Cost-effectiveness of HBV and HCV screening strategies:a systematic review of existing modelling techniques

Introduction: Studies evaluating the cost-effectiveness of screening for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are generally heterogeneous in terms of risk groups, settings, screening intervention, outcomes and the economic modelling framework. It is therefore difficult to compare cost-effectiveness results between studies. This systematic review aims to summarise and critically assess existing economic models for HBV and HCV in order to identify the main methodological differences in modelling approaches. Methods: A structured search strategy was developed and a systematic review carried out. A critical assessment of the decision-analytic models was carried out according to the guidelines and framework developed for assessment of decision-analytic models in Health Technology Assessment of health care interventions. Results: The overall approach to analysing the cost-effectiveness of screening strategies was found to be broadly consistent for HBV and HCV. However, modelling parameters and related structure differed between models, producing different results. More recent publications performed better against a performance matrix, evaluating model components and methodology. Conclusion: When assessing screening strategies for HBV and HCV infection, the focus should be on more recent studies, which applied the latest treatment regimes, test methods and had better and more complete data on which to base their models. In addition to parameter selection and associated assumptions, careful consideration of dynamic versus static modelling is recommended. Future research may want to focus on these methodological issues. In addition, the ability to evaluate screening strategies for multiple infectious diseases, (HCV and HIV at the same time) might prove important for decision makers

The economics of infectious diseases

Economics can make immensely valuable contributions to our understanding of infectious disease transmission and the design of effective policy responses. The one unique characteristic of infectious diseases makes it also particularly complicated to analyze: the fact that it is transmitted from person to person. It explains why individuals’ behavior and externalities are a central topic for the economics of infectious diseases. Many public health interventions are built on the assumption that individuals are altruistic and consider the benefits and costs of their actions to others. This would imply that even infected individuals demand prevention, which stands in conflict with the economic theory of rational behavior. Empirical evidence is conflicting for infected individuals. For healthy individuals, evidence suggests that the demand for prevention is affected by real or perceived risk of infection. However, studies are plagued by underreporting of preventive behavior and non-random selection into testing. Some empirical studies have shown that the impact of prevention interventions could be far greater than one case prevented, resulting in significant externalities. Therefore, economic evaluations need to build on dynamic transmission models in order to correctly estimate these externalities. Future research needs are significant. Economic research needs to improve our understanding of the role of human behavior in disease transmission; support the better integration of economic and epidemiological modeling, evaluation of large-scale public health interventions with quasi-experimental methods, design of optimal subsidies for tackling the global threat of antimicrobial resistance, refocusing the research agenda toward underresearched diseases; and most importantly to assure that progress translates into saved lives on the ground by advising on effective health system strengthening

A mathematical investigation of the effects of sexual orientation and HIV status on HPV transmission and vaccination

The effect of the inclusion of sexual behaviour, particularly three sexual orientation classes, on the transmission dynamics of HPV and cervical cancer incidence was investigated. A comprehensive literature review of mathematical models of HPV transmission and the natural history of cervical cancer was concluded. A mathematical model using ordinary differential equations was developed, which incorporated the three sexual orientation classes, and a sexual mixing algorithm for modelling the transmission dynamics. Reproduction numbers, determined through a simplified version of the developed model, indicated that the bisexual population could form a bridge between the heterosexual and homosexual population. The level of interaction is determined by the selection preferences of a bisexual individual to form a partnership with an individual of the same or opposite sex. The model was simulated, with parameters based on a South African population and HPV type 16/18, to investigate the effects of HIV status, sexual orientation and various vaccination strategies on HPV transmission and cervical cancer incidence. The results indicated that HIV status is a significant factor when determining cervical cancer incidence. The results regarding vaccination strategies agreed with results from the literature review with a two sex before sexual debut and catch up program the most effective, noting that with increased vaccination coverage of females the marginal impact on cervical cancer incidence of this approach diminished

Implementing partially effective HIV prevention programs: changes in sexual risk behavior and epidemic impact in Sub-Saharan Africa

