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.

Comparative Effectiveness of Personalized Lifestyle Management Strategies for Cardiovascular Disease Risk Reduction.

BACKGROUND: Evidence shows that healthy diet, exercise, smoking interventions, and stress reduction reduce cardiovascular disease risk. We aimed to compare the effectiveness of these lifestyle interventions for individual risk profiles and determine their rank order in reducing 10-year cardiovascular disease risk. METHODS AND RESULTS: We computed risks using the American College of Cardiology/American Heart Association Pooled Cohort Equations for a variety of individual profiles. Using published literature on risk factor reductions through diverse lifestyle interventions-group therapy for stopping smoking, Mediterranean diet, aerobic exercise (walking), and yoga-we calculated the risk reduction through each of these interventions to determine the strategy associated with the maximum benefit for each profile. Sensitivity analyses were conducted to test the robustness of the results. In the base-case analysis, yoga was associated with the largest 10-year cardiovascular disease risk reductions (maximum absolute reduction 16.7% for the highest-risk individuals). Walking generally ranked second (max 11.4%), followed by Mediterranean diet (max 9.2%), and group therapy for smoking (max 1.6%). If the individual was a current smoker and successfully quit smoking (ie, achieved complete smoking cessation), then stopping smoking yielded the largest reduction. Probabilistic and 1-way sensitivity analysis confirmed the demonstrated trend. CONCLUSIONS: This study reports the comparative effectiveness of several forms of lifestyle modifications and found smoking cessation and yoga to be the most effective forms of cardiovascular disease prevention. Future research should focus on patient adherence to personalized therapies, cost-effectiveness of these strategies, and the potential for enhanced benefit when interventions are performed simultaneously rather than as single measures.

The effectiveness of yoga in modifying risk factors for cardiovascular disease and metabolic syndrome: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Yoga, a popular mind-body practice, may produce changes in cardiovascular disease (CVD) and metabolic syndrome risk factors. DESIGN: This was a systematic review and random-effects meta-analysis of randomized controlled trials (RCTs). METHODS: Electronic searches of MEDLINE, EMBASE, CINAHL, PsycINFO, and The Cochrane Central Register of Controlled Trials were performed for systematic reviews and RCTs through December 2013. Studies were included if they were English, peer-reviewed, focused on asana-based yoga in adults, and reported relevant outcomes. Two reviewers independently selected articles and assessed quality using Cochrane's Risk of Bias tool. RESULTS: Out of 1404 records, 37 RCTs were included in the systematic review and 32 in the meta-analysis. Compared to non-exercise controls, yoga showed significant improvement for body mass index (-0.77 kg/m(2) (95% confidence interval -1.09 to -0.44)), systolic blood pressure (-5.21 mmHg (-8.01 to -2.42)), low-density lipoprotein cholesterol (-12.14 mg/dl (-21.80 to -2.48)), and high-density lipoprotein cholesterol (3.20 mg/dl (1.86 to 4.54)). Significant changes were seen in body weight (-2.32 kg (-4.33 to -0.37)), diastolic blood pressure (-4.98 mmHg (-7.17 to -2.80)), total cholesterol (-18.48 mg/dl (-29.16 to -7.80)), triglycerides (-25.89 mg/dl (-36.19 to -15.60), and heart rate (-5.27 beats/min (-9.55 to -1.00)), but not fasting blood glucose (-5.91 mg/dl (-16.32 to 4.50)) nor glycosylated hemoglobin (-0.06% Hb (-0.24 to 0.11)). No significant difference was found between yoga and exercise. One study found an impact on smoking abstinence. CONCLUSIONS: There is promising evidence of yoga on improving cardio-metabolic health. Findings are limited by small trial sample sizes, heterogeneity, and moderate quality of RCTs.

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.

