Cost-effectiveness of axicabtagene ciloleucel for adult patients with relapsed or refractory follicular lymphoma in the United States.

OBJECTIVES: The results of a recent single-arm trial (ZUMA-5) of axicabtagene ciloleucel (axi-cel) for relapsed/refractory (r/r) FL demonstrated high rates of durable response and tolerable toxicity among treated patients. To quantify the value of axi-cel compared to standard of care (SOC) to manage r/r FL patients who have had at least two prior lines of systemic therapy (3L+), a cost-effectiveness model was developed from a US third-party payer perspective. METHODS: A three-state partitioned survival cost-effectiveness model was developed with a lifetime horizon. Patient-level analyses of the 36-month ZUMA-5 (axi-cel) and SCHOLAR-5 (SOC) studies were used to extrapolate progression-free and overall survivals. After 5 years of survival, an estimated 40% of the modeled population was assumed to experience long-term remission based on literature. Results include the incremental cost-effectiveness ratio (ICER) measured as incremental cost per quality-adjusted life year (QALY) gained. One-way sensitivity analysis (OWSA), probabilistic sensitivity analysis (PSA), and scenario analyses were performed. All outcomes were discounted 3% per year. RESULTS: Axi-cel led to an increase of 4.28 life-years, 3.64 QALYs and a total cost increase of $321,192 relative to SOC, resulting in an ICER of $88,300 per QALY. Across all parameters varied in the OWSA, the ICER varied between $133,030 and $67,277. In the PSA, axi-cel had a 99% probability of being cost-effective across 5,000 iterations using a $150,000 willingness-to-pay threshold. CONCLUSIONS: Given the robustness of the model results and sensitivity analyses, axi-cel is expected to be a cost-effective treatment in 3L+ r/r FL.

Cost-effectiveness of rotavirus vaccination in children under five years of age in 195 countries: A meta-regression analysis.

BACKGROUND: Rotavirus caused an estimated 151,714 deaths from diarrhea among children under 5 in 2019. To reduce mortality, countries are considering adding rotavirus vaccination to their routine immunization program. Cost-effectiveness analyses (CEAs) to inform these decisions are not available in every setting, and where they are, results are sensitive to modeling assumptions, especially about vaccine efficacy. We used advances in meta-regression methods and estimates of vaccine efficacy by location to estimate incremental cost-effectiveness ratios (ICERs) for rotavirus vaccination in 195 countries. METHODS: Beginning with Tufts University CEA and Global Health CEA registries we used 515 ICERs from 68 articles published through 2017, extracted 938 additional one-way sensitivity analyses, and excluded 33 ICERs for a sample of 1,418. We used a five-stage, mixed-effects, Bayesian metaregression framework to predict ICERs, and logistic regression model to predict the probability that the vaccine was cost-saving. For both models, covariates were vaccine characteristics including efficacy, study methods, and country-specific rotavirus disability-adjusted life-years (DALYs) and gross domestic product (GDP) per capita. All results are reported in 2017 United States dollars. RESULTS: Vaccine efficacy, vaccine cost, GDP per capita and rotavirus DALYs were important drivers of variability in ICERs. Globally, the median ICER was $2,289 (95% uncertainty interval (UI): $147-$38,993) and ranged from $85 per DALY averted (95% UI: $13-$302) in Central African Republic to $70,599 per DALY averted (95% UI: $11,030-$263,858) in the United States. Among countries eligible for support from Gavi, The Vaccine Alliance, the mean ICER was $255 per DALY averted (95% UI: $39-$918), and among countries eligible for the PAHO revolving fund, the mean ICER was $2,464 per DALY averted (95% UI: $382-$3,118). CONCLUSION: Our findings incorporate recent evidence that vaccine efficacy differs across locations, and support expansion of rotavirus vaccination programs, particularly in countries eligible for support from Gavi, The Vaccine Alliance.

Cost-effectiveness of HPV vaccination in 195 countries: A meta-regression analysis.