While there is no magic bullet that can completely prevent HIV transmission and halt the HIV/AIDS pandemic, governments and policy makers have an array of partially-effective HIV prevention programs from which to choose, including the use of existing interventions (e.g. education and condom use) and technologies under development (e.g. microbicides and vaccines). Complex decisions regarding if, when, and how to implement various programs with partial efficacy must be made, often in the absence of data on program outcomes. Additionally, the quantitative tradeoff between program-related decreases in HIV transmission and the effects of risk behavior change is often unknown. The potential for changes in risk behavior to influence outcomes at the individual and population levels raises significant operational and ethical concerns regarding the magnitude of program benefits.Epidemiological data collection of sexual risk-taking behavior and mathematical modeling of population HIV transmission dynamics are used here in a multidisciplinary approach to examine the implications of risk behavior change surrounding the implementation of HIV prevention programs with less than 100% efficacy. This topic is explored within a South African context---specifically, the urban township of Soweto, which has a generalized, predominantly heterosexual HIV epidemic representative of populations throughout sub-Saharan Africa.The subject of risk behavior change associated with prevention program implementation arises most frequently in discussions regarding HIV vaccine development and use. The first and second papers contain analyses of self-reported data on current and anticipated sexual risk-taking behavior from adults undergoing screening and enrollment into HIV vaccine trials. The third paper describes a mathematical model to simulate the dynamics of heterosexual HIV transmission, including gender differences in the negotiation of safe sexual practices, in these populations. The potential impact of future HIV vaccination programs is considered, focusing on the interactions between vaccine efficacy and risk behavior change. The analysis is extended in the fourth paper by adapting the framework developed for HIV vaccines, likely not available for at least a decade, to consider adult male circumcision---another potential, partially---effective HIV prevention program for which clinical trial efficacy data have recently been released and for which the technology is available immediately

Zika, Pregnancy, and the Law

The public health emergency surrounding the spread of the Zika virus has resurrected and brought into sharp relief some of the most vexing questions surrounding the relationship between pregnancy and law: the appropriate circumstances, if any, in which fetal tissue research is permissible; when and how the government may sponsor statements intended to influence reproductive decisions; and how to balance the health and rights of both women and their unborn children when health threats target both

Dynamic Transmission Modeling:A Report of the ISPOR-SMDM Modeling Good Research Practices Task Force-5

AbstractThe transmissible nature of communicable diseases is what sets them apart from other diseases modeled by health economists. The probability of a susceptible individual becoming infected at any one point in time (the force of infection) is related to the number of infectious individuals in the population, will change over time, and will feed back into the future force of infection. These nonlinear interactions produce transmission dynamics that require specific consideration when modeling an intervention that has an impact on the transmission of a pathogen. Best practices for designing and building these models are set out in this article

Is a HIV vaccine a viable option and at what price? An economic evaluation of adding HIV vaccination into existing prevention programs in Thailand

<p>Abstract</p> <p>Background</p> <p>This study aims to determine the maximum price at which HIV vaccination is cost-effective in the Thai healthcare setting. It also aims to identify the relative importance of vaccine characteristics and risk behavior changes among vaccine recipients to determine how they affect this cost-effectiveness.</p> <p>Methods</p> <p>A semi-Markov model was developed to estimate the costs and health outcomes of HIV prevention programs combined with HIV vaccination in comparison to the existing HIV prevention programs without vaccination. The estimation was based on a lifetime horizon period (99 years) and used the government perspective. The analysis focused on both the general population and specific high-risk population groups. The maximum price of cost-effective vaccination was defined by using threshold analysis; one-way and probabilistic sensitivity analyses were performed. The study employed an expected value of perfect information (EVPI) analysis to determine the relative importance of parameters and to prioritize future studies.</p> <p>Results</p> <p>The most expensive HIV vaccination which is cost-effective when given to the general population was 12,000 Thai baht (US$1 = 34 Thai baht in 2009). This vaccination came with 70% vaccine efficacy and lifetime protection as long as risk behavior was unchanged post-vaccination. The vaccine would be considered cost-ineffective at any price if it demonstrated low efficacy (30%) and if post-vaccination risk behavior increased by 10% or more, especially among the high-risk population groups. The incremental cost-effectiveness ratios were the most sensitive to change in post-vaccination risk behavior, followed by vaccine efficacy and duration of protection. The EVPI indicated the need to quantify vaccine efficacy, changed post-vaccination risk behavior, and the costs of vaccination programs.</p> <p>Conclusions</p> <p>The approach used in this study differentiated it from other economic evaluations and can be applied for the economic evaluation of other health interventions not available in healthcare systems. This study is important not only for researchers conducting future HIV vaccine research but also for policy decision makers who, in the future, will consider vaccine adoption.</p

Literature Review - the vaccine supply chain

Vaccination is one of the most effective ways to prevent the outbreak of an infectious disease. This medical intervention also brings about many logistical quest

The impact of dual HIV and HPV vaccine strategies among adolescents in a resource constrained setting