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

Con motivo del 20º aniversario del Informe sobre el Desarrollo Mundial 1993, una Comisión de la revista The Lancet reconsideró el argumento a favor de la inversión en salud y desarrolló un nuevo marco de inversión para lograr mejoras dramáticas en materia de salud para el año 2035. El informe de la Comisión contiene cuatro mensajes clave, cada uno acompañado de oportunidades para los gobiernos nacionales de países de ingresos bajos y medios y para la comunidad internacional. En primer lugar, invertir en salud acarrea enormes rendimientos económicos. Las impresionantes ganancias son un fuerte argumento a favor de un aumento en el financiamiento nacional de la salud y de asignar una mayor proporción de la asistencia oficial al desarrollo de la salud. En segundo lugar, en el modelo creado por la Comisión se encontró que es posible lograr para el año 2035 una "gran convergencia" en salud, consistente en la reducción de las tasas de mortalidad materna, infantil y por infecciones a niveles universalmente bajos. Tal convergencia requeriría la ampliación de las herramientas de salud existentes y un incremento agresivo de nuevas herramientas, y podría ser financiada en su mayor parte con recursos derivados del crecimiento económico esperado de los países de ingresos bajos y medios. La mejor manera en que la comunidad internacional puede apoyar la convergencia es financiando el desarrollo y suministro de nuevas tecnologías de salud, y frenando la resistencia a los antibióticos. En tercer lugar, las políticas fiscales -tales como los impuestos al tabaco y al alcohol- son una palanca poderosa y subutilizada que los gobiernos pueden emplear para detener el avance de las enfermedades no transmisibles (ENT) y las lesiones, a la vez que elevan los ingresos públicos para la salud. La acción internacional sobre las ENT y lesiones debería enfocarse en proporcionar asistencia técnica sobre políticas fiscales, en cooperación regional para el combate al tabaquismo y en financiar investigación sobre políticas e implementación para ampliar las intervenciones que enfrenten estos problemas. En cuarto lugar, la universalización progresiva -una vía hacia la cobertura universal de salud (CUS) que incluya desde el comienzo a los pobres- es una manera eficiente de lograr la protección a la salud contra riesgos financieros. Para los gobiernos nacionales, la universalización progresiva produciría elevadas ganancias en salud por cada dólar que se gaste en ésta, y los pobres serían quienes más ganarían en términos tanto de salud como de protección financiera. La mejor manera en que la comunidad internacional puede brindar apoyo a los países para implementar una CUS progresiva es financiando la investigación sobre políticas e implementación, por ejemplo, sobre la mecánica del diseño e instrumentación de la evolución del paquete de beneficios conforme crezca el presupuesto para las finanzas públicas.

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.

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.

The estimated mortality impact of vaccinations forecast to be administered during 2011-2020 in 73 countries supported by the GAVI Alliance.

INTRODUCTION: From August to December 2011, a multidisciplinary group with expertise in mathematical modeling was constituted by the GAVI Alliance and the Bill & Melinda Gates Foundation to estimate the impact of vaccination in 73 countries supported by the GAVI Alliance. METHODS: The number of deaths averted in persons projected to be vaccinated during 2011-2020 was estimated for ten antigens: hepatitis B, yellow fever, Haemophilus influenzae type B (Hib), Streptococcus pneumoniae, rotavirus, Neisseria meningitidis serogroup A, Japanese encephalitis, human papillomavirus, measles, and rubella. Impact was calculated as the difference in the number of deaths expected over the lifetime of vaccinated cohorts compared to the number of deaths expected in those cohorts with no vaccination. Numbers of persons vaccinated were based on 2011 GAVI Strategic Demand Forecasts with projected dates of vaccine introductions, vaccination coverage, and target population size in each country. RESULTS: By 2020, nearly all GAVI-supported countries with endemic disease are projected to have introduced hepatitis B, Hib, pneumococcal, rotavirus, rubella, yellow fever, N. meningitidis serogroup A, and Japanese encephalitis-containing vaccines; 55 (75 percent) countries are projected to have introduced human papillomavirus vaccine. Projected use of these vaccines during 2011-2020 is expected to avert an estimated 9.9 million deaths. Routine and supplementary immunization activities with measles vaccine are expected to avert an additional 13.4 million deaths. Estimated numbers of deaths averted per 1000 persons vaccinated were highest for first-dose measles (16.5), human papillomavirus (15.1), and hepatitis B (8.3) vaccination. Approximately 52 percent of the expected deaths averted will be in Africa, 27 percent in Southeast Asia, and 13 percent in the Eastern Mediterranean. CONCLUSION: Vaccination of persons during 2011-2020 in 73 GAVI-eligible countries is expected to have substantial public health impact, particularly in Africa and Southeast Asia, two regions with high mortality. The actual impact of vaccination in these countries may be higher than our estimates because several widely used antigens were not included in the analysis. The quality of our estimates is limited by lack of data on underlying disease burden and vaccine effectiveness against fatal disease outcomes in developing countries. We plan to update the estimates annually to reflect updated demand forecasts, to refine model assumptions based on results of new information, and to extend the analysis to include morbidity and economic benefits.

