Estimating the Cost of Cervical Cancer Screening in Five Developing Countries

Background: Cost-effectiveness analyses (CEAs) can provide useful information to policymakers concerned with the broad allocation of resources as well as to local decision makers choosing between different options for reducing the burden from a single disease. For the latter, it is important to use country-specific data when possible and to represent cost differences between countries that might make one strategy more or less attractive than another strategy locally. As part of a CEA of cervical cancer screening in five developing countries, we supplemented limited primary cost data by developing other estimation techniques for direct medical and non-medical costs associated with alternative screening approaches using one of three initial screening tests: simple visual screening, HPV DNA testing, and cervical cytology. Here, we report estimation methods and results for three cost areas in which data were lacking. Methods: To supplement direct medical costs, including staff, supplies, and equipment depreciation using country-specific data, we used alternative techniques to quantify cervical cytology and HPV DNA laboratory sample processing costs. We used a detailed quantity and price approach whose face validity was compared to an adaptation of a US laboratory estimation methodology. This methodology was also used to project annual sample processing capacities for each laboratory type. The cost of sample transport from the clinic to the laboratory was estimated using spatial models. A plausible range of the cost of patient time spent seeking and receiving screening was estimated using only formal sector employment and wages as well as using both formal and informal sector participation and country-specific minimum wages. Data sources included primary data from country-specific studies, international databases, international prices, and expert opinion. Costs were standardized to year 2000 international dollars using inflation adjustment and purchasing power parity. Results: Cervical cytology laboratory processing costs were I$1.57–3.37 using the quantity and price method compared to I$1.58–3.02 from the face validation method. HPV DNA processing costs were I$6.07–6.59. Rural laboratory transport costs for cytology were I$0.12–0.64 and I$0.14–0.74 for HPV DNA laboratories. Under assumptions of lower resource efficiency, these estimates increased to I$0.42–0.83 and I$0.54–1.06. Estimates of the value of an hour of patient time using only formal sector participation were I$0.07–4.16, increasing to I$0.30–4.80 when informal and unpaid labor was also included. The value of patient time for traveling, waiting, and attending a screening visit was I$0.68–17.74. With the total cost of screening for cytology and HPV DNA testing ranging from I$4.85–40.54 and I$11.30–48.77 respectively, the cost of the laboratory transport, processing, and patient time accounted for 26–66% and 33–65% of the total costs. From a payer perspective, laboratory transport and processing accounted for 18–48% and 25–60% of total direct medical costs of I$4.11–19.96 and I$10.57–28.18 respectively. Conclusion: Cost estimates of laboratory processing, sample transport, and patient time account for a significant proportion of total cervical cancer screening costs in five developing countries and provide important inputs for CEAs of alternative screening modalities

Cost effectiveness analysis of including boys in a human papillomavirus vaccination programme in the United States

Objective To assess the cost effectiveness of including preadolescent boys in a routine human papillomavirus (HPV) vaccination programme for preadolescent girls

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)

