Estimated economic impact of vaccinations in 73 low- and middle-income countries, 2001-2020.

OBJECTIVE: To estimate the economic impact likely to be achieved by efforts to vaccinate against 10 vaccine-preventable diseases between 2001 and 2020 in 73 low- and middle-income countries largely supported by Gavi, the Vaccine Alliance. METHODS: We used health impact models to estimate the economic impact of achieving forecasted coverages for vaccination against Haemophilus influenzae type b, hepatitis B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, rotavirus, rubella, Streptococcus pneumoniae and yellow fever. In comparison with no vaccination, we modelled the costs - expressed in 2010 United States dollars (US$) - of averted treatment, transportation costs, productivity losses of caregivers and productivity losses due to disability and death. We used the value-of-a-life-year method to estimate the broader economic and social value of living longer, in better health, as a result of immunization. FINDINGS: We estimated that, in the 73 countries, vaccinations given between 2001 and 2020 will avert over 20 million deaths and save US$ 350 billion in cost of illness. The deaths and disability prevented by vaccinations given during the two decades will result in estimated lifelong productivity gains totalling US$ 330 billion and US$ 9 billion, respectively. Over the lifetimes of the vaccinated cohorts, the same vaccinations will save an estimated US$ 5 billion in treatment costs. The broader economic and social value of these vaccinations is estimated at US$ 820 billion. CONCLUSION: By preventing significant costs and potentially increasing economic productivity among some of the world's poorest countries, the impact of immunization goes well beyond health.

Gastric adenocarcinoma screening and prevention in the era of new biomarker and endoscopic technologies: a cost-effectiveness analysis.

OBJECTIVE: To estimate the cost-effectiveness of noncardia gastric adenocarcinoma (NCGA) screening strategies based on new biomarker and endoscopic technologies. DESIGN: Using an intestinal-type NCGA microsimulation model, we evaluated the following one-time screening strategies for US men: (1) serum pepsinogen to detect gastric atrophy (with endoscopic follow-up of positive screen results), (2) endoscopic screening to detect dysplasia and asymptomatic cancer (with endoscopic mucosal resection (EMR) treatment for detected lesions) and (3) Helicobacter pylori screening and treatment. Screening performance, treatment effectiveness, cancer and cost data were based on published literature and databases. Subgroups included current, former and never smokers. Outcomes included lifetime cancer risk and incremental cost-effectiveness ratios (ICERs), expressed as cost per quality-adjusted-life-year (QALY) gained. RESULTS: Screening the general population at age 50 years reduced the lifetime intestinal-type NCGA risk (0.24%) by 26.4% with serum pepsinogen screening, 21.2% with endoscopy and EMR and 0.2% with H. pylori screening/treatment. Targeting current smokers reduced the lifetime risk (0.35%) by 30.8%, 25.5%, and 0.1%, respectively. For all subgroups, serum pepsinogen screening was more effective and more cost-effective than all other strategies, although its ICER varied from $76,000/QALY (current smokers) to $105,400/QALY (general population). Results were sensitive to H. pylori prevalence, screen age and serum pepsinogen test sensitivity. Probabilistic sensitivity analysis found that at a $100,000/QALY willingness-to-pay threshold, the probability that serum pepsinogen screening was preferred was 0.97 for current smokers. CONCLUSIONS: Although not warranted for the general population, targeting high-risk smokers for serum pepsinogen screening may be a cost-effective strategy to reduce intestinal-type NCGA mortality.

[Global health 2035: a world converging within a generation]. / Salud global 2035: un mundo convergiendo en el lapso de una generación.