Health and economic impact of human papillomavirus 16 and 18 vaccination of preadolescent girls and cervical cancer screening of adult women in Peru / Repercusiones sanitarias y económicas de la vacunación de niñas preadolescentes contra los tipos 16 y 18 del virus del papiloma humano y el tamizaje del cáncer cervicouterino en las mujeres adultas en el Perú

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.

OBJETIVO: Calcular los beneficios, la rentabilidad (relación costo-efectividad), y los costos financieros (asequibilidad) de añadir la vacunación contra el virus del papiloma humano (VPH) al programa de tamizaje del cáncer cervicouterino en el Perú. MÉTODOS: Se combinaron los datos probatorios (por ejemplo, cobertura, costos de prestación) de un proyecto piloto de vacunación contra el VPH llevado a cabo en el Perú con datos epidemiológicos, en un modelo matemático calibrado empíricamente para evaluar el tamizaje (prueba de ADN del VPH tres a cinco veces durante toda la vida) y la vacunación contra el VPH, según diferentes supuestos de costo, cobertura y eficacia. Los resultados del modelo incluían la reducción del riesgo de cáncer durante toda la vida, los casos de cáncer evitados, las vidas salvadas, los incrementos de la esperanza media de vida, los costos financieros a corto plazo y los costos económicos a largo plazo actualizados. RESULTADOS: Los bajos niveles de tamizaje actuales (cobertura del tamizaje citológico de 10,0 %) redujeron en 11,9 % el riesgo de cáncer cervicouterino durante toda la vida en comparación con la ausencia de tamizaje. La adición de la vacunación de las niñas preadolescentes con la cobertura alcanzada en el programa piloto (82,0 %) produjo una reducción adicional de 46,1 % y costaría menos de US$ 500 por cada año de vida salvado a US$ 7 la dosis, o de US$ 1 300 a US$ 20 la dosis. Se calculó que el costo de las vacunaciones de un año era aproximadamente de US$ 5 millones a unos US$ 5 la dosis o de aproximadamente US$ 16 millones a unos US$ 20 la dosis, incluidos los costos programáticos. La mejora del tamizaje en las mujeres adultas combinada con la vacunación de las preadolescentes mostraba cocientes de rentabilidad incremental inferiores al producto interno bruto per cápita del Perú en el año 2005 (PIB US$ 2 852, en dólares del 2009), y se consideraría rentable. CONCLUSIONES: La vacunación de las preadolescentes contra el VPH, junto con la mejora del tamizaje mediante la prueba de ADN del VPH en las mujeres adultas, podría prevenir dos de cada tres muertes debidas a cáncer cervicouterino. Varias estrategias se considerarían rentables en relación con los recursos invertidos, a condición de que el precio de la vacuna sea bajo. Aunque los costos financieros implican inversiones inmediatas sustanciales, el valor elevado de los beneficios debe motivar la elaboración de mecanismos creativos para financiar y extender los programas de prestación de servicios.

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.

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.

Model-based analyses to compare health and economic outcomes of cancer control: inclusion of disparities.

