Person:

Resch, Stephen

Background: Despite the existence of effective drug treatments, tuberculosis (TB) causes 2 million deaths annually worldwide. Effective treatment is complicated by multidrug-resistant TB (MDR TB) strains that respond only to second-line drugs. We projected the health benefits and cost-effectiveness of using drug susceptibility testing and second-line drugs in a lower-middle-income setting with high levels of MDR TB. Methods and Findings: We developed a dynamic state-transition model of TB. In a base case analysis, the model was calibrated to approximate the TB epidemic in Peru, a setting with a smear-positive TB incidence of 120 per 100,000 and 4.5% MDR TB among prevalent cases. Secondary analyses considered other settings. The following strategies were evaluated: first-line drugs administered under directly observed therapy (DOTS), locally standardized second-line drugs for previously treated cases (STR1), locally standardized second-line drugs for previously treated cases with test-confirmed MDR TB (STR2), comprehensive drug susceptibility testing and individualized treatment for previously treated cases (ITR1), and comprehensive drug susceptibility testing and individualized treatment for all cases (ITR2). Outcomes were costs per TB death averted and costs per quality-adjusted life year (QALY) gained. We found that strategies incorporating the use of second-line drug regimens following first-line treatment failure were highly cost-effective compared to strategies using first-line drugs only. In our base case, standardized second-line treatment for confirmed MDR TB cases (STR2) had an incremental cost-effectiveness ratio of $720 per QALY ($8,700 per averted death) compared to DOTS. Individualized second-line drug treatment for MDR TB following first-line failure (ITR1) provided more benefit at an incremental cost of $990 per QALY ($12,000 per averted death) compared to STR2. A more aggressive version of the individualized treatment strategy (ITR2), in which both new and previously treated cases are tested for MDR TB, had an incremental cost-effectiveness ratio of $11,000 per QALY ($160,000 per averted death) compared to ITR1. The STR2 and ITR1 strategies remained cost-effective under a wide range of alternative assumptions about treatment costs, effectiveness, MDR TB prevalence, and transmission. Conclusions: Treatment of MDR TB using second-line drugs is highly cost-effective in Peru. In other settings, the attractiveness of strategies using second-line drugs will depend on TB incidence, MDR burden, and the available budget, but simulation results suggest that individualized regimens would be cost-effective in a wide range of situations.

Background: In resource-limited settings, HIV budgets are flattening or decreasing. A policy of discontinuing antiretroviral therapy (ART) after HIV treatment failure was modeled to highlight trade-offs among competing policy goals of optimizing individual and population health outcomes. Methods: In settings with two available ART regimens, we assessed two strategies: (1) continue ART after second-line failure (Status Quo) and (2) discontinue ART after second-line failure (Alternative). A computer model simulated outcomes for a single cohort of newly detected, HIV-infected individuals. Projections were fed into a population-level model allowing multiple cohorts to compete for ART with constraints on treatment capacity. In the Alternative strategy, discontinuation of second-line ART occurred upon detection of antiretroviral failure, specified by WHO guidelines. Those discontinuing failed ART experienced an increased risk of AIDS-related mortality compared to those continuing ART. Results: At the population level, the Alternative strategy increased the mean number initiating ART annually by 1,100 individuals (+18.7%) to 6,980 compared to the Status Quo. More individuals initiating ART under the Alternative strategy increased total life-years by 15,000 (+2.8%) to 555,000, compared to the Status Quo. Although more individuals received treatment under the Alternative strategy, life expectancy for those treated decreased by 0.7 years (−8.0%) to 8.1 years compared to the Status Quo. In a cohort of treated patients only, 600 more individuals (+27.1%) died by 5 years under the Alternative strategy compared to the Status Quo. Results were sensitive to the timing of detection of ART failure, number of ART regimens, and treatment capacity. Although we believe the results robust in the short-term, this analysis reflects settings where HIV case detection occurs late in the disease course and treatment capacity and the incidence of newly detected patients are stable. Conclusions: In settings with inadequate HIV treatment availability, trade-offs emerge between maximizing outcomes for individual patients already on treatment and ensuring access to treatment for all people who may benefit. While individuals may derive some benefit from ART even after virologic failure, the aggregate public health benefit is maximized by providing effective therapy to the greatest number of people. These trade-offs should be explicit and transparent in antiretroviral policy decisions.