Prompted by the 20th anniversary of the 1993 World Development Report, a Lancet Commission revisited the case for investment in health and developed a new investment framework to achieve dramatic health gains by 2035. The Commission's report has four key messages, each accompanied by opportunities for action by national governments of low-income and middle-income countries and by the international community. First, there is an enormous economic payoff from investing in health. The impressive returns make a strong case for both increased domestic financing of health and for allocating a higher proportion of official development assistance to development of health. Second, modeling by the Commission found that a "grand convergence" in health is achievable by 2035-that is, a reduction in infectious, maternal, and child mortality down to universally low levels. Convergence would require aggressive scale up of existing and new health tools, and it could mostly be financed from the expected economic growth of low- and middle-income countries. The international community can best support convergence by funding the development and delivery of new health technologies and by curbing antibiotic resistance. Third, fiscal policies -such as taxation of tobacco and alcohol- are a powerful and underused lever that governments can use to curb non-communicable diseases and injuries while also raising revenue for health. International action on NCDs and injuries should focus on providing technical assistance on fiscal policies, regional cooperation on tobacco, and funding policy and implementation research on scaling-up of interventions to tackle these conditions. Fourth, progressive universalism, a pathway to universal health coverage (UHC) that includes the poor from the outset, is an efficient way to achieve health and financial risk protection. For national governments, progressive universalism would yield high health gains per dollar spent and poor people would gain the most in terms of health and financial protection. The international community can best support countries to implement progressive UHC by financing policy and implementation research, such as on the mechanics of designing and implementing evolution of the benefits package as the resource envelope for public finance grows.

Global maternal mortality projections by urban/rural location and education level: a simulation-based analysis.

Background: Maternal mortality remains a challenge in global health, with well-known disparities across countries. However, less is known about disparities in maternal health by subgroups within countries. The aim of this study is to estimate maternal health indicators for subgroups of women within each country. Methods: In this simulation-based analysis, we used the empirically calibrated Global Maternal Health (GMatH) microsimulation model to estimate a range of maternal health indicators by subgroup (urban/rural location and level of education) for 200 countries/territories from 1990 to 2050. Education levels were defined as low (less than primary), middle (less than secondary), and high (completed secondary or higher). The model simulates the reproductive lifecycle of each woman, accounting for individual-level factors such as family planning preferences, biological factors (e.g., anemia), and history of maternal complications, and how these factors vary by subgroup. We also estimated the impact of scaling up women's education on projected maternal health outcomes compared to clinical and health system-focused interventions. Findings: We find large subgroup differences in maternal health outcomes, with an estimated global maternal mortality ratio (MMR) in 2022 of 292 (95% UI 250-341) for rural women and 100 (95% UI 84-116) for urban women, and 536 (95% UI 450-594), 143 (95% UI 117-174), and 85 (95% UI 67-108) for low, middle, and high education levels, respectively. Ensuring all women complete secondary school is associated with a large impact on the projected global MMR in 2030 (97 [95% UI 76-120]) compared to current trends (167 [95% UI 142-188]), with especially large improvements in countries such as Afghanistan, Chad, Madagascar, Niger, and Yemen. Interpretation: Substantial subgroup disparities present a challenge for global maternal health and health equity. Outcomes are especially poor for rural women with low education, highlighting the need to ensure that policy interventions adequately address barriers to care in rural areas, and the importance of investing in social determinants of health, such as women's education, in addition to health system interventions to improve maternal health for all women. Funding: John D. and Catherine T. MacArthur Foundation, 10-97002-000-INP.

Contribution of H. pylori and smoking trends to US incidence of intestinal-type noncardia gastric adenocarcinoma: a microsimulation model.

BACKGROUND: Although gastric cancer has declined dramatically in the US, the disease remains the second leading cause of cancer mortality worldwide. A better understanding of reasons for the decline can provide important insights into effective preventive strategies. We sought to estimate the contribution of risk factor trends on past and future intestinal-type noncardia gastric adenocarcinoma (NCGA) incidence. METHODS AND FINDINGS: We developed a population-based microsimulation model of intestinal-type NCGA and calibrated it to US epidemiologic data on precancerous lesions and cancer. The model explicitly incorporated the impact of Helicobacter pylori and smoking on disease natural history, for which birth cohort-specific trends were derived from the National Health and Nutrition Examination Survey (NHANES) and National Health Interview Survey (NHIS). Between 1978 and 2008, the model estimated that intestinal-type NCGA incidence declined 60% from 11.0 to 4.4 per 100,000 men, <3% discrepancy from national statistics. H. pylori and smoking trends combined accounted for 47% (range = 30%-58%) of the observed decline. With no tobacco control, incidence would have declined only 56%, suggesting that lower smoking initiation and higher cessation rates observed after the 1960s accelerated the relative decline in cancer incidence by 7% (range = 0%-21%). With continued risk factor trends, incidence is projected to decline an additional 47% between 2008 and 2040, the majority of which will be attributable to H. pylori and smoking (81%; range = 61%-100%). Limitations include assuming all other risk factors influenced gastric carcinogenesis as one factor and restricting the analysis to men. CONCLUSIONS: Trends in modifiable risk factors explain a significant proportion of the decline of intestinal-type NCGA incidence in the US, and are projected to continue. Although past tobacco control efforts have hastened the decline, full benefits will take decades to be realized, and further discouragement of smoking and reduction of H. pylori should be priorities for gastric cancer control efforts.