Cost-effectiveness analysis (CEA) is a well-known, but resource intensive, method for comparing the costs and health outcomes of health interventions. To build on available evidence, researchers are developing methods to transfer CEA across settings; previous methods do not use all available results nor quantify differences across settings. We conducted a meta-regression analysis of published CEAs of human papillomavirus (HPV) vaccination to quantify the effects of factors at the country, intervention, and method-level, and predict incremental cost-effectiveness ratios (ICERs) for HPV vaccination in 195 countries. We used 613 ICERs reported in 75 studies from the Tufts University's Cost-Effectiveness Analysis (CEA) Registry and the Global Health CEA Registry, and extracted an additional 1,215 one-way sensitivity analyses. A five-stage, mixed-effects meta-regression framework was used to predict country-specific ICERs. The probability that HPV vaccination is cost-saving in each country was predicted using a logistic regression model. Covariates for both models included methods and intervention characteristics, and each country's cervical cancer burden and gross domestic product per capita. ICERs are positively related to vaccine cost, and negatively related to cervical cancer burden. The mean predicted ICER for HPV vaccination is 2017 US$4,217 per DALY averted (95% uncertainty interval (UI): US$773-13,448) globally, and below US$800 per DALY averted in 64 countries. Predicted ICERs are lowest in Sub-Saharan Africa and South Asia, with a population-weighted mean ICER across 46 countries of US$706 per DALY averted (95% UI: $130-2,245), and across five countries of US$489 per DALY averted (95% UI: $90-1,557), respectively. Meta-regression analyses can be conducted on CEA, where one-way sensitivity analyses are used to quantify the effects of factors at the intervention and method-level. Building on all published results, our predictions support introducing and expanding HPV vaccination, especially in countries that are eligible for subsidized vaccines from GAVI, the Vaccine Alliance, and Pan American Health Organization.

Modelling the potential cost-effectiveness of food-based programs to reduce malnutrition.

Poor quality diets contribute to malnutrition globally, but evidence is weak on the cost-effectiveness of food-based interventions that shift diets. This study assessed 11 candidate interventions developed through Delphi techniques to improve diets in India, Nigeria, and Ethiopia. A Markov simulation model incorporated time, individual-level, nutrition, and policy parameters to estimate health impacts and cost-effectiveness for reducing stunting, anaemia, diarrhea, and mortality in preschool children. At an assumed 80% coverage, interventions considered would potentially save between 0·16 and 3·20 years of life per child. The average cost-effectiveness ratio ranged from US$9 to US$2000 per life year saved. This approach, linking expert knowledge, known costs, and modelling, offers potential for estimating cost-effective investments for better informed policy choice where empirical evidence is limited.

Comparative risk assessment of school food environment policies and childhood diets, childhood obesity, and future cardiometabolic mortality in the United States.

BACKGROUND: Promising school policies to improve children's diets include providing fresh fruits and vegetables (F&V) and competitive food restrictions on sugar-sweetened beverages (SSBs), yet the impact of national implementation of these policies in US schools on cardiometabolic disease (CMD) risk factors and outcomes is not known. Our objective was to estimate the impact of national implementation of F&V provision and SSB restriction in US elementary, middle, and high schools on dietary intake and body mass index (BMI) in children and future CMD mortality. METHODS: We used comparative risk assessment (CRA) frameworks to model the impacts of these policies with input parameters from nationally representative surveys, randomized-controlled trials, and systematic reviews and meta-analyses. For children ages 5-18 years, this incorporated national data on current dietary intakes and BMI, impacts of these policies on diet, and estimated effects of dietary changes on BMI. In adults ages 25 and older, we further incorporated the sustainability of dietary changes to adulthood, effects of dietary changes on CMD, and national CMD death statistics, modeling effects if these policies had been in place when current US adults were children. Uncertainty across inputs was incorporated using 1000 Monte Carlo simulations. RESULTS: National F&V provision would increase daily fruit intake in children by as much as 25.0% (95% uncertainty interval (UI): 15.4, 37.7%), and would have small effects on vegetable intake. SSB restriction would decrease daily SSB intake by as much as 26.5% (95% UI: 6.4, 46.4%), and reduce BMI by as much as 0.7% (95% UI: 0.2, 1.2%). If F&V provision and SSB restriction were nationally implemented, an estimated 22,383 CMD deaths/year (95% UI: 18735, 25930) would be averted. CONCLUSION: National school F&V provision and SSB restriction policies implemented in elementary, middle, and high schools could improve diet and BMI in children and reduce CMD mortality later in life.

Designing programs to improve diets for maternal and child health: estimating costs and potential dietary impacts of nutrition-sensitive programs in Ethiopia, Nigeria, and India.