Background: Women in Nigeria face some of the highest maternal mortality risks in the world. We explore the benefits and cost-effectiveness of individual and integrated packages of interventions to prevent pregnancy-related deaths. Methods: We adapt a previously validated maternal mortality model to Nigeria. Model outcomes included clinical events, population measures, costs, and cost-effectiveness ratios. Separate models were adapted to Southwest and Northeast zones using survey-based data. Strategies consisted of improving coverage of effective interventions, and could include improved logistics. Results: Increasing family planning was the most effective individual intervention to reduce pregnancy-related mortality, was cost saving in the Southwest zone and cost-effective elsewhere, and prevented nearly 1 in 5 abortion-related deaths. However, with a singular focus on family planning and safe abortion, mortality reduction would plateau below MDG 5. Strategies that could prevent 4 out of 5 maternal deaths included an integrated and stepwise approach that includes increased skilled deliveries, facility births, access to antenatal/postpartum care, improved recognition of referral need, transport, and availability quality of EmOC in addition to family planning and safe abortion. The economic benefits of these strategies ranged from being cost-saving to having incremental cost-effectiveness ratios less than $500 per YLS, well below Nigeria’s per capita GDP. Conclusions: Early intensive efforts to improve family planning and control of fertility choices, accompanied by a stepwise effort to scale-up capacity for integrated maternal health services over several years, will save lives and provide equal or greater value than many public health interventions we consider among the most cost-effective (e.g., childhood immunization).

Low- and middle-income countries need to consider economic issues such as cost-effectiveness, affordability and sustainability before introducing a program for human papillomavirus (HPV) vaccination. However, many such countries lack the technical capacity and data to conduct their own analyses. Analysts informing policy decisions should address the following questions: 1) Is an economic analysis needed? 2) Should analyses address costs, epidemiological outcomes, or both? 3) If costs are considered, what sort of analysis is needed? 4) If outcomes are considered, what sort of model should be used? 5) How complex should the analysis be? 6) How should uncertainty be captured? 7) How should model results be communicated? Selecting the appropriate analysis is essential to ensure that all the important features of the decision problem are correctly represented, but that the analyses are not more complex than necessary. This report describes the consensus of an expert group convened by the World Health Organization, prioritizing key issues to be addressed when considering economic analyses to support HPV vaccine introduction in these countries.

Background: As part of efforts to reduce maternal deaths in Nigeria, pregnant women are being encouraged to give birth in healthcare facilities. However, little is known about whether or not available healthcare facilities can cope with an increasing demand for obstetric care. We thus carried out this survey as a rapid and tactical assessment of facility quality. We visited 121 healthcare facilities, and used the opportunity to interview over 700 women seeking care at these facilities. Findings Most of the primary healthcare facilities we visited were unable to provide all basic Emergency Obstetric Care (bEmOC) services. In general, they lack clinical staff needed to dispense maternal and neonatal care services, ambulances and uninterrupted electricity supply whenever there were obstetric emergencies. Secondary healthcare facilities fared better, but, like their primary counterparts, lack neonatal care infrastructure. Among patients, most lived within 30 minutes of the visited facilities and still reported some difficulty getting there. Of those who had had two or more childbirths, the conditional probability of a delivery occurring in a healthcare facility was 0.91 if the previous delivery occurred in a healthcare facility, and 0.24 if it occurred at home. The crude risk of an adverse neonatal outcome did not significantly vary by delivery site or birth attendant, and the occurrence of such an outcome during an in-facility delivery may influence the mother to have her next delivery outside. Such an outcome during a home delivery may not prompt a subsequent in-facility delivery. Conclusions: In conclusion, reducing maternal deaths in Nigeria will require attention to both increasing the number of facilities with high-quality EmOC capability and also assuring Nigerian women have access to these facilities regardless of where they live.