BACKGROUND: Disease simulation models of the health and economic consequences of different prevention and treatment strategies can guide policy decisions about cancer control. However, models that also consider health disparities can identify strategies that improve both population health and its equitable distribution. METHODS: We devised a typology of cancer disparities that considers types of inequalities among black, white, and Hispanic populations across different cancers and characteristics important for near-term policy discussions. We illustrated the typology in the specific example of cervical cancer using an existing disease simulation model calibrated to clinical, epidemiological, and cost data for the United States. We calculated average reduction in cancer incidence overall and for black, white, and Hispanic women under five different prevention strategies (Strategies A1, A2, A3, B, and C) and estimated average costs and life expectancy per woman, and the cost-effectiveness ratio for each strategy. RESULTS: Strategies that may provide greater aggregate health benefit than existing options may also exacerbate disparities. Combining human papillomavirus vaccination (Strategy A2) with current cervical cancer screening patterns (Strategy A1) resulted in an average reduction of 69% in cancer incidence overall but a 71.6% reduction for white women, 68.3% for black women, and 63.9% for Hispanic women. Other strategies targeting risk-based screening to racial and ethnic minorities reduced disparities among racial subgroups and resulted in more equitable distribution of benefits among subgroups (reduction in cervical cancer incidence, white vs. Hispanic women, 69.7% vs. 70.1%). Strategies that employ targeted risk-based screening and new screening algorithms, with or without vaccination (Strategies B and C), provide excellent value. The most effective strategy (Strategy C) had a cost-effectiveness ratio of $28,200 per year of life saved when compared with the same strategy without vaccination. CONCLUSIONS: We identify screening strategies for cervical cancer that provide greater aggregate health benefit than existing options, offer excellent cost-effectiveness, and have the biggest positive impact in worst-off groups. The typology proposed here may also be useful in research and policy decisions when trade-offs between fairness and cost-effectiveness are unavoidable.

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.

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.

Assessing the performance of a computer-based policy model of HIV and AIDS.

BACKGROUND: Model-based analyses, conducted within a decision analytic framework, provide a systematic way to combine information about the natural history of disease and effectiveness of clinical management strategies with demographic and epidemiological characteristics of the population. Among the challenges with disease-specific modeling include the need to identify influential assumptions and to assess the face validity and internal consistency of the model. METHODS AND FINDINGS: We describe a series of exercises involved in adapting a computer-based simulation model of HIV disease to the Women's Interagency HIV Study (WIHS) cohort and assess model performance as we re-parameterized the model to address policy questions in the U.S. relevant to HIV-infected women using data from the WIHS. Empiric calibration targets included 24-month survival curves stratified by treatment status and CD4 cell count. The most influential assumptions in untreated women included chronic HIV-associated mortality following an opportunistic infection, and in treated women, the 'clinical effectiveness' of HAART and the ability of HAART to prevent HIV complications independent of virologic suppression. Good-fitting parameter sets required reductions in the clinical effectiveness of 1st and 2nd line HAART and improvements in 3rd and 4th line regimens. Projected rates of treatment regimen switching using the calibrated cohort-specific model closely approximated independent analyses published using data from the WIHS. CONCLUSIONS: The model demonstrated good internal consistency and face validity, and supported cohort heterogeneities that have been reported in the literature. Iterative assessment of model performance can provide information about the relative influence of uncertain assumptions and provide insight into heterogeneities within and between cohorts. Description of calibration exercises can enhance the transparency of disease-specific models.

Cost-effectiveness of human papillomavirus vaccination and screening in Spain.

BACKGROUND: In Spain, prophylactic vaccination against human papillomavirus (HPV) types 16 and 18 is being offered free-of-charge to one birth cohort of girls aged 11-14. Screening is opportunistic (annual/biannual) contributing to social and geographical disparities. METHODS: A multi-HPV-type microsimulation model was calibrated to epidemiologic data from Spain utilising likelihood-based methods to assess the health and economic impact of adding HPV vaccination to cervical cancer screening. Strategies included (1) screening alone of women over age 25, varying frequency (every 1-5 years) and test (cytology, HPV DNA testing); (2) HPV vaccination of 11-year-old girls combined with screening. Outcomes included lifetime cancer risk, life expectancy, lifetime costs, number of clinical procedures and incremental cost-effectiveness ratios. RESULTS: After the introduction of HPV vaccination, screening will need to continue, and strategies that incorporated HPV testing are more effective and cost-effective than those with cytology alone. For vaccinated girls, 5-year organised cytology with HPV testing as triage from ages 30 to 65 costs 24,350€ per year of life saved (YLS), assuming life-long vaccine immunity against HPV-16/18 by 3 doses with 90% coverage. Unvaccinated girls would benefit from organised cytology screening with HPV testing as triage; 5-year screening from ages 30 to 65 costs 16,060€/YLS and 4-year screening from ages 30 to 85 costs 38,250€/YLS. Interventions would be cost-effective depending on the cost-effectiveness threshold and the vaccine price. CONCLUSIONS: In Spain, inequitable coverage and overuse of cytology make screening programmes inefficient. If high vaccination coverage among pre-adolescent girls is achieved, organised cytology screening with HPV triage starting at ages 30 to at least 65 every 4-5 years represents the best balance between costs and benefits.