A thesis completed by published work, Submitted to the School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, in fulfilment of the requirements for the degree of Doctor of Philosophy Johannesburg, South Africa December 2016.Introduction With the largest epidemic in the world, the consequences of human immunodeficiency virus (HIV) in South Africa extend far beyond its disease burden. In fact, patterns of HIV-related infection and mortality in South Africa still reflect social cleavages and inequalities. Similarly, poverty-related issues such as poor education, unemployment and subsequent low socio-economic status, rural residence and inadequate access to health care are all implicated in human papillomavirus (HPV) associated cervical cancer-related mortality (of which South Africa also has the highest globally). Despite the knowledge of reproductive functions and sexuality being poor among adolescents in South Africa, the majority commence their sexual activity early with an estimated national average of 15 years for girls and 14 years for boys. Further, many South African adolescents engage in sexual risk-taking behaviours including concurrent partners and unprotected sexual acts that considerably increase their vulnerability to sexually transmitted infections including HIV and HPV. In recognising the unique health needs of adolescents in South Africa, the national government has already pin-pointed school health services as a strategic arm of primary health care re-engineering. The aim of this body of work is to elaborate on restructuring of adolescent health care by introducing the HIV and HPV vaccine concomitantly in South Africa via a school-based sexual and reproductive health service. Methodology Data from four studies were analysed and are presented in three published and two unpublished papers. The first study evaluated the synergism between HIV and HPV in the South African context and formed the basis of the literature review. The second study considered HIV vaccine implementation alone. The third study assessed dual HIV and HPV vaccine strategies among females and the final study compared the dual vaccination strategy against recognised biomedical HIV prevention interventions. The studies evaluated the implementation of a hypothetical HIV vaccine and the bivalent HPV vaccine both individually and in combination when administered to school-going adolescents in South Africa. The health outcomes and the cost-effectiveness of these strategies were assessed. Assumptions were made regarding the hypothetical HIV vaccine (based on HIV vaccine studies conducted to date) including a coverage rate of 60% (uncertainty range: 30-70%), vaccine efficacy of 50% (uncertainty range: 30-70%) and vaccine price per dose of US$12 (uncertainty range: US$ 3-24). The uncertainty ranges were tested in the sensitivity analysis. Mortality statistics, disease transition parameters (for the individual diseases and the models representing joint disease) and HPV vaccine characteristics were drawn from the South African literature. The joint effectiveness of the dual vaccine strategy was considered multiplicative. Nine year old adolescents attending South African schools in 2012 were eligible for the intervention (vaccination) that was introduced opportunistically as part of the national health initiative introducing school-based sexual and reproductive health services. The learners were targeted prior to their reported sexual debut. The HIV vaccine was considered against the comparator of HIV counselling and testing (HCT) and the national roll-out of antiretroviral therapy (ART) that constituted the standard of care in South Africa. The HPV vaccine was modelled as prevention against HPV-related cervical cancer and pre-cancerous HPV-related cervical states. The health service provider (provider) perspective was adopted and the cohort was modelled through a lifetime horizon of 70 years with annual cycles. The economic costs and health outcomes were discounted at 3% with an uncertainty range between 0% and 6% assessed. Cost valuations were for 2012 and costs were adjusted to this common year. The quality-adjusted life year (QALY) was used as the outcome measure of health related quality of life and was used to calculate the incremental cost-effectiveness ratio (ICER) of the comparator against the vaccination interventions. The core model was a semi-Markov simulation with annual cycles. The study population entered the model HIV and HPV disease free and were exposed to the risk of acquiring each disease annually. The model structure was parameterised drawing from South African data available in the literature. One-way sensitivity analyses evaluated the impact of single assumptions on cost and outcomes. Probabilistic sensitivity analysis (PSA) with a bootstrapping technique explored the uncertainty in the model and evaluated the robustness of the results. The PSA data generated determined if the intervention fell below the willingness-to-pay (WTP) threshold. As South Africa does not have a pre-defined WTP threshold, the Gross Domestic Product (GDP) per capita (for 2012) was used as a proxy in accordance with the World Health Organization’s Guide to Cost-Effective Analysis. Additionally, benchmark interventions were used in the final comparison study as a measure of cost-effectiveness. Ethical approval for the study was obtained from the Human Research Ethics Committee (Medical) of the University of the Witwatersrand. Findings The second study explored the implementation of the HIV vaccine on an individual