A. David Paltiel

Conventional value-of-information (VOI) analysis bases decisions on a composite cost-effectiveness measure that aggregates clinical and cost outcomes. We sought to highlight potentially informative tradeoffs by estimating and reporting the "disaggregated" components, allowing stakeholders-such as clinicians, patients, trial funders, policymakers, and trial networks-to identify what drives the value of additional research. We used a microsimulation to project the value of a hypothetical trial comparing mortality associated with different tuberculosis screening strategies among hospitalized patients with human immunodeficiency virus (HIV) in South Africa. Apart from expressing VOI as conventional, "aggregated" net monetary benefit (NMB), we assessed "disaggregated" outcomes that contribute to NMB calculations: tuberculosis cases detected, deaths, life-years, and healthcare costs associated with trial-informed decisions. We varied key parameters in probabilistic sensitivity analysis. We considered two willingness-to-pay thresholds: US $3000/year of life saved (YLS) (~50% of South Africa's per-capita gross domestic product [GDP]); and $780/YLS, the willingness-to-pay value where decision uncertainty is highest, per the baseline analysis. At willingness to pay = $3000/YLS, implementing the post-trial optimal strategy would produce favorable incremental NMB ($654.3 million) and better clinical outcomes (57,000 additional tuberculosis cases detected, 16,000 fewer deaths, and 294,000 more life-years), but it would incur an additional $37.4 million in healthcare costs over 5 years. At willingness to pay = $780/YLS, implementing the post-trial optimal strategy would yield positive incremental NMB of $2.5 million while lowering healthcare costs by $11 million, but it would produce worse clinical outcomes: 18,000 fewer tuberculosis cases detected, 6,000 additional deaths, and 80,000 fewer life-years. Though a trial may yield positive NMB in conventional VOI analysis owing to expected cost savings, some clinical outcomes might be unfavorable. To better inform priorities, VOI studies should include disaggregated outcomes alongside aggregated NMB.

Glucagon-like peptide-1 receptor agonists (GLP1RAs) lead to substantial weight loss and pain reduction in persons with knee osteoarthritis and obesity. To evaluate the cost-effectiveness of 2 GLP1RAs, semaglutide and tirzepatide, for patients with osteoarthritis and obesity. Osteoarthritis Policy Model, a validated microsimulation model of knee osteoarthritis, to estimate lifetime benefits and costs of weight loss strategies. Published data to derive treatment-related weight loss, pain reduction, and costs of GLP1RAs from the U.S. Office of Health Policy. Persons with knee osteoarthritis and obesity in the United States. The base-case cohort had a Western Ontario and McMaster Universities Osteoarthritis Index pain score of 71 (0 to 100, 100 worst) and a mean body mass index (BMI) of 40 kg/m². Lifetime. Health care, societal. Semaglutide, tirzepatide, laparoscopic sleeve gastrectomy (LSG), Roux-en-Y gastric bypass (RYGB), and diet and exercise. Quality-adjusted life-years (QALYs), cost, and incremental cost-effectiveness ratios (ICERs). Tirzepatide provided greater health benefits at lower costs than semaglutide and yielded a $57 400 per QALY ICER versus diet and exercise. For those eligible, RYGB provided greater health benefits at lower costs than the 2 GLP1RAs and had a $30 700 per QALY ICER versus LSG. Tirzepatide's ICER was most sensitive to changes in medication costs, treatment efficacy, and cohort baseline BMI. Tirzepatide had a 64% and semaglutide had a 34% probability of being cost-effective at a $100 000 per QALY threshold. Data from multiple sources. Both tirzepatide and semaglutide would be widely considered cost-effective when compared directly with usual care. Tirzepatide would offer the most favorable return on investment to decision makers whose cost-effectiveness thresholds exceed $57 400 per QALY. The Arthritis Foundation and National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Rotavirus is the leading cause of severe diarrhea among children under five worldwide, especially in low- and middle-income countries (LMICs). Although vaccination is the best strategy to prevent rotavirus, obstacles leading to poor vaccine effectiveness undermine its impact in LMICs. This study aimed to identify the optimal rotavirus vaccination strategy for Malawi by modeling vaccine impact and cost-effectiveness, comparing the current two-dose Rotarix vaccine schedule to two alternative vaccine delivery schedules and a next-generation neonatal vaccine (RV3-BB) from 2025-2034. The cost-effectiveness of rotavirus vaccine strategies in Malawi was evaluated from the government and societal perspectives using estimates of moderate-to-severe and non-severe rotavirus cases derived from a transmission dynamic model of rotavirus and published estimates of health-seeking behaviors and costs as inputs. A probabilistic sensitivity analysis was performed to evaluate the robustness of our results to parameter uncertainty. Over a ten-year time horizon, the current two-dose Rotarix strategy is predicted to avert over 1.5 million cases and 90,000 disability-adjusted life-years (DALYs) compared to no vaccination and is cost-effective at willingness-to-pay (WTP) thresholds above $105 per DALY averted from the government perspective. Adding a third dose at 14 weeks could avert an additional 1 million cases and 38,000 DALYs, while switching to the neonatal RV3-BB vaccine could avert 1.1 million cases and 41,000 DALYs compared to the current strategy. Whereas adding a third dose of Rotarix would cost $4.1-4.9 million, switching to the neonatal vaccine is expected to save $3.7 million compared to the current strategy. Considering the neonatal vaccine is not yet available, adding a third dose of Rotarix at 14 weeks of age is cost-effective at WTP thresholds above $138 per DALY averted. The neonatal vaccine offers a more cost-effective alternative to Malawi’s current rotavirus vaccine, while adding a third dose to the current strategy also provides substantial benefits.