Simulation-based estimates and projections of global, regional and country-level maternal mortality by cause, 1990-2050.

Maternal mortality is a major global health challenge. Although progress has been made globally in reducing maternal deaths, measurement remains challenging given the many causes and frequent underreporting of maternal deaths. We developed the Global Maternal Health microsimulation model for women in 200 countries and territories, accounting for individual fertility preferences and clinical histories. Demographic, epidemiologic, clinical and health system data were synthesized from multiple sources, including the medical literature, Civil Registration Vital Statistics systems and Demographic and Health Survey data. We calibrated the model to empirical data from 1990 to 2015 and assessed the predictive accuracy of our model using indicators from 2016 to 2020. We projected maternal health indicators from 1990 to 2050 for each country and estimate that between 1990 and 2020 annual global maternal deaths declined by over 40% from 587,500 (95% uncertainty intervals (UI) 520,600-714,000) to 337,600 (95% UI 307,900-364,100), and are projected to decrease to 327,400 (95% UI 287,800-360,700) in 2030 and 320,200 (95% UI 267,100-374,600) in 2050. The global maternal mortality ratio is projected to decline to 167 (95% UI 142-188) in 2030, with 58 countries above 140, suggesting that on current trends, maternal mortality Sustainable Development Goal targets are unlikely to be met. Building on the development of our structural model, future research can identify context-specific policy interventions that could allow countries to accelerate reductions in maternal deaths.

A simulation-based comparative effectiveness analysis of policies to improve global maternal health outcomes.

The Sustainable Development Goals include a target to reduce the global maternal mortality ratio (MMR) to less than 70 maternal deaths per 100,000 live births by 2030, with no individual country exceeding 140. However, on current trends the goals are unlikely to be met. We used the empirically calibrated Global Maternal Health microsimulation model, which simulates individual women in 200 countries and territories to evaluate the impact of different interventions and strategies from 2022 to 2030. Although individual interventions yielded fairly small reductions in maternal mortality, integrated strategies were more effective. A strategy to simultaneously increase facility births, improve the availability of clinical services and quality of care at facilities, and improve linkages to care would yield a projected global MMR of 72 (95% uncertainty interval (UI) = 58-87) in 2030. A comprehensive strategy adding family planning and community-based interventions would have an even larger impact, with a projected MMR of 58 (95% UI = 46-70). Although integrated strategies consisting of multiple interventions will probably be needed to achieve substantial reductions in maternal mortality, the relative priority of different interventions varies by setting. Our regional and country-level estimates can help guide priority setting in specific contexts to accelerate improvements in maternal health.

Health and economic impact of HPV 16/18 vaccination and cervical cancer screening in Eastern Africa.

Eastern Africa has the world's highest cervical cancer incidence and mortality rates. We used epidemiologic data from Kenya, Mozambique, Tanzania, Uganda, and Zimbabwe to develop models of HPV-related infection and disease. For each country, we assessed HPV vaccination of girls before age 12 followed by screening with HPV DNA testing once, twice, or three times per lifetime (at ages 35, 40, 45). For women over age 30, we assessed only screening (with HPV DNA testing up to three times per lifetime or VIA at age 35). Assuming no waning immunity, mean reduction in lifetime cancer risk associated with vaccination ranged from 36 to 45%, and vaccination followed by screening once per lifetime at age 35 with HPV DNA testing ranged from 43 to 51%. For both younger and older women, the most effective screening strategy was HPV DNA testing three times per lifetime. Provided the cost per vaccinated girl was less than I$10 (I$2 per dose), vaccination had an incremental cost-effectiveness ratio [I$ (international dollars)/year of life saved (YLS)] less than the country-specific per capita GDP, a commonly cited heuristic for "very cost-effective" interventions. If the cost per vaccinated girl was between I$10 (I$2 per dose) and I$25 (I$5 per dose), vaccination followed by HPV DNA testing would save the most lives and would be considered good value for public health dollars. These results should be used to catalyze design and evaluation of HPV vaccine delivery and screening programs, and contribute to a dialogue on financing HPV vaccination in poor countries.

