Cost effectiveness of prophylactic HPV 16/18 vaccination in Finland: results from a modelling exercise

Objectives: the study aims to estimate the clinical-impact and cost-effectiveness value of adding human papillomavirus 16/18 vaccination against cervical cancer among women currently undergoing organised screening in Finland.

Methods: A Markov cohort model evaluating high-risk HPV infections and cervical cancer (CC) cases combined with screening has been customised to the Finnish setting. The model outcome for a cohort of 30,000 girls aged 10 years was calibrated to age-specific annual number of Pap smears, CC incidence and mortality.

Results: The observed age-specific incidence and mortality rates of CC closely match the data replicated by the model. The model predicts that with a 90% vaccine coverage rate, CC cases and mortality would be reduced by 70%. In the base-case analysis with a discount rate of 3% the incremental cost per quality-adjusted life-years (QALY) gained, from a healthcare perspective, was €17,294. Without discounting this value is €2,591/QALY gained.

Conclusions: The analysis suggests that implementing prophylactic CC vaccination within the current screening system would substantially reduce CC cases and deaths, as well as the overall disease burden expressed in pre-cancer lesions averted. Vaccination could be a cost-effective intervention in Finland despite the fact that the number of CC cases and deaths are currently relatively low. Conservative estimates of the cost effectiveness of the vaccination were provided since it was not possible to assess herd protection induced by vaccination using this Markov model.     

The cost effectiveness of a quadrivalent human papillomavirus vaccine (6/11/16/18) in Hungary

Abstract

Objective: A transmission dynamic model was used to assess the epidemiological and economic impact of a quadrivalent human papillomavirus (HPV) (6/11/16/18) vaccine in preventing cervical cancer, cervical intraepithelial neoplasia grades 2 and 3 (CIN 2/3), CIN 1 and genital warts in Hungary.

Methods: The routine vaccination of 12-year-old girls and the routine vaccination of 12-year-old girls plus a temporary catch-up programme for girls and women aged 12–24 years was evaluated.

Results: The model projected that at year 100, both strategies could reduce the incidence of HPV 6/11/16/18-related cervical cancer, CIN 2/3, CIN 1 and genital warts cases among Hungarian women by 90%, 90%, 85% and 93%, respectively. Twenty-five years after the introduction of HPV vaccination in the population, routine vaccination of girls by the age of 12 reduced the cumulative number of cases of cervical cancer, CIN 2/3, CIN 1 and genital warts by 685, 13,473, 3,423 and 163,987, respectively. The incremental cost-effectiveness ratios of the two vaccination strategies were €9,577 and €10,646 per quality-adjusted life-year (QALY) gained over a time horizon of 100 years.

Key limitations: The model did not account for the health and economic impact of other HPV diseases which may result from HPV 16, 18, 6, and 11 infections such as vaginal, vulvar, penile, anal and head-neck cancers, and recurrent respiratory papillomatosis. Epidemiological data from Hungary on these other HPV diseases as well genital warts are needed.

Conclusion: A quadrivalent HPV vaccination programme can reduce the incidence of cervical cancer, CIN and genital warts in Hungary at a cost-per-QALY ratio within the range defined as cost effective.     

Stable International Environmental Agreements: An Analytical Approach

In this paper we examine the formation of international environmental agreements (IEAs). We show that the welfare of the signatories does not increase monotonically with respect to the number of signatories. We provide an analytical solution of the leadership model. In particular, we find that if the number of countries is greater than four then there exists a unique stable IEA with either two, three, or four signatories. Furthermore, we show that the welfare of the signatories is almost at its lowest level when the IEA is stable. While in our model each country's choice variable is emissions, we extend our results to the case where the choice variable is abatement efforts.     

Hybrid Contests

This paper examines hybrid contests where participants commit two types of resources to improve their probability of winning the prize. The first type is forfeited ex ante, before the prize is allocated, by winners and losers alike, while the second is committed ex ante by all contenders but expended ex post, after the prize is allocated, and only by the contestant that wins the prize. The model yields a number of interesting results. Among them is the finding that, as the number of contestants increases, the ex ante expenditures of individual contestants decrease while the ex post expenditure increases. Even more interesting, the total of the ex ante and ex post expenditures by the contenders in a hybrid contest may decrease with the number of competitors. The study also finds that there is no rent overdissipation, and compares the total expenditures in the contest and “all‐pay” allocation mechanisms.     

Coordination, “Magic,” and Reinforcement Learning in a Market Entry Game

Previous experimental studies have documented quick convergence to equilibrium play in market entry games with a large number of agents. The present study examines the effect of the available information in a 12-player game in an attempt to account for these findings. In line with the prediction of a simple reinforcement learning model (Roth and Erev, 1995,Games Econ. Behav.8, 164–212), quick convergence to equilibrium is observed even given minimal information (unknown payoff rule). However, in violation of the basic model, information concerning other players' payoff increases the number of entrants. The information effect can be described by a variant of the basic reinforcement learning model assuming that the additional information changes the player's reference point.Journal of Economic LiteratureClassification Number: C7, C92.     