Cost-effectiveness of Rotavirus vaccination in Vietnam

Background: Rotavirus is the most common cause of severe diarrhea leading to hospitalization or disease-specific death among young children. New rotavirus vaccines have recently been approved. Some previous studies have provided broad qualitative insights into the health and economic consequences of introducing the vaccines into low-income countries, representing several features of rotavirus infection, such as varying degrees of severity and age-dependency of clinical manifestation, in their model-based analyses. We extend this work to reflect additional features of rotavirus (e.g., the possibility of reinfection and varying degrees of partial immunity conferred by natural infection), and assess the influence of the features on the cost-effectiveness of rotavirus vaccination. Methods: We developed a Markov model that reflects key features of rotavirus infection, using the most recent data available. We applied the model to the 2004 Vietnamese birth cohort and reevaluated the cost-effectiveness (2004 US dollars per disability-adjusted life year [DALY]) of rotavirus vaccination (Rotarix®) compared to no vaccination, from both societal and health care system perspectives. We conducted univariate sensitivity analyses and also performed a probabilistic sensitivity analysis, based on Monte Carlo simulations drawing parameter values from the distributions assigned to key uncertain parameters. Results: Rotavirus vaccination would not completely protect young children against rotavirus infection due to the partial nature of vaccine immunity, but would effectively reduce severe cases of rotavirus gastroenteritis (outpatient visits, hospitalizations, or deaths) by about 67% over the first 5 years of life. Under base-case assumptions (94% coverage and $5 per dose), the incremental cost per DALY averted from vaccination compared to no vaccination would be$540 from the societal perspective and $550 from the health care system perspective. Conclusion: Introducing rotavirus vaccines would be a cost-effective public health intervention in Vietnam. However, given the uncertainty about vaccine efficacy and potential changes in rotavirus epidemiology in local settings, further clinical research and re-evaluation of rotavirus vaccination programs may be necessary as new information emerges

Cost-Effectiveness of Alternative Blood-Screening Strategies for West Nile Virus in the United States

BACKGROUND: West Nile virus (WNV) is endemic in the US, varying seasonally and by geographic region. WNV can be transmitted by blood transfusion, and mandatory screening of blood for WNV was recently introduced throughout the US. Guidelines for selecting cost-effective strategies for screening blood for WNV do not exist. METHODS AND FINDINGS: We conducted a cost-effectiveness analysis for screening blood for WNV using a computer-based mathematical model, and using data from prospective studies, retrospective studies, and published literature. For three geographic areas with varying WNV-transmission intensity and length of transmission season, the model was used to estimate lifetime costs, quality-adjusted life expectancy, and incremental cost-effectiveness ratios associated with alternative screening strategies in a target population of blood-transfusion recipients. We compared the status quo (baseline screening using a donor questionnaire) to several strategies which differed by nucleic acid testing of either pooled or individual samples, universal versus targeted screening of donations designated for immunocompromised patients, and seasonal versus year-long screening. In low-transmission areas with short WNV seasons, screening by questionnaire alone was the most cost-effective strategy. In areas with high levels of WNV transmission, seasonal screening of individual samples and restricting screening to blood donations designated for immunocompromised recipients was the most cost-effective strategy. Seasonal screening of the entire recipient pool added minimal clinical benefit, with incremental cost-effectiveness ratios exceeding US$1.7 million per quality-adjusted life-year gained. Year-round screening offered no additional benefit compared to seasonal screening in any of the transmission settings. CONCLUSIONS: In areas with high levels of WNV transmission, seasonal screening of individual samples and restricting screening to blood donations designated for immunocompromised recipients is cost saving. In areas with low levels of infection, a status-quo strategy using a standard questionnaire is cost-effective

The Cost-Effectiveness of Directly Observed Highly-Active Antiretroviral Therapy in the Third Trimester in HIV-Infected Pregnant Women

Background: In HIV-infected pregnant women, viral suppression prevents mother-to-child HIV transmission. Directly observed highly-active antiretroviral therapy (HAART) enhances virological suppression, and could prevent transmission. Our objective was to project the effectiveness and cost-effectiveness of directly observed administration of antiretroviral drugs in pregnancy. Methods and Findings: A mathematical model was created to simulate cohorts of one million asymptomatic HIV-infected pregnant women on HAART, with women randomly assigned self-administered or directly observed antiretroviral therapy (DOT), or no HAART, in a series of Monte Carlo simulations. Our primary outcome was the quality-adjusted life expectancy in years (QALY) of infants born to HIV-infected women, with the rates of Caesarean section and HIV-transmission after DOT use as intermediate outcomes. Both self-administered HAART and DOT were associated with decreased costs and increased life-expectancy relative to no HAART. The use of DOT was associated with a relative risk of HIV transmission of 0.39 relative to conventional HAART; was highly cost-effective in the cohort as a whole (cost-utility ratio $14,233 per QALY); and was cost-saving in women whose viral loads on self-administered HAART would have exceeded 1000 copies/ml. Results were stable in wide-ranging sensitivity analyses, with directly observed therapy cost-saving or highly cost-effective in almost all cases. Conclusions: Based on the best available data, programs that optimize adherence to HAART through direct observation in pregnancy have the potential to diminish mother-to-child HIV transmission in a highly cost-effective manner. Targeted use of DOT in pregnant women with high viral loads, who could otherwise receive self-administered HAART would be a cost-saving intervention. These projections should be tested with randomized clinical trials