Background: Point-of-care CD4 tests at HIV diagnosis could improve linkage to care in resource-limited settings. Our objective is to evaluate the clinical and economic impact of point-of-care CD4 tests compared to laboratory-based tests in Mozambique. Methods and Findings: We use a validated model of HIV testing, linkage, and treatment (CEPAC-International) to examine two strategies of immunological staging in Mozambique: (1) laboratory-based CD4 testing (LAB-CD4) and (2) point-of-care CD4 testing (POC-CD4). Model outcomes include 5-y survival, life expectancy, lifetime costs, and incremental cost-effectiveness ratios (ICERs). Input parameters include linkage to care (LAB-CD4, 34%; POC-CD4, 61%), probability of correctly detecting antiretroviral therapy (ART) eligibility (sensitivity: LAB-CD4, 100%; POC-CD4, 90%) or ART ineligibility (specificity: LAB-CD4, 100%; POC-CD4, 85%), and test cost (LAB-CD4, US$10; POC-CD4, US$24). In sensitivity analyses, we vary POC-CD4-specific parameters, as well as cohort and setting parameters to reflect a range of scenarios in sub-Saharan Africa. We consider ICERs less than three times the per capita gross domestic product in Mozambique (US$570) to be cost-effective, and ICERs less than one times the per capita gross domestic product in Mozambique to be very cost-effective. Projected 5-y survival in HIV-infected persons with LAB-CD4 is 60.9% (95% CI, 60.9%–61.0%), increasing to 65.0% (95% CI, 64.9%–65.1%) with POC-CD4. Discounted life expectancy and per person lifetime costs with LAB-CD4 are 9.6 y (95% CI, 9.6–9.6 y) and US$2,440 (95% CI, US$2,440–US$2,450) and increase with POC-CD4 to 10.3 y (95% CI, 10.3–10.3 y) and US$2,800 (95% CI, US$2,790–US$2,800); the ICER of POC-CD4 compared to LAB-CD4 is US$500/year of life saved (YLS) (95% CI, US$480–US$520/YLS). POC-CD4 improves clinical outcomes and remains near the very cost-effective threshold in sensitivity analyses, even if point-of-care CD4 tests have lower sensitivity/specificity and higher cost than published values. In other resource-limited settings with fewer opportunities to access care, POC-CD4 has a greater impact on clinical outcomes and remains cost-effective compared to LAB-CD4. Limitations of the analysis include the uncertainty around input parameters, which is examined in sensitivity analyses. The potential added benefits due to decreased transmission are excluded; their inclusion would likely further increase the value of POC-CD4 compared to LAB-CD4. Conclusions: POC-CD4 at the time of HIV diagnosis could improve survival and be cost-effective compared to LAB-CD4 in Mozambique, if it improves linkage to care. POC-CD4 could have the greatest impact on mortality in settings where resources for HIV testing and linkage are most limited. Please see later in the article for the Editors' Summary

Background: Pediatric antiretroviral therapy (ART) has been shown to substantially reduce morbidity and mortality in HIV-infected infants and children. To accurately project program costs, analysts need accurate estimations of antiretroviral drug (ARV) costs for children. However, the costing of pediatric antiretroviral therapy is complicated by weight-based dosing recommendations which change as children grow. Methods: We developed a step-by-step methodology for estimating the cost of pediatric ARV regimens for children ages 0–13 years old. The costing approach incorporates weight-based dosing recommendations to provide estimated ARV doses throughout childhood development. Published unit drug costs are then used to calculate average monthly drug costs. We compared our derived monthly ARV costs to published estimates to assess the accuracy of our methodology. Results: The estimates of monthly ARV costs are provided for six commonly used first-line pediatric ARV regimens, considering three possible care scenarios. The costs derived in our analysis for children were fairly comparable to or slightly higher than available published ARV drug or regimen estimates. Conclusions: The methodology described here can be used to provide an accurate estimation of pediatric ARV regimen costs for cost-effectiveness analysts to project the optimum packages of care for HIV-infected children, as well as for program administrators and budget analysts who wish to assess the feasibility of increasing pediatric ART availability in constrained budget environments.

Background: Development of new, effective, and affordable tuberculosis (TB) therapies has been identified as a critical priority for global TB control. As new candidates emerge from the global TB drug pipeline, the potential impacts of novel, shorter regimens on TB incidence and mortality have not yet been examined. Methods and Findings: We used a mathematical model of TB to evaluate the expected benefits of shortening the duration of effective chemotherapy for active pulmonary TB. First, we considered general relationships between treatment duration and TB dynamics. Next, as a specific example, we calibrated the model to reflect the current situation in the South-East Asia region. We found that even with continued and rapid progress in scaling up the World Health Organization's DOTS strategy of directly observed, short-course chemotherapy, the benefits of reducing treatment duration would be substantial. Compared to a baseline of continuing DOTS coverage at current levels, and with currently available tools, a 2-mo regimen introduced by 2012 could prevent around 20% (range 13%–28%) of new cases and 25% (range 19%–29%) of TB deaths in South-East Asia between 2012 and 2030. If effective treatment with existing drugs expands rapidly, overall incremental benefits of shorter regimens would be lower, but would remain considerable (13% [range 8%–19%] and 19% [range 15%–23%] reductions in incidence and mortality, respectively, between 2012 and 2030). A ten-year delay in the introduction of new drugs would erase nearly three-fourths of the total expected benefits in this region through 2030. Conclusions: The introduction of new, shorter treatment regimens could dramatically accelerate the reductions in TB incidence and mortality that are expected under current regimens—with up to 2- or 3-fold increases in rates of decline if shorter regimens are accompanied by enhanced case detection. Continued progress in reducing the global TB burden will require a balanced approach to pursuing new technologies while promoting wider implementation of proven strategies.