Patient- and population-level health consequences of discontinuing antiretroviral therapy in settings with inadequate HIV treatment availability.

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.

Assessing health and economic outcomes of interventions to reduce pregnancy-related mortality in Nigeria.

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).

Health and economic impact of human papillomavirus 16 and 18 vaccination of preadolescent girls and cervical cancer screening of adult women in Peru.

OBJECTIVE: To estimate the benefits, cost-effectiveness (i.e., value for money), and required financial costs (e.g., affordability) of adding human papillomavirus (HPV) vaccination to Peru's cervical cancer screening program. METHODS: Evidence (e.g., coverage, delivery costs) from an HPV vaccination demonstration project conducted in Peru was combined with epidemiological data in an empirically calibrated mathematical model to assess screening (HPV DNA testing three to five times per lifetime) and HPV vaccination under different cost, coverage, and efficacy assumptions. Model outcomes included lifetime risk of cancer reduction, cancer cases averted, lives saved, average life expectancy gains, short-term financial costs, and discounted long-term economic costs. RESULTS: Status quo low levels of screening (e.g., cytologic screening at 10.0% coverage) reduced lifetime risk of cervical cancer by 11.9%, compared to not screening. Adding vaccination of preadolescent girls at a coverage achieved in the demonstration program (82.0%) produced an additional 46.1% reduction, and would cost less than US$ 500 per year of life saved (YLS) at ~US$ 7/dose or ~US$ 1 300 at ~US$ 20/dose. One year of vaccination was estimated to cost ~US$ 5 million at ~US$ 5/dose or ~US$ 16 million at ~US$ 20/dose, including programmatic costs. Enhanced screening in adult women combined with preadolescent vaccination had incremental cost-effectiveness ratios lower than Peru's 2005 per capita gross domestic product (GDP; US$ 2 852, in 2009 US$), and would be considered cost-effective. CONCLUSIONS: Preadolescent HPV vaccination, followed by enhanced HPV DNA screening in adult women, could prevent two out of three cervical cancer deaths. Several strategies would be considered "good value" for resources invested, provided vaccine prices are low. While financial costs imply substantial immediate investments, the high-value payoff should motivate creative mechanisms for financing and scale-up of delivery programs.

Health and economic implications of HPV vaccination in the United States.

BACKGROUND: The cost-effectiveness of prophylactic vaccination against human papillomavirus types 16 (HPV-16) and 18 (HPV-18) is an important consideration for guidelines for immunization in the United States. METHODS: We synthesized epidemiologic and demographic data using models of HPV-16 and HPV-18 transmission and cervical carcinogenesis to compare the health and economic outcomes of vaccinating preadolescent girls (at 12 years of age) and vaccinating older girls and women in catch-up programs (to 18, 21, or 26 years of age). We examined the health benefits of averting other HPV-16-related and HPV-18-related cancers, the prevention of HPV-6-related and HPV-11-related genital warts and juvenile-onset recurrent respiratory papillomatosis by means of the quadrivalent vaccine, the duration of immunity, and future screening practices. RESULTS: On the assumption that the vaccine provided lifelong immunity, the cost-effectiveness ratio of vaccination of 12-year-old girls was $43,600 per quality-adjusted life-year (QALY) gained, as compared with the current screening practice. Under baseline assumptions, the cost-effectiveness ratio for extending a temporary catch-up program for girls to 18 years of age was $97,300 per QALY; the cost of extending vaccination of girls and women to the age of 21 years was $120,400 per QALY, and the cost for extension to the age of 26 years was $152,700 per QALY. The results were sensitive to the duration of vaccine-induced immunity; if immunity waned after 10 years, the cost of vaccination of preadolescent girls exceeded $140,000 per QALY, and catch-up strategies were less cost-effective than screening alone. The cost-effectiveness ratios for vaccination strategies were more favorable if the benefits of averting other health conditions were included or if screening was delayed and performed at less frequent intervals and with more sensitive tests; they were less favorable if vaccinated girls were preferentially screened more frequently in adulthood. CONCLUSIONS: The cost-effectiveness of HPV vaccination will depend on the duration of vaccine immunity and will be optimized by achieving high coverage in preadolescent girls, targeting initial catch-up efforts to women up to 18 or 21 years of age, and revising screening policies.