Potential impact of reactive vaccination in controlling cholera outbreaks: An exploratory analysis using a Zimbabwean experience

Background. To contain ongoing cholera outbreaks, the World Health Organization has suggested that reactive vaccination should be considered in addition to its previous control measures. Objectives. To explore the potential impact of a hypothetical reactive oral cholera vaccination using the example of the recent large-scale cholera outbreak in Zimbabwe. Methods. This was a retrospective cost-effectiveness analysis calculating the health and economic burden of the cholera outbreak in Zimbabwe with and without reactive vaccination. The primary outcome measure was incremental cost per disability-adjusted life year (DALY) averted. Results. Under the base-case assumptions (assuming 50% coverage among individuals aged ≥2 years), reactive vaccination could have averted 1 320 deaths and 23 650 DALYs. Considering herd immunity, the corresponding values would have been 2 920 deaths and 52 360 DALYs averted. The total vaccination costs would have been ~$74 million and ~$21 million, respectively, with per-dose vaccine price of US$5 and$1. The incremental costs per DALY averted of reactive vaccination were $2 770 and$370, respectively, for vaccine price set at $5 and$1. Assuming herd immunity, the corresponding cost was $980 with vaccine price of$5, and the programme was cost-saving with a vaccine price of $1. Results were most sensitive to case-fatality rate, per-dose vaccine price, and the size of the outbreak. Conclusions. Reactive vaccination has the potential to be a cost-effective measure to contain cholera outbreaks in countries at high risk. However, the feasibility of implementation should be further evaluated, and caution is warranted in extrapolating the findings to different settings in the absence of other in-depth studies

Clinical consequences and cost of limiting use of vancomycin for perioperative prophylaxis: Example of coronary artery bypass surgery. Emerg Infect Dis

Routine use of vancomycin for perioperative prophylaxis is discouraged, principally to minimize microbial resistance to it. However, outcomes and costs of this recommendation have not been assessed. We used decisionanalytic models to compare clinical results and cost-effectiveness of no prophylaxis, cefazolin, and vancomycin, in coronary artery bypass graft surgery. In the base case, vancomycin resulted in 7% fewer surgical site infections and 1% lower all-cause mortality and saved $117 per procedure, compared with cefazolin. Cefazolin, in turn, resulted in substantially fewer infections and deaths and lower costs than no prophylaxis. We conclude that perioperative antibiotic prophylaxis with vancomycin is usually more effective and less expensive than cefazolin. Data on vancomycin's impact on resistance are needed to quantify the trade-off between individual patients' improved clinical outcomes and lower costs and the future longterm consequences to society. The emergence of vancomycin-resistant enterococci has opened a new era of hardly treatable bacterial infections, and there is now evidence that more virulent common pathogens such as Staphylococcus aureus can also develop resistance to vancomycin (1,2). The use of vancomycin is hypothesized to promote the development or transmission of this resistance (3,4). Restrictive guidelines have therefore been disseminated for the use of vancomycin or teicoplanin, another glycopeptide agent (5). These guidelines include a recommendation against the routine use of vancomycin as perioperative antibiotic prophylaxis for surgical site infections. However, vancomycin is preferred for preventing infections caused by methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-resistant coagulase-negative staphylococci. This is the rationale for recommending vancomycin prophylaxis when the risk for infection from methicillinresistant pathogens is high (6-11), although no guideline has made a clear statement on when to use this alternative. Since antibiotics are commonly used for prophylaxis, liberal interpretation of the prophylaxis guidelines will clearly jeopardize efforts to limit the use of vancomycin. Vancomycin is also more expensive to purchase and administer than cephalosporins. To inform both the clinical and public policy debate with respect to the optimal prophylaxis regimen, we conducted a cost-effectiveness analysis to compare the short-and longterm consequences of using vancomycin and cefazolin as first-line perioperative prophylaxis. We focused on patients who underwent coronary artery bypass graft surgery (CABG) because this is a large, relatively homogeneous population with substantial risk for serious surgical site infection (12,13). Methods Cost-Effectiveness Analysis We developed a decision-analytic model We also conducted a reference case analysis, as recommended by the Panel on Cost-Effectiveness in Health and Medicine (14), which assumed a societal perspective and relied on a longer time horizon. The reference case was a 65-year-old man undergoing CABG surgery for stable multivessel coronary heart disease. A state-transition model incorporated the lifetime probability of death, myocardial infarction, angina, or asymptomatic coronary artery disease following CABG surgery (15,16) to estimate life expectancy, qualityadjusted life expectancy, and total lifetime costs. Future costs and benefits were discounted at an annual rate of 3%