Background: State-level estimates from the Centers for Disease Control and Prevention (CDC) underestimate the obesity epidemic because they use self-reported height and weight. We describe a novel bias-correction method and produce corrected state-level estimates of obesity and severe obesity. Methods: Using non-parametric statistical matching, we adjusted self-reported data from the Behavioral Risk Factor Surveillance System (BRFSS) 2013 (n = 386,795) using measured data from the National Health and Nutrition Examination Survey (NHANES) (n = 16,924). We validated our national estimates against NHANES and estimated bias-corrected state-specific prevalence of obesity (BMI≥30) and severe obesity (BMI≥35). We compared these results with previous adjustment methods. Results: Compared to NHANES, self-reported BRFSS data underestimated national prevalence of obesity by 16% (28.67% vs 34.01%), and severe obesity by 23% (11.03% vs 14.26%). Our method was not significantly different from NHANES for obesity or severe obesity, while previous methods underestimated both. Only four states had a corrected obesity prevalence below 30%, with four exceeding 40%–in contrast, most states were below 30% in CDC maps. Conclusions: Twelve million adults with obesity (including 6.7 million with severe obesity) were misclassified by CDC state-level estimates. Previous bias-correction methods also resulted in underestimates. Accurate state-level estimates are necessary to plan for resources to address the obesity epidemic.

Background: Cervical cancer is the fourth leading cause of cancer death in women, with 85% of cases and deaths occurring in developing countries. While organized screening programs have reduced cervical cancer incidence in high-income countries through detection and treatment of precancerous lesions, the implementation of organized screening has not been effective in low-resource settings due to lack of infrastructure and limited budgets. Our objective was to estimate the cost of comprehensive primary and secondary cervical cancer prevention in low- and middle-income countries. Methods and Findings: We performed a modeling analysis to estimate 1) for girls aged 10 years, the cost of 2-dose human papillomavirus (HPV) vaccination; and 2) for women aged 30 to 49 years, the cost of cervical cancer screening (with visual inspection with acetic acid (VIA), HPV testing, or cytology) and preventive treatment in 102 low- and middle-income countries from 2015 to 2024. We used an Excel-based costing and service utilization model to estimate financial costs (2013 US$) based on prevalence of HPV, prevalence of precancerous lesions, and screening test performance. Where epidemiologic data were unavailable, we extrapolated from settings with data using an individual-based microsimulation model of cervical carcinogenesis (calibrated to 20 settings) and multivariate regression. Total HPV vaccination costs ranged from US$8.6 billion to US$24.2 billion for all scenarios considered (immediate, 5-year, or 10-year roll-out; price per dose US$4.55-US$70 by country income level). The total cost of screening and preventive treatment ranged from US$5.1 billion (10-year roll-out, screening once at age 35 years) to US$42.3 billion (immediate roll-out, high intensity screening). Limitations of this analysis include the assumption of standardized protocols by country income level that did not account for the potential presence of multiple screening modalities or management strategies within a country, and extrapolation of cost and epidemiologic data to settings where data were limited. Conclusions: The estimated cost of comprehensive cervical cancer prevention with 2-dose HPV vaccination of 10-year-old girls and screening of women aged 30 to 49 years ranges from US$13.7 billion to US$66.5 billion, depending on speed of roll-out, vaccine price per dose, and screening test and frequency. Findings demonstrate the substantial impact of vaccine price in middle-income countries that are not eligible for assistance from Gavi, the Vaccine Alliance. Replacing routine cytology with HPV-based screening may reduce total costs. Data on the health impact and relative cost-effectiveness of strategies are needed to determine the best value for public health dollars.