Effects of direct-to-consumer advertising and clinical guidelines on appropriate use of human papillomavirus DNA tests.

BACKGROUND: Both clinical guidelines and direct-to-consumer (DTC) advertising influence the use of new health care technologies, but little is known about their relative effects. The introduction of a cervical cancer screening test in 2000 offered a unique opportunity to assess the 2 strategies. OBJECTIVE: To evaluate the effects of clinical guidelines and a targeted DTC advertising campaign on overall and appropriate use of human papillomavirus (HPV) DNA tests. RESEARCH DESIGN: Quasi-experimental study using difference-in-differences analysis. Data were MarketScan private insurance claims for 500,000 women aged 21 to 64 enrolled at least 12 consecutive months from January 2001 through December 2005. RESULTS: Both clinical guidelines and DTC advertising were associated with increases in overall HPV DNA test use. DTC advertising was associated with a statistically significant increase in HPV DNA test use in 2 groups of DTC cities (+5.57%, P < 0.0001; +2.54%, P < 0.0001). DTC advertising was associated with comparable increases in the probability of appropriate and inappropriate use of the HPV DNA test in primary screening. Clinical guideline releases from the American College of Obstetricians and Gynecologists, and by a cosponsored panel, were associated with greater increases in HPV DNA tests for appropriate primary screening than for inappropriate primary screening (ß = 0.3347, P < 0.05 and ß = 0.4175, P < 0.01). CONCLUSIONS: DTC advertising was associated with increased overall use of a cervical cancer screening test, whereas clinical guidelines were differentially associated with increased appropriate use. These findings suggest distinct influences of consumer marketing and professional guidelines on the use of health care products and services.

Comparative evaluation of the potential impact of rotavirus versus HPV vaccination in GAVI-eligible countries: a preliminary analysis focused on the relative disease burden.

BACKGROUND: Immunization policymakers at global and local levels need to establish priorities among new vaccines competing for limited resources. However, comparison of the potential impact of single vaccination programs is challenging, primarily due to the limited number of vaccine analyses as well as their differing analytic approaches and reporting formats. The purpose of this study is to provide early insight into how the comparative impact of different new vaccines could be assessed in resource-poor settings with respect to affordability, cost-effectiveness, and distributional equity. METHODS: We compared the health, economic, and financial consequences of introducing the two vaccines in 72 GAVI-eligible countries using a number of different outcome measures to evaluate affordability, cost-effectiveness, and distributional equity. We use simple static models to standardize the analytic framework and improve comparability between the two new vaccines. These simple models were validated by leveraging previously developed, more complex models for rotavirus and human papillomavirus (HPV). RESULTS: With 70% coverage of a single-age cohort of infants and pre-adolescent girls, the lives saved with rotavirus (~274,000) and HPV vaccines (~286,000) are similar, although the timing of averted mortality differs; rotavirus-attributable deaths occur in close proximity to infection, while HPV-related cancer deaths occur largely after age 30. Deaths averted per 1000 vaccinated are 5.2 (rotavirus) and 12.6 (HPV). Disability-adjusted life years (DALYs) averted were ~7.15 million (rotavirus) and ~1.30 million (HPV), reflecting the greater influence of discounting on the latter, given the lagtime between vaccination and averted cancer. In most countries (68 for rotavirus and 66 for HPV, at the cost of I$25 per vaccinated individual) the incremental cost per DALY averted was lower than each country's GDP per capita. Financial resources required for vaccination with rotavirus are higher than with HPV since both genders are vaccinated. CONCLUSIONS: While lifesaving benefits of rotavirus and HPV vaccines will be realized at different times, the number of lives saved over each target populations' lifetimes will be similar. Model-based analyses that use a standardized analytic approach and generate comparable outputs can enrich the priority-setting dialogue. Although new vaccines may be deemed cost-effective, other factors including affordability and distributional equity need to be considered in different settings. We caution that for priority setting in an individual country, more rigorous comparisons should be performed, using more comprehensive models and considering all relevant vaccines and delivery strategies.

A model-based estimate of cumulative excess mortality in survivors of childhood cancer.

BACKGROUND: Although childhood cancer survival rates have dramatically increased, survivors face elevated risk for life-threatening late effects, including secondary cancer. OBJECTIVE: To estimate the cumulative effect of disease- and treatment-related mortality risks on survivor life expectancy. DESIGN: State-transition model to simulate the lifetime clinical course of childhood cancer survivors. SETTING: Childhood Cancer Survivor Study. PATIENTS: Five-year survivors of childhood cancer. MEASUREMENTS: Probabilities of risk for death from the original cancer diagnosis, excess mortality from subsequent cancer and cardiac, pulmonary, external, and other complications, and background mortality (age-specific mortality rates for the general population) were estimated over the lifetime of survivors of childhood cancer. RESULTS: For a cohort of 5-year survivors aged 15 years who received a diagnosis of cancer at age 10 years, the average lifetime probability was 0.10 for late-recurrence mortality; 0.15 for treatment-related subsequent cancer and death from cardiac, pulmonary, and external causes; and 0.05 for death from other excess risks. Life expectancy for the cohort of persons aged 15 years was 50.6 years, a loss of 10.4 years (17.1%) compared with the general population. Reduction in life expectancy varied by diagnosis, ranging from 4.0 years (6.0%) for kidney tumor survivors to more than 17.8 years (> or =28.0%) for brain and bone tumor survivors, and was sensitive to late-recurrence mortality risk and duration of excess mortality risk. LIMITATION: Estimates are based on data for survivors who received treatment 20 to 40 years ago; patients who received treatment more recently may have more favorable outcomes. CONCLUSION: Childhood cancer survivors face considerable mortality during adulthood, with excess risks reducing life expectancy by as much as 28%. Monitoring the health of current survivors and carefully evaluating therapies with known late toxicities in patients with newly diagnosed cancer are needed.

Cost-effectiveness analysis of cervical cancer prevention based on a rapid human papillomavirus screening test in a high-risk region of China.

This study assessed the cost-effectiveness of a new, rapid human papillomavirus (HPV)-DNA screening test for cervical cancer prevention in the high-risk region of Shanxi, China. Using micro-costing methods, we estimated the resources needed to implement preventive strategies using cervical cytology or HPV-DNA testing, including the Hybrid Capture 2 (hc2) test (QIAGEN Corp., Gaithersburg, MD) and the rapid HPV-DNA careHPV test (QIAGEN). Data were used in a previously published model and empirically calibrated to country-specific epidemiological data. Strategies differed by initial test, targeted age, frequency of screening, number of clinic visits required (1, 2 or 3) and service delivery setting (national, county and township levels). Outcomes included lifetime risk of cancer, years of life saved (YLS), lifetime costs and incremental cost-effectiveness ratios (cost per YLS). For all screening frequencies, the most efficient strategy used 2-visit rapid HPV-DNA testing at the county level, including screening and diagnostics in the first visit, and treatment in the second visit. Screening at ages 35, 40 and 45 reduced cancer risk by 50% among women compliant with all 3 screening rounds, and was US$ 150 per YLS, compared with this same strategy applied twice per lifetime. This would be considered very cost-effective evaluated against China's per-capita gross domestic product (US$ 1,702). By enhancing the linkage between screening and treatment through a reduced number of visits, rapid HPV-DNA testing 3 times per lifetime is more effective than traditional cytology, and is likely to be cost-effective in high-risk regions of China.

Alternative strategies to reduce maternal mortality in India: a cost-effectiveness analysis.