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

Modeling human papillomavirus and cervical cancer in the United States for analyses of screening and vaccination

Background: To provide quantitative insight into current U.S. policy choices for cervical cancer prevention, we developed a model of human papillomavirus (HPV) and cervical cancer, explicitly incorporating uncertainty about the natural history of disease. Methods: We developed a stochastic microsimulation of cervical cancer that distinguishes different HPV types by their incidence, clearance, persistence, and progression. Input parameter sets were sampled randomly from uniform distributions, and simulations undertaken with each set. Through systematic reviews and formal data synthesis, we established multiple epidemiologic targets for model calibration, including age-specific prevalence of HPV by type, age-specific prevalence of cervical intraepithelial neoplasia (CIN), HPV type distribution within CIN and cancer, and age-specific cancer incidence. For each set of sampled input parameters, likelihood-based goodness-of-fit (GOF) scores were computed based on comparisons between model-predicted outcomes and calibration targets. Using 50 randomly resampled, good-fitting parameter sets, we assessed the external consistency and face validity of the model, comparing predicted screening outcomes to independent data. To illustrate the advantage of this approach in reflecting parameter uncertainty, we used the 50 sets to project the distribution of health outcomes in U.S. women under different cervical cancer prevention strategies. Results: Approximately 200 good-fitting parameter sets were identified from 1,000,000 simulated sets. Modeled screening outcomes were externally consistent with results from multiple independent data sources. Based on 50 good-fitting parameter sets, the expected reductions in lifetime risk of cancer with annual or biennial screening were 76% (range across 50 sets: 69–82%) and 69% (60–77%), respectively. The reduction from vaccination alone was 75%, although it ranged from 60% to 88%, reflecting considerable parameter uncertainty about the natural history of type-specific HPV infection. The uncertainty surrounding the model-predicted reduction in cervical cancer incidence narrowed substantially when vaccination was combined with every-5-year screening, with a mean reduction of 89% and range of 83% to 95%. Conclusion: We demonstrate an approach to parameterization, calibration and performance evaluation for a U.S. cervical cancer microsimulation model intended to provide qualitative and quantitative inputs into decisions that must be taken before long-term data on vaccination outcomes become available. This approach allows for a rigorous and comprehensive description of policy-relevant uncertainty about health outcomes under alternative cancer prevention strategies. The model provides a tool that can accommodate new information, and can be modified as needed, to iteratively assess the expected benefits, costs, and cost-effectiveness of different policies in the U.S