PIN22 Cost-Effectiveness of Hepatitis a Vaccination in Indonesia

Objectives: This study aims to assess the cost-effectiveness of hepatitis A vaccination in Indonesia, including an explicit comparison between one-dose and twodose vaccines. Methods: An age-structured cohort model based on a decision tree was developed for the 2012 Indonesia birth cohort. Using the model, we made a comparison on the use of two-dose and one-dose vaccines. The model involves a 70-year time horizon with 1-month cycles for children less than 2 years old and annually thereafter. Monte Carlo simulations were used to examine the economic acceptability and affordability of the hepatitis A vaccination. Results: With the vaccine price of US$4.49 per dose, the implementation of the hepatitis A vaccine from the societal perspective would yield incremental-cost-effectiveness-ratios (ICERs) at US$ 9,194 and US$4,577 for the two-dose and one-dose vaccine schedules, respectively. Considering the 2012 gross-domestic-product (GDP) per capita in Indonesia of US$ 3,557, the results indicate that hepatitis A vaccination would be a cost-effective intervention, both for the two-dose and one-dose vaccine schedules. Vaccination would be 100% affordable at budgets of US$89,918,000 and US$ 46,778,000 for the implementation of the two-dose and one-dose vaccine schedules, respectively. Conclusions: The implementation of hepatitis A vaccination in Indonesia would be a cost-effective health intervention under the market vaccine prices. Given the budget limitations, the use of a one-dose-vaccine schedule would be more realistic to be applied than a two-dose schedule. The discount rate, vaccine price, vaccine efficacy and mortality rate were the most influential parameters impacting the ICERs

A computationally efficient method for probabilistic parameter threshold analysis for health economic evaluations

Background. Threshold analysis is used to determine the threshold value of an input parameter at which a health care strategy becomes cost-effective. Typically, it is performed in a deterministic manner, in which inputs are varied one at a time while the remaining inputs are each fixed at their mean value. This approach will result in incorrect threshold values if the cost-effectiveness model is nonlinear or if inputs are correlated. Objective. To propose a probabilistic method for performing threshold analysis, which accounts for the joint uncertainty in all input parameters and makes no assumption about the linearity of the cost-effectiveness model. Methods. Three methods are compared: 1) deterministic threshold analysis (DTA); 2) a 2-level Monte Carlo approach, which is considered the gold standard; and 3) a regression-based method using a generalized additive model (GAM), which identifies threshold values directly from a probabilistic sensitivity analysis sample. Results. We applied the 3 methods to estimate the minimum probability of hospitalization for typhoid fever at which 3 different vaccination strategies become cost-effective in Uganda. The threshold probability of hospitalization at which routine vaccination at 9 months with catchup campaign to 5 years becomes cost-effective is estimated to be 0.060 and 0.061 (95% confidence interval [CI], 0.058–0.064), respectively, for 2-level and GAM. According to DTA, routine vaccination at 9 months with catchup campaign to 5 years would never become cost-effective. The threshold probability at which routine vaccination at 9 months with catchup campaign to 15 years becomes cost-effective is estimated to be 0.092 (DTA), 0.074 (2-level), and 0.072 (95% CI, 0.069–0.075) (GAM). GAM is 430 times faster than the 2-level approach. Conclusions. When the cost-effectiveness model is nonlinear, GAM provides similar threshold values to the 2-level Monte Carlo approach and is computationally more efficient. DTA provides incorrect results and should not be used