Improving maternal and child nutrition in resource-poor settings requires effective use of limited resources, but priority-setting is constrained by limited information about program costs and impacts, especially for interventions designed to improve diet quality. This study utilized a mixed methods approach to identify, describe and estimate the potential costs and impacts on child dietary intake of 12 nutrition-sensitive programs in Ethiopia, Nigeria and India. These potential interventions included conditional livestock and cash transfers, media and education, complementary food processing and sales, household production and food pricing programs. Components and costs of each program were identified through a novel participatory process of expert regional consultation followed by validation and calibration from literature searches and comparison with actual budgets. Impacts on child diets were determined by estimating of the magnitude of economic mechanisms for dietary change, comprehensive reviews of evaluations and effectiveness for similar programs, and demographic data on each country. Across the 12 programs, total cost per child reached (net present value, purchasing power parity adjusted) ranged very widely: from 0.58 to 2650 USD/year among five programs in Ethiopia; 2.62 to 1919 USD/year among four programs in Nigeria; and 27 to 586 USD/year among three programs in India. When impacts were assessed, the largest dietary improvements were for iron and zinc intakes from a complementary food production program in Ethiopia (increases of 17.7 mg iron/child/day and 7.4 mg zinc/child/day), vitamin A intake from a household animal and horticulture production program in Nigeria (335 RAE/child/day), and animal protein intake from a complementary food processing program in Nigeria (20.0 g/child/day). These results add substantial value to the limited literature on the costs and dietary impacts of nutrition-sensitive interventions targeting children in resource-limited settings, informing policy discussions and serving as critical inputs to future cost-effectiveness analyses focusing on disease outcomes.

The value of point-of-care CD4+ and laboratory viral load in tailoring antiretroviral therapy monitoring strategies to resource limitations.

OBJECTIVE: To examine the clinical and economic value of point-of-care CD4 (POC-CD4) or viral load monitoring compared with current practices in Mozambique, a country representative of the diverse resource limitations encountered by HIV treatment programs in sub-Saharan Africa. DESIGN/METHODS: We use the Cost-Effectiveness of Preventing AIDS Complications-International model to examine the clinical impact, cost (2014 US$), and incremental cost-effectiveness ratio [$/year of life saved (YLS)] of ART monitoring strategies in Mozambique. We compare: monitoring for clinical disease progression [clinical ART monitoring strategy (CLIN)] vs. annual POC-CD4 in rural settings without laboratory services and biannual laboratory CD4 (LAB-CD4), biannual POC-CD4, and annual viral load in urban settings with laboratory services. We examine the impact of a range of values in sensitivity analyses, using Mozambique's 2014 per capita gross domestic product ($620) as a benchmark cost-effectiveness threshold. RESULTS: In rural settings, annual POC-CD4 compared to CLIN improves life expectancy by 2.8 years, reduces time on failed ART by 0.6 years, and yields an incremental cost-effectiveness ratio of $480/YLS. In urban settings, biannual POC-CD4 is more expensive and less effective than viral load. Compared to biannual LAB-CD4, viral load improves life expectancy by 0.6 years, reduces time on failed ART by 1.0 year, and is cost-effective ($440/YLS). CONCLUSION: In rural settings, annual POC-CD4 improves clinical outcomes and is cost-effective compared to CLIN. In urban settings, viral load has the greatest clinical benefit and is cost-effective compared to biannual POC-CD4 or LAB-CD4. Tailoring ART monitoring strategies to specific settings with different available resources can improve clinical outcomes while remaining economically efficient.

The HIV Cure Research Agenda: The Role of Mathematical Modelling and Cost-Effectiveness Analysis.

The research agenda towards an HIV cure is building rapidly. In this article, we discuss the reasons for and methodological approach to using mathematical modeling and cost-effectiveness analysis in this agenda. We provide a brief description of the proof of concept for cure and the current directions of cure research. We then review the types of clinical economic evaluations, including cost analysis, cost-benefit analysis, and cost-effectiveness analysis. We describe the use of mathematical modeling and cost-effectiveness analysis early in the HIV epidemic as well as in the era of combination antiretroviral therapy. We then highlight the novel methodology of Value of Information analysis and its potential role in the planning of clinical trials. We close with recommendations for modeling and cost-effectiveness analysis in the HIV cure agenda.