savings ranged $35,000-$66,000 vs. each approved DMT), and fewer relapses (mean number of prevented relapses ranged 0.12-0.22), per started therapy over 5 years. Results were robust to variations in discounting and pricing of health care visits, with the main driver of cost-savings being the price of the index drug itself. INTERPRETATION: The cost-effectiveness of rituximab dominated the MS-approved alternatives. Off-label, low-dose rituximab should be considered for persons with MS and could reduce barriers to treatment, especially in resource-limited settings. ANN NEUROL 2024;95:1099-1111.

Application of improved GalNAc conjugation in development of cost-effective siRNA therapies targeting cardiovascular diseases.

N-Acetylgalactosamine (GalNAc)-conjugated small interfering RNA (siRNA) therapies have received approval for treating both orphan and prevalent diseases. To improve in vivo efficacy and streamline the chemical synthesis process for efficient and cost-effective manufacturing, we conducted this study to identify better designs of GalNAc-siRNA conjugates for therapeutic development. Here, we present data on redesigned GalNAc-based ligands conjugated with siRNAs against angiopoietin-like 3 (ANGPTL3) and lipoprotein (a) (Lp(a)), two target molecules with the potential to address large unmet medical needs in atherosclerotic cardiovascular diseases. By attaching a novel pyran-derived scaffold to serial monovalent GalNAc units before solid-phase oligonucleotide synthesis, we achieved increased GalNAc-siRNA production efficiency with fewer synthesis steps compared to the standard triantennary GalNAc construct L96. The improved GalNAc-siRNA conjugates demonstrated equivalent or superior in vivo efficacy compared to triantennary GalNAc-conjugated siRNAs.

Comparative Analysis of Single-Cell RNA Sequencing Methods.

Single-cell RNA sequencing (scRNA-seq) offers new possibilities to address biological and medical questions. However, systematic comparisons of the performance of diverse scRNA-seq protocols are lacking. We generated data from 583 mouse embryonic stem cells to evaluate six prominent scRNA-seq methods: CEL-seq2, Drop-seq, MARS-seq, SCRB-seq, Smart-seq, and Smart-seq2. While Smart-seq2 detected the most genes per cell and across cells, CEL-seq2, Drop-seq, MARS-seq, and SCRB-seq quantified mRNA levels with less amplification noise due to the use of unique molecular identifiers (UMIs). Power simulations at different sequencing depths showed that Drop-seq is more cost-efficient for transcriptome quantification of large numbers of cells, while MARS-seq, SCRB-seq, and Smart-seq2 are more efficient when analyzing fewer cells. Our quantitative comparison offers the basis for an informed choice among six prominent scRNA-seq methods, and it provides a framework for benchmarking further improvements of scRNA-seq protocols.

High-Efficiency Particulate Air Filters for Preventing Wildfire-related Asthma Complications: A Cost-Effectiveness Study.

Rationale: Air pollution caused by wildfire smoke is linked to adverse health outcomes, especially for people living with asthma. Objectives: To evaluate whether government rebates for high-efficiency particulate air (HEPA) filters, which reduce concentrations of smoke particles indoors, are cost effective in managing asthma and preventing exacerbations in British Columbia (BC), Canada. Methods: We used a Markov model to analyze health states for asthma control, exacerbation severity, and death over a retrospective time horizon of 5 years (2018-2022). Concentrations of wildfire smoke-derived particulate matter with an aerodynamic diameter ⩽2.5 µm (PM2.5) from the Canadian Optimized Statistical Smoke Exposure Model and relevant literature informed the model. The base-case analysis assumed continuous use of a HEPA filter. Costs and quality-adjusted life-years (QALYs) resulting from varying rebates were computed for each Health Service Delivery Area (HSDA). Measurements and Main Results: In the base-case analysis, HEPA filter use resulted in increased costs of $83.34 (SE, $1.03) and increased QALYs of 0.0011 (SE, 0.0001) per person. The average incremental cost-effectiveness ratio among BC HSDAs was $74,652/QALY (SE, $3,517), with incremental cost-effectiveness ratios ranging from $40,509 to $89,206 per QALY in HSDAs. Across the province, the intervention was projected to prevent 4,418 exacerbations requiring systemic corticosteroids, 643 emergency department visits, and 425 hospitalizations during the 5-year time horizon. A full rebate was cost effective in 1 of the 16 HSDAs across BC. The probability of cost-effectiveness ranged from 0.1% to 74.8% across HSDAs. A $100 rebate was cost effective in most HSDAs. Conclusions: The cost-effectiveness of HEPA filters in managing wildfire smoke-related asthma issues in BC varies by region. Government rebates up to two-thirds of the filter cost are generally cost effective, with a full rebate being cost effective only in Kootenay Boundary.