Hepatitis B prevention in Europe: a preliminary economic evaluation

The World Health Organization (WHO) estimates that about 350 million people in the world are carriers of the hepatitis B virus (HBV), 60 million of whom may die from liver cancer and about 45 million from cirrhosis. In the WHO European Region, which has a total population of 839 million inhabitants, the average number of acute hepatitis B cases reported in 1991 was approximately 160 000, giving an incidence of 19 per 100 000 population. This incidence rate varies from 5 per 100 000 in western Europe to 22 per 100 000 in central Europe and 92 per 100 000 in eastern Europe. Because of under-reporting and the fact that two-thirds of infections are asymptomatic, the reported incidence rate considerably underestimates the true incidence of HBV in Europe. For this reason, we may multiply the number of reported cases by a factor of 6 (by 2 for under-reporting and by 3 for the symptomatic/asymptomatic ratio): an estimated 900 000 to 1 000 000 infections of HBV occur in Europe each year. Approximately 90 000 chronic infections will develop from these new cases. The spread of HBV can be controlled by universal infant or adolescent vaccination. A decision-tree-based analytical model was used to assess the clinical and economic impact of these two interventions. The model took into account incidence and prevalence rates of HBV, natural history of infection, compliance and effectiveness of vaccination, and direct and indirect costs. Data were obtained from the literature and from a WHO European survey. The cost-effectiveness ratio amounts to £6443 and £4745 per infection prevented for neonatal and adolescent vaccination, respectively. The results from these calculations show that neither vaccination of neonates or of adolescents is cost-saving. However, the cost-effectiveness - i.e. the cost incurred to prevent an HBV infection is of an acceptable magnitude for both strategies

Priority-Setting and Personality

In a publicly fnanced health system, it is important that priority-setting refects social values. Many studies investigate public preferences through surveys taken from samples, but to be representative, these samples must refect value judgments of all relevant population subgroups. In this study, we explore whether, next to better-understood sources of heterogeneity such as age, education or gender, also diferences in personality play a role in how people want to set limits to health care. We investigate the infuence of dispositional optimism: whether someone anticipates a good or bad future. This is an important personality dimension that has been shown to widely reverberate into people’s lives and that can also be expected to infuence people’s views on health care. To test our hypothesis, we asked a representative sample of the Belgian population (N=750) to complete both the revised life orientation test and a discrete choice experiment about allocating healthcare resources, and we investigated the relationships between both measurements. We found that more pessimistic individuals were less supportive of using patients’ age as a selection criterion and more hesitant to invest in prevention. Since individual dispositions are usually not part of the criteria for selecting representative samples, our fndings point at a potential non-response bias in studies that elicit social values

The age profile of respiratory syncytial virus burden in preschool children of low- and middle-income countries: a semi-parametric, meta-regression approach

BACKGROUND: Respiratory syncytial virus (RSV) infections are among the primary causes of death for children under 5 years of age worldwide. A notable challenge with many of the upcoming prophylactic interventions against RSV is their short duration of protection, making the age profile of key interest to the design of prevention strategies. METHODS AND FINDINGS: We leverage the RSV data collected on cases, hospitalizations, and deaths in a systematic review in combination with flexible generalized additive mixed models (GAMMs) to characterize the age burden of RSV incidence, hospitalization, and hospital-based case fatality rate (hCFR). Due to the flexible nature of GAMMs, we estimate the peak, median, and mean incidence of infection to inform discussions on the ideal "window of protection" of prophylactic interventions. In a secondary analysis, we reestimate the burden of RSV in all low- and middle-income countries. The peak age of community-based incidence is 4.8 months, and the mean and median age of infection is 18.9 and 14.7 months, respectively. Estimating the age profile using the incidence coming from hospital-based studies yields a slightly younger age profile, in which the peak age of infection is 2.6 months and the mean and median age of infection are 15.8 and 11.6 months, respectively. More severe outcomes, such as hospitalization and in-hospital death have a younger age profile. Children under 6 months of age constitute 10% of the population under 5 years of age but bear 20% to 29% of cases, 28% to 39% of hospitalizations, and 38% to 50% of deaths. On an average year, we estimate 28.23 to 31.34 million cases of RSV, between 2.95 to 3.35 million hospitalizations, and 16,835 to 19,909 in-hospital deaths in low, lower- and upper middle-income countries. In addition, we estimate 17,254 to 23,875 deaths in the community, for a total of 34,114 to 46,485 deaths. Globally, evidence shows that community-based incidence may differ by World Bank Income Group, but not hospital-based incidence, probability of hospitalization, or the probability of in-hospital death (p ≤ 0.01, p = 1, p = 0.86, 0.63, respectively). Our study is limited mainly due to the sparsity of the data, especially for low-income countries (LICs). The lack of information for some populations makes detecting heterogeneity between income groups difficult, and differences in access to care may impact the reported burden. CONCLUSIONS: We have demonstrated an approach to synthesize information on RSV outcomes in a statistically principled manner, and we estimate that the age profile of RSV burden depends on whether information on incidence is collected in hospitals or in the community. Our results suggest that the ideal prophylactic strategy may require multiple products to avert the risk among preschool children