and national, programmatic level. The simultaneous implementation of HIV vaccination services with current HIV management programmes would be cost-effective, even at relatively higher vaccine cost. At base vaccine cost of US$12, the ICER was US$ 43 per QALY gained, with improved ICER values yielded at lower vaccine costs. The ICER was sensitive to the duration of vaccine-mediated protection and to variations in the vaccine efficacy. Data from this work demonstrate that vaccines offering longer duration of protection and at lower cost would result in improved ICER values. Assessing this HIV vaccine model on a national programmatic level, yielded an ICER of US$5 per life-year gained (LYG) (95$ 3-12) compared with the comparator. This fell considerably below the national WTP threshold of cost-effectiveness. This also translated to an 11% increase in per capita costs from US$80 to US$ 89. National implementation of this intervention could potentially result in an estimated cumulative gain of 24 million years of life (95% CI 8–34 million years) among those adolescents aged between 10-19 years that were vaccinated. The 10 year absolute risk reduction projected by HIV vaccine implementation was 0.42% for HIV incidence and 0.41% for HIV mortality. The ICER was sensitive to the HIV vaccine efficacy, coverage and vaccine pricing in the sensitivity analysis. The third study assessed the impact of dual HIV and HPV implementation strategies. Programmes that involved the dual vaccine strategy were assessed as cost-saving. ICER values were sensitive to the HIV vaccine cost. The dual vaccine strategy resulted in 10 year absolute risk reductions in HIV incidence (5.24%), dual mortality (1.21%) and a reduction in HPV incidence (0.39%) compared with no vaccination. Importantly, the reduction in HIV incidence rate and dual mortality rate in the dual vaccine strategy exceeded the reductions noted with the use of the HIV vaccine alone. All scenarios assessed with the dual vaccine strategy were cost-effective. Lower vaccine prices and reduced discount rates were associated with improved ICER outcomes. The final study compared the biomedical interventions of oral pre-exposure prophylaxis (PrEP), voluntary medical male circumcision (VMMC) and the scaling-up of ART coverage against the vaccine strategies. When compared with other biomedical HIV prevention interventions, the dual vaccination intervention was the most cost-effective strategy (US$7 per QALY gained) and averted 29$ 30 per QALY gained) proved more cost-effective than HIV vaccination alone (US$ 93 per QALY gained), though VMMC averted 6% more new infections than the HIV vaccine. PrEP interventions were the least cost-effective. Combined dual vaccination and VMMC strategies represent the only dominant intervention. Strategies involving oral PrEP were the least cost-effective. Conclusion The findings of this thesis have implications for school-based adolescent health care and HIV- and HPV-related disease prevention among adolescents, a highly susceptible population. The cost-effectiveness of the dual HIV and HPV vaccine strategy was demonstrated, and the improved health outcomes associated with the interventions quantified. Proposals were suggested regarding possible combinations of HIV prevention interventions that could yield the favourable health outcomes with the most efficient use of financial resources. Several important areas for future research were identified to shed light on improving adolescent health care and for optimising HIV prevention strategies. These include integrating HIV and HPV services as part of the re-engineering of primary health care in South Africa, and then formulating economic evaluations of HIV/HPV prevention strategies targeting adolescents specifically. Further, more effective methods of collecting data on socially marginalised populations such as young people need to be explored. Another vital research area is the discussion and implementation of existing school health documents with the ideals embodied in the school health programme envisaged under the National Health Insurance restructuring. Once these are integrated, the cost implication of the combined programmes need to be assessed.MT201

A stochastic multi-scale model of HIV-1 transmission for decision-making: application to a MSM population.

BackgroundIn the absence of an effective vaccine against HIV-1, the scientific community is presented with the challenge of developing alternative methods to curb its spread. Due to the complexity of the disease, however, our ability to predict the impact of various prevention and treatment strategies is limited. While ART has been widely accepted as the gold standard of modern care, its timing is debated.ObjectivesTo evaluate the impact of medical interventions at the level of individuals on the spread of infection across the whole population. Specifically, we investigate the impact of ART initiation timing on HIV-1 spread in an MSM (Men who have Sex with Men) population.Design and methodsA stochastic multi-scale model of HIV-1 transmission that integrates within a single framework the in-host cellular dynamics and their outcomes, patient health states, and sexual contact networks. The model captures disease state and progression within individuals, and allows for simulation of therapeutic strategies.ResultsEarly ART initiation may substantially affect disease spread through a population.ConclusionsOur model provides a multi-scale, systems-based approach to evaluate the broader implications of therapeutic strategies