Future U.S. congressional funding for the President's Emergency Plan for AIDS Relief (PEPFAR) program is uncertain. To evaluate the clinical and economic impacts of abruptly scaling back PEPFAR funding ($460 million) from South Africa's total HIV budget ($2.56 billion) in 2024. Model-based analysis of 100%, 50%, and 0% PEPFAR funding with proportional decreases in HIV diagnosis rates (26.0, 24.3, 22.6 per 100 person-years [PY]), 1-year treatment engagement (people with HIV [PWH] receiving/initiating antiretroviral therapy: 92.2%/80.4%, 87.1%/76.0%, 82.0%/71.5%), and primary prevention (4.0%, 2.2%, 0.5% reduction in incidence with no programming [1.24 per 100 PY]). Published HIV care continuum; PEPFAR funding estimates. South African adults (HIV prevalence, 16.2%; incidence, 0.32 per 100 PY). Lifetime. Health care sector. PEPFAR funded 100% (PEPFAR_100%), 50% (PEPFAR_50%), or 0% (PEPFAR_0%). HIV infections, life expectancy, and lifetime costs (2023 U.S. dollars). With current HIV programming (PEPFAR_100%), 1 190 000 new infections are projected over 10 years; life expectancy would be 61.42 years for PWH, with lifetime costs of $11 180 per PWH. Reduced PEPFAR funding (PEPFAR_50% and PEPFAR_0%) would add 286 000 and 565 000 new infections, respectively. PWH would lose 2.02 and 3.71 life-years with nominal lifetime cost reductions of $620 per PWH and $1140 per PWH that would be offset at the population level by more PWH requiring treatment for infection. Countries with similar HIV prevalence and greater reliance on PEPFAR funding could experience disproportionately higher incremental infections and survival losses. Budget fungibility and exact programmatic implications of reducing PEPFAR funding are unknown. Abrupt PEPFAR cutbacks would have immediate and long-term detrimental effects on epidemiologic and clinical HIV outcomes in South Africa. National Institutes of Health.

Rotavirus is the leading cause of severe diarrhea among children under five worldwide, especially in low- and middle-income countries (LMICs). Although vaccination is the best strategy for preventing rotavirus infection, obstacles leading to poor vaccine effectiveness undermine its impact in LMICs. This study aimed to evaluate the impact and cost-effectiveness of the current two-dose Rotarix vaccine schedule in Malawi compared to two alternative vaccine delivery schedules and a next-generation neonatal vaccine (RV3-BB) from 2025-2034. The cost-effectiveness of rotavirus vaccine strategies in Malawi was evaluated from both the government and societal perspectives using estimates of moderate-to-severe and non-severe rotavirus cases derived from a mathematical model of rotavirus transmission dynamics and published estimates of health-seeking behaviors and costs as inputs. A probabilistic sensitivity analysis was performed to evaluate the robustness of our results to parameter uncertainty. Over a ten-year time horizon, the current two-dose strategy was predicted to avert over 1.5 million cases and 90,000 disability-adjusted life-years (DALYs) and cost $104.87 per DALY averted compared to no vaccination from the government perspective. Adding a third dose at 14 weeks could avert about 1 million more cases and cost $5 million more than the current strategy. The neonatal RV3-BB vaccine could avert 1.1 million cases and 41,000 DALYs due to rotavirus and save about $3.7 million compared to the current strategy. The current rotavirus vaccine program in Malawi is cost-effective and saves lives compared to no vaccination. However, adding a third dose is likely to be cost-effective at a willingness to pay (WTP) of $138.38 per DALY averted, while switching to the neonatal RV3-BB vaccine when available is likely to be cost-effective at a WTP above $45.89 per DALY averted.