Exploratory Analysis of the Economically Justifiable Price of a Hypothetical RSV Vaccine for Older Adults in the Netherlands and the United Kingdom

BACKGROUND: In older adults, the burden of respiratory syncytial virus (RSV) resembles that of influenza and may even be considered worse due to the lack of preventive interventions. This study was performed to identify the available literature on RSV infection in older adults, and to provide updated exploratory results of the cost-effectiveness of a hypothetical RSV vaccine in the Netherlands and the United Kingdom. METHODS: A literature search was performed in Medline and EMBASE on 11 November 2019, which served as input for a static decision-tree model that was used to estimate the EJP, for an RSV vaccine applying different willingness-to-pay (WTP) thresholds. WTP thresholds applied were €20 000 and €50 000 per quality-adjusted life-year for the Netherlands, and £20 000 and £30 000 per quality-adjusted life-year for the United Kingdom. Analyses were—in line with country-specific guidelines—conducted from a societal perspective for the Netherlands and a third-party payer perspective for the United Kingdom. The robustness of the cost-effectiveness results was tested in sensitivity analysis. RESULTS: After screening the literature, 3 studies for the Netherlands and 6 for the United Kingdom remained to populate the country-specific models. In the base case analysis for the Netherlands (mean RSV incidence, 3.32%), justifiable vaccine prices of €16.38 and €50.03 were found, based on applying the lower and higher WTP thresholds, respectively. Similarly, for the United Kingdom (mean incidence, 7.13%), vaccine prices of £72.29 and £109.74 were found, respectively. CONCLUSION: RSV vaccination may well be cost-effective in both the Netherlands and the United Kingdom, depending on the exact RSV incidence, vaccine effectiveness and price. However, sensitivity analysis showed that the results were robust based on varying the different parameter estimates and assumptions. With RSV vaccines reaching the final stages of development, a strong need exists for cost-effectiveness studies to understand economically justifiable pricing of the vaccine

The importance of including dynamic social networks when modeling epidemics of airborne infections: does increasing complexity increase accuracy?

Mathematical models are useful tools for understanding and predicting epidemics. A recent innovative modeling study by Stehle and colleagues addressed the issue of how complex models need to be to ensure accuracy. The authors collected data on face-to-face contacts during a two-day conference. They then constructed a series of dynamic social contact networks, each of which was used to model an epidemic generated by a fast-spreading airborne pathogen. Intriguingly, Stehle and colleagues found that increasing model complexity did not always increase accuracy. Specifically, the most detailed contact network and a simplified version of this network generated very similar results. These results are extremely interesting and require further exploration to determine their generalizability

Different forms of superspreading lead to different outcomes:heterogeneity in infectiousness and contact behavior relevant for the case of SARS-CoV-2

Superspreading events play an important role in the spread of several pathogens, such as SARS-CoV-2. While the basic reproduction number of the original Wuhan SARS-CoV-2 is estimated to be about 3 for Belgium, there is substantial inter-individual variation in the number of secondary cases each infected individual causes—with most infectious individuals generating no or only a few secondary cases, while about 20% of infectious individuals is responsible for 80% of new infections. Multiple factors contribute to the occurrence of superspreading events: heterogeneity in infectiousness, individual variations in susceptibility, differences in contact behavior, and the environment in which transmission takes place. While superspreading has been included in several infectious disease transmission models, research into the effects of different forms of superspreading on the spread of pathogens remains limited. To disentangle the effects of infectiousness-related heterogeneity on the one hand and contact-related heterogeneity on the other, we implemented both forms of superspreading in an individual-based model describing the transmission and spread of SARS-CoV-2 in a synthetic Belgian population. We considered its impact on viral spread as well as on epidemic resurgence after a period of social distancing. We found that the effects of superspreading driven by heterogeneity in infectiousness are different from the effects of superspreading driven by heterogeneity in contact behavior. On the one hand, a higher level of infectiousness-related heterogeneity results in a lower risk of an outbreak persisting following the introduction of one infected individual into the population. Outbreaks that did persist led to fewer total cases and were slower, with a lower peak which occurred at a later point in time, and a lower herd immunity threshold. Finally, the risk of resurgence of an outbreak following a period of lockdown decreased. On the other hand, when contact-related heterogeneity was high, this also led to fewer cases in total during persistent outbreaks, but caused outbreaks to be more explosive in regard to other aspects (such as higher peaks which occurred earlier, and a higher herd immunity threshold). Finally, the risk of resurgence of an outbreak following a period of lockdown increased. We found that these effects were conserved when testing combinations of infectiousness-related and contact-related heterogeneity