Burden of rotavirus gastroenteritis and potential benefits of a pentavalent rotavirus vaccination in Belgium

Abstract

Objective and Methods: A decision analytic model was built to assess the paediatric rotavirus gastroenteritis (RVGE) burden and potential benefits associated with the introduction of RotaTeq^®? (pentavalent rotavirus vaccine) in Belgium.

Results: In the absence of a rotavirus (RV) immunisation programme, paediatric RVGE was estimated to account for about 5,860 hospitalisations, 1,720 cases of nosocomial infections, 9,410 cases treated by general practitioners/paediatricians (GP/P) and 10,790 cases not seeking medical care for a birth cohort followed up to 5 years of age. Paediatric RVGE was estimated to cost about €9.0 million from the Belgian healthcare provider perspective and €15.3 million to society. Given a 90% RV vaccination coverage rate, the pentavalent RV vaccine would have a high impact on RV burden by preventing more than 4,850 hospitalisations, 995 cases of nosocomial infections, 7,145 cases treated by GP/P and 8,190 cases not seeking medical care, and reduce RVGE costs by €7.1 million from the Belgian healthcare provider perspective and €12.0 million to society.     

Cyclicality and Sectoral Linkages: Aggregate Fluctuations from Independent Sectoral Shocks

The traditional argument against the relevance of sector-specific shocks for the aggregate phenomenon of business cycles invokes the law of large numbers: positive shocks in some sectors are offset by negative shocks in other sectors. This paper hypothesizes that cancellation of sector-specific shocks via the law of large numbers is affected by interactions among producing sectors. The analysis is performed within the context of a multisector model similar in spirit to that of Long and Plosser [J. Polit. Econ.91(1983), 39–69]. It is shown that the rate at which the law of large numbers applies is controlled by the rate of increase in the number offullrows in the input-use matrix rather than by the rate of increase in the total number of sectors. Investigations of actual input-use matrices from the U.S. economy reveal that the number of full rows increases much slower than the total number of rows upon disaggregation, and when these input-use matrices are used to parameterize the model, aggregate volatility from sectoral shocks declines at less than half the rate implied by the law of large numbers. This finding leaves open the possibility that a sizeable portion of aggregate volatility is caused by “smaller” shocks to individual sectors. Simple statistics calculated from the model indicate that as much as 80% the volatility in U.S. gross domestic product growth rates could be the result of independent shocks to two-digit Standard Industrial Code sectors.Journal of Economic LiteratureClassification Numbers: E1, E32, C67.     

Cost effectiveness of palivizumab for RSV prevention in high-risk children in the Netherlands

Abstract

Background: Respiratory syncytial virus (RSV) is a common pathogen that is the leading cause of lower respiratory tract infections in young children. High-risk children are at risk of severe infection, which may require hospitalisation. RSV is also associated with a high risk for respiratory morbidity and mortality, which may have long-term clinical and economic consequences.

Objective: To assess the cost effectiveness of palivizumab, a humanised monoclonal antibody, used as prevention against severe respiratory syncytial virus (RSV) infection requiring hospitalisation, in the indication of preterm infants and infants with preterm/bronchopulmonary dysplasia and in the second indication of children with congenital heart disease in the Dutch healthcare setting.

Methods: A decision-tree model was used to estimate the cost effectiveness of palivizumab, used as a preventative treatment against severe respiratory syncytial virus (RSV) infection, in high-risk groups of children in the Netherlands. The analysis was based on a lifetime follow-up period in order to capture the impact of palivizumab on long-term morbidity and mortality resulting from an RSV infection. Data sources included published literature, the palivizumab pivotal trials, official price/tariff lists and national population statistics. The study was conducted from the perspective of society in the Netherlands.

Results: The use of palivizumab results in undiscounted incremental cost-effectiveness ratios of €12,728/QALY and €4,256/QALY in the in preterm/bronchopulmonary dysplasia and congenital heart disease indications, respectively. Inclusion of indirect costs leads to even more favourable cost-effectiveness outcomes. The study is limited by a number of conservative assumptions. It was assumed that palivizumab only affects the occurrence of RSV hospitalisation and does not influence the severity of the RSV infection. Another assumption was that international clinical trial data and data on utilities could be applied to the Dutch healthcare setting.

Conclusion: Palivizumab provides cost-effective prophylaxis against RSV in high-risk infants. The use of palivizumab in these children results in positive short- and long-term health-economic benefits.     

Identifying cost-effective screening algorithms for active hepatitis C virus infections in a high prevalence setting

Objective: To evaluate the cost-effectiveness of different screening patterns for active chronic hepatitis C virus (HCV) infections utilizing the hepatitis C core antigen test compared to standard care in the context of a general screening program in a high-prevalence country.

Methods: This study developed a decision analytic model to estimate the cost-effectiveness of four screening algorithms for the detection of active HCV infections among asymptomatic individuals with an unknown HCV status in a context of high (>5%) HCV prevalence. Three algorithms started with a serological test for antibodies (AB) followed by a nucleic acid test for HCV-RNA (RNA), the HCVAg (AG) assay, or both. An additional single marker screening strategy with AG was added to the analysis. By the example of the Republic of Georgia, strategies were compared in terms of total costs for screening and diagnosis of an active infection from a health system perspective.