Cost-effectiveness of treatment and endoscopic surveillance of precancerous lesions to prevent gastric cancer.

BACKGROUND: Although surveillance for Barrett esophagus and other gastrointestinal precancerous conditions is recommended, no analogous guidelines exist for gastric lesions. The objective of this study was to estimate the clinical benefits and cost-effectiveness of treatment and endoscopic surveillance to prevent gastric cancer. METHODS: The authors developed a state-transition decision model for a cohort of US men with a recent incidental diagnosis of gastric precancerous lesions (dysplasia, intestinal metaplasia, or atrophy). Strategies included 1) no surveillance or treatment and 2) referral for surveillance and treatment, and varied by surveillance frequency (none, every 10 years, every 5 years, or every year) and treatment modality for dysplastic and cancerous lesions (surgery or endoscopic mucosal resection [EMR]). The term "post-treatment surveillance" was restricted to surveillance of individuals after treatment. Data were based on published literature and databases. Outcomes included lifetime gastric cancer risk, quality-adjusted life expectancy, lifetime costs, and incremental cost-effectiveness ratios. RESULTS: For a cohort of men with dysplasia aged 50 years, the lifetime gastric cancer risk was 5.9%. EMR with annual surveillance reduced the lifetime cancer risk by 90% and cost $39,800 per quality-adjusted life year (QALY). Addition of post-treatment surveillance every 10 years provided little incremental benefit ( approximately 5%) but cost >$1 million per QALY. Results were most sensitive to surgical risks and the proportion of lesions completely removed with EMR. For intestinal metaplasia, surveillance every 10 years reduced lifetime cancer risk by 61% and cost $544,500 per QALY. CONCLUSIONS: EMR with surveillance every 1 to 5 years for gastric dysplasia was promising for secondary cancer prevention and had a cost-effectiveness ratio that would be considered attractive in the United States. Endoscopic surveillance of less advanced lesions did not appear to be cost-effective, except possibly for immigrants from high-risk countries.

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.

Empirically evaluating decision-analytic models.

OBJECTIVES: Model-based cost-effectiveness analyses support decision-making. To augment model credibility, evaluation via comparison to independent, empirical studies is recommended. METHODS: We developed a structured reporting format for model evaluation and conducted a structured literature review to characterize current model evaluation recommendations and practices. As an illustration, we applied the reporting format to evaluate a microsimulation of human papillomavirus and cervical cancer. The model's outputs and uncertainty ranges were compared with multiple outcomes from a study of long-term progression from high-grade precancer (cervical intraepithelial neoplasia [CIN]) to cancer. Outcomes included 5 to 30-year cumulative cancer risk among women with and without appropriate CIN treatment. Consistency was measured by model ranges overlapping study confidence intervals. RESULTS: The structured reporting format included: matching baseline characteristics and follow-up, reporting model and study uncertainty, and stating metrics of consistency for model and study results. Structured searches yielded 2963 articles with 67 meeting inclusion criteria and found variation in how current model evaluations are reported. Evaluation of the cervical cancer microsimulation, reported using the proposed format, showed a modeled cumulative risk of invasive cancer for inadequately treated women of 39.6% (30.9-49.7) at 30 years, compared with the study: 37.5% (28.4-48.3). For appropriately treated women, modeled risks were 1.0% (0.7-1.3) at 30 years, study: 1.5% (0.4-3.3). CONCLUSIONS: To support external and projective validity, cost-effectiveness models should be iteratively evaluated as new studies become available, with reporting standardized to facilitate assessment. Such evaluations are particularly relevant for models used to conduct comparative effectiveness analyses.