Cost effectiveness of pediatric pneumococcal conjugate vaccines: a comparative assessment of decision-making tools

BACKGROUND: Several decision support tools have been developed to aid policymaking regarding the adoption of pneumococcal conjugate vaccine (PCV) into national pediatric immunization programs. The lack of critical appraisal of these tools makes it difficult for decision makers to understand and choose between them. With the aim to guide policymakers on their optimal use, we compared publicly available decision-making tools in relation to their methods, influential parameters and results. METHODS: The World Health Organization (WHO) requested access to several publicly available cost-effectiveness (CE) tools for PCV from both public and private provenance. All tools were critically assessed according to the WHO's guide for economic evaluations of immunization programs. Key attributes and characteristics were compared and a series of sensitivity analyses was performed to determine the main drivers of the results. The results were compared based on a standardized set of input parameters and assumptions. RESULTS: Three cost-effectiveness modeling tools were provided, including two cohort-based (Pan-American Health Organization (PAHO) ProVac Initiative TriVac, and PneumoADIP) and one population-based model (GlaxoSmithKline's SUPREMES). They all compared the introduction of PCV into national pediatric immunization program with no PCV use. The models were different in terms of model attributes, structure, and data requirement, but captured a similar range of diseases. Herd effects were estimated using different approaches in each model. The main driving parameters were vaccine efficacy against pneumococcal pneumonia, vaccine price, vaccine coverage, serotype coverage and disease burden. With a standardized set of input parameters developed for cohort modeling, TriVac and PneumoADIP produced similar incremental costs and health outcomes, and incremental cost-effectiveness ratios. CONCLUSIONS: Vaccine cost (dose price and number of doses), vaccine efficacy and epidemiology of critical endpoint (for example, incidence of pneumonia, distribution of serotypes causing pneumonia) were influential parameters in the models we compared. Understanding the differences and similarities of such CE tools through regular comparisons could render decision-making processes in different countries more efficient, as well as providing guiding information for further clinical and epidemiological research. A tool comparison exercise using standardized data sets can help model developers to be more transparent about their model structure and assumptions and provide analysts and decision makers with a more in-depth view behind the disease dynamics. Adherence to the WHO guide of economic evaluations of immunization programs may also facilitate this process. Please see related article: http://www.biomedcentral.com/1741-7007/9/55

Influence of Contact Definitions in Assessment of the Relative Importance of Social Settings in Disease Transmission Risk

BACKGROUND: Realistic models of disease transmission incorporating complex population heterogeneities require input from quantitative population mixing studies. We use contact diaries to assess the relative importance of social settings in respiratory pathogen spread using three measures of person contact hours (PCH) as proxies for transmission risk with an aim to inform bipartite network models of respiratory pathogen transmission. METHODS AND FINDINGS: Our survey examines the contact behaviour for a convenience sample of 65 adults, with each encounter classified as occurring in a work, retail, home, social, travel or "other" setting. The diary design allows for extraction of PCH-interaction (cumulative time in face-face conversational or touch interaction with contacts)--analogous to the contact measure used in several existing surveys--as well as PCH-setting (product of time spent in setting and number of people present) and PCH-reach (product of time spent in setting and number of people in close proximity). Heterogeneities in day-dependent distribution of risk across settings are analysed using partitioning and cluster analyses and compared between days and contact measures. Although home is typically the highest-risk setting when PCH measures isolate two-way interactions, its relative importance compared to social and work settings may reduce when adopting a more inclusive contact measure that considers the number and duration of potential exposure events. CONCLUSIONS: Heterogeneities in location-dependent contact behaviour as measured by contact diary studies depend on the adopted contact definition. We find that contact measures isolating face-face conversational or touch interactions suggest that contact in the home dominates, whereas more inclusive contact measures indicate that home and work settings may be of higher importance. In the absence of definitive knowledge of the contact required to facilitate transmission of various respiratory pathogens, it is important for surveys to consider alternative contact measures