BACKGROUND: Approximately one-quarter of all pregnancy- and delivery-related maternal deaths worldwide occur in India. Taking into account the costs, feasibility, and operational complexity of alternative interventions, we estimate the clinical and population-level benefits associated with strategies to improve the safety of pregnancy and childbirth in India. METHODS AND FINDINGS: Country- and region-specific data were synthesized using a computer-based model that simulates the natural history of pregnancy (both planned and unintended) and pregnancy- and childbirth-associated complications in individual women; and considers delivery location, attendant, and facility level. Model outcomes included clinical events, population measures, costs, and cost-effectiveness ratios. Separate models were adapted to urban and rural India using survey-based data (e.g., unmet need for birth spacing/limiting, facility births, skilled birth attendants). Model validation compared projected maternal indicators with empiric data. Strategies consisted of improving coverage of effective interventions that could be provided individually or packaged as integrated services, could reduce the incidence of a complication or its case fatality rate, and could include improved logistics such as reliable transport to an appropriate referral facility as well as recognition of referral need and quality of care. Increasing family planning was the most effective individual intervention to reduce pregnancy-related mortality. If over the next 5 y the unmet need for spacing and limiting births was met, more than 150,000 maternal deaths would be prevented; more than US$1 billion saved; and at least one of every two abortion-related deaths averted. Still, reductions in maternal mortality reached a threshold ( approximately 23%-35%) without including strategies that ensured reliable access to intrapartum and emergency obstetrical care (EmOC). An integrated and stepwise approach was identified that would ultimately prevent four of five maternal deaths; this approach coupled stepwise improvements in family planning and safe abortion with consecutively implemented strategies that incrementally increased skilled attendants, improved antenatal/postpartum care, shifted births away from home, and improved recognition of referral need, transport, and availability/quality of EmOC. The strategies in this approach ranged from being cost-saving to having incremental cost-effectiveness ratios less than US$500 per year of life saved (YLS), well below India's per capita gross domestic product (GDP), a common benchmark for cost-effectiveness. CONCLUSIONS: Early intensive efforts to improve family planning and control of fertility choices and to provide safe abortion, accompanied by a paced systematic and stepwise effort to scale up capacity for integrated maternal health services over several years, is as cost-effective as childhood immunization or treatment of malaria, tuberculosis, or HIV. In just 5 y, more than 150,000 maternal deaths would be averted through increasing contraception rates to meet women's needs for spacing and limiting births; nearly US$1.5 billion would be saved by coupling safe abortion to aggressive family planning efforts; and with stepwise investments to improve access to pregnancy-related health services and to high-quality facility-based intrapartum care, more than 75% of maternal deaths could be prevented. If accomplished over the next decade, the lives of more than one million women would be saved.

Clinical benefits, costs, and cost-effectiveness of neonatal intensive care in Mexico.

BACKGROUND: Neonatal intensive care improves survival, but is associated with high costs and disability amongst survivors. Recent health reform in Mexico launched a new subsidized insurance program, necessitating informed choices on the different interventions that might be covered by the program, including neonatal intensive care. The purpose of this study was to estimate the clinical outcomes, costs, and cost-effectiveness of neonatal intensive care in Mexico. METHODS AND FINDINGS: A cost-effectiveness analysis was conducted using a decision analytic model of health and economic outcomes following preterm birth. Model parameters governing health outcomes were estimated from Mexican vital registration and hospital discharge databases, supplemented with meta-analyses and systematic reviews from the published literature. Costs were estimated on the basis of data provided by the Ministry of Health in Mexico and World Health Organization price lists, supplemented with published studies from other countries as needed. The model estimated changes in clinical outcomes, life expectancy, disability-free life expectancy, lifetime costs, disability-adjusted life years (DALYs), and incremental cost-effectiveness ratios (ICERs) for neonatal intensive care compared to no intensive care. Uncertainty around the results was characterized using one-way sensitivity analyses and a multivariate probabilistic sensitivity analysis. In the base-case analysis, neonatal intensive care for infants born at 24-26, 27-29, and 30-33 weeks gestational age prolonged life expectancy by 28, 43, and 34 years and averted 9, 15, and 12 DALYs, at incremental costs per infant of US$11,400, US$9,500, and US$3,000, respectively, compared to an alternative of no intensive care. The ICERs of neonatal intensive care at 24-26, 27-29, and 30-33 weeks were US$1,200, US$650, and US$240, per DALY averted, respectively. The findings were robust to variation in parameter values over wide ranges in sensitivity analyses. CONCLUSIONS: Incremental cost-effectiveness ratios for neonatal intensive care imply very high value for money on the basis of conventional benchmarks for cost-effectiveness analysis. Please see later in the article for the Editors' Summary.