Background: Although prior studies of tuberculosis-preventive treatment (TPT) for pregnant people with human immunodeficiency virus (PPWH) report conflicting adverse pregnancy outcome (APO) risks, international guidelines recommend TPT for PPWH. Methods: We used a microsimulation model to evaluate 5 TPT strategies among PPWH receiving antiretroviral therapy in South Africa: No TPT; 6 months of isoniazid (6H) or 3 months of isoniazid-rifapentine (3HP) during pregnancy (Immediate 6H or Immediate 3HP) or post partum (Deferred 6H or Deferred 3HP). The primary outcomes were maternal, fetal/infant, and combined deaths from causes potentially influenced by TPT (maternal tuberculosis, maternal hepatotoxicity, stillbirth, low birth weight [LBW], and infant tuberculosis). Tuberculosis during pregnancy confers 250% and 81% higher modeled risks of stillbirth and LBW, respectively. In lower-risk or higher-risk scenarios, immediate TPT confers 38% lower or 92% higher risks of stillbirth and 16% lower or 35% higher risks of LBW. Results: Immediate TPT would minimize deaths among PPWH. When TPT confers higher stillbirth and LBW risks, immediate TPT would produce the most combined maternal and fetal/infant deaths, even with low maternal CD4 cell count and high tuberculosis incidence. If immediate TPT yields a <4% or <20% increase in stillbirth or LBW, immediate TPT would produce fewer combined deaths than deferred TPT (sensitivity analysis range, <2%–22% and <11%–120%, respectively). Conclusions: If APO risks are below identifiable thresholds, TPT during pregnancy could decrease combined maternal and fetal/infant deaths. Given uncertainty around isoniazid's risks, and the low threshold at which APO risks could outweigh benefits from tuberculosis deaths averted, studies of newer TPT regimens among PPWH are warranted to inform guidelines.

Mobile testing services provide opportunities for active surveillance of infectious diseases for hard-to-reach and/or high-risk individuals who do not know their disease status. Identifying as many infected individuals as possible is important for mitigating disease transmission. Recently, multi-armed bandit sampling approaches have been adapted and applied in this setting to maximize the cumulative number of positive tests collected over time. However, these algorithms have not considered the possibility of variability in the number of tests administered across testing sites. What impact this variability has on the ability of these approaches to maximize yield is currently unknown. Therefore, we investigate this question by extending existing sampling frameworks to directly account for variability in testing volume while also maintaining the computational tractability of the previous methods. Through a simulation study based on human immunodeficiency virus infection characteristics in the Republic of the Congo (Congo-Brazzaville) as well as an application to COVID-19 testing data in Connecticut, we find improved long- and short-term performances of the new methods compared to several existing approaches. Based on these findings and the ease of computation, we recommend use of the newly developed methods for active surveillance of infectious diseases when variability in testing volume may be present.

There is a public health need to understand how different frequencies of COVID-19 booster vaccines may mitigate the risk of severe COVID-19, while accounting for waning of protection and differential risk by age and immune status. By analyzing United States COVID-19 surveillance and seroprevalence data in a microsimulation model, here we show that more frequent COVID-19 booster vaccination (every 6–12 months) in older age groups and the immunocompromised population would effectively reduce the burden of severe COVID-19, while frequent boosters in the younger population may only provide modest benefit against severe disease. In persons 75+ years, the model estimated that annual boosters would reduce absolute annual risk of severe COVID-19 by 199 (uncertainty interval: 183–232) cases per 100,000 persons, compared to a one-time booster vaccination. In contrast, for persons 18–49 years, the model estimated that annual boosters would reduce this risk by 14 (10–19) cases per 100,000 persons. Those with prior infection had lower benefit of more frequent boosting, and immunocompromised persons had larger benefit. Scenarios with emerging variants with immune evasion increased the benefit of more frequent variant-targeted boosters. This study underscores the benefit of considering key risk factors to inform frequency of COVID-19 booster vaccines in public health guidance and ensuring at least annual boosters in high-risk populations.