Results: Replacing RNA with AG for confirmation of positive AB identified fewer active infections (–110 per 100,000 screened subjects) at significantly reduced total costs (–$2.74 per screened) and costs per diagnosed infection (–$44). Adding a subsequent RNA confirmatory test on AG negative results captured at least the same rate compared to the standard (AB followed by RNA) at still reduced costs (–$1.16 per subject screened, –$22 per case detected). Utilizing AG as the frontline test revealed the highest detection rate (97.9%) at the highest costs (+$3.80 per subject, +$323 per case detected vs standard).

Conclusion: A combined pattern of HCV AB screening followed by sequential confirmation with AG and RNA on AG negatives would provide equal or better diagnostic performance at lower cost over a broad range of scenarios. Potential long-term consequences of screening strategies to patients and society have to be considered, since the latency period for HCV to develop into severe liver disease is long.     

Development of a Fuzzy optimization model,supporting global warming decision-making

An increasing number of models have been developed to support global warming response policies. The model constructors are facing a lot of uncertainties which limit the evidence of these models. The support of climate policy decision-making is only possible in a semi-quantitative way, as presented by aFuzzy model. The model design is based on an optimization approach, integrated in a bounded risk decision-making framework. Given some regional emission-related and impact-related restrictions, optimal emission paths can be calculated. The focus is not only on carbon dioxide but on other greenhouse gases too. In the paper, the components of the model will be described. Cost coefficients, emission boundaries and impact boundaries are represented asFuzzy parameters. TheFuzzy model will be transformed into a computational one by using an approach of Rommelfanger. In the second part, some problems of applying the model to computations will be discussed. This includes discussions on the data situation and the presentation, as well as interpretation of results of sensitivity analyses. The advantage of theFuzzy approach is that the requirements regarding data precision are not so strong. Hence, the effort for data acquisition can be reduced and computations can be started earlier.     

Trade protection and balance of payments problems

A model to be used for planning short-term in-patient medical care is presented. The individual clinic is treated as a production unit which produces different kinds of treated wardcases with a given technique of production (given production-cost-structure). It is assumed to maximize the yearly number of treated wardcases under the constraints of (1) The yearly demand for different kinds of treated wardcases, which is assumed to be proportional to the number of citizens within the area which the clinic serves (the clinics population), (2) The yearly budget which is assigned by public authorities and has to cover all costs as the medical care is supplied free of charge, (3) The clinics physical capacity, measured by the number of beds.

The model has been applied to the branch of general medicine using the estimated production-cost-structure at an existing clinic within this branch. The kind of information that one can get is illustrated, for example: Given a clinic with a certain technique of production (production-cost-structure) which optimizes its production in the way that the model assumes, what is the marginal effects of changes in the size of budget, physical capacity or the size of population? In the case of an existing clinic, perhaps it serves too big a population (the marginal effect of reducing this constraint is zero)? or, when establishing a given kind of clinic what is the best combination of population size, size of budget and physical capacity? How much of the demand will be unsatisfied with different combinations, i.e. how large will the queues become?     

Cycles and multiple equilibria in the market for durable lemons

Summary. The paper investigates the nature of market failure in a dynamic version of Akerlof (1970) where identical cohorts of a durable good enter the market over time. In the dynamic model, equilibria with qualitatively different properties emerge. Typically, in equilibria of the dynamic model, sellers with higher quality wait in order to sell and wait more than sellers of lower quality. The main result is that for any distribution of quality there exist an infinite number of cyclical equilibria where all goods are traded within a certain number of periods after entering the market. Received: December 21, 2000; revised version: September 5, 2001     

Health and economic impact of PHiD-CV in Canada and the UK: a Markov modelling exercise

Abstract

Objective:

The spectrum of diseases caused by Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) represents a large burden on healthcare systems around the world. Meningitis, bacteraemia, community-acquired pneumonia (CAP), and acute otitis media (AOM) are vaccine-preventable infectious diseases that can have severe consequences. The health economic model presented here is intended to estimate the clinical and economic impact of vaccinating birth cohorts in Canada and the UK with the 10-valent, pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) compared with the newly licensed 13-valent pneumococcal conjugate vaccine (PCV-13).

Methods:

The model described herein is a Markov cohort model built to simulate the epidemiological burden of pneumococcal- and NTHi-related diseases within birth cohorts in the UK and Canada. Base-case assumptions include estimates of vaccine efficacy and NTHi infection rates that are based on published literature.

Results:

The model predicts that the two vaccines will provide a broadly similar impact on all-cause invasive disease and CAP under base-case assumptions. However, PHiD-CV is expected to provide a substantially greater reduction in AOM compared with PCV-13, offering additional savings of Canadian $9.0 million and £4.9 million in discounted direct medical costs in Canada and the UK, respectively.

Limitations:

The main limitations of the study are the difficulties in modelling indirect vaccine effects (herd effect and serotype replacement), the absence of PHiD-CV- and PCV-13-specific efficacy data and a lack of comprehensive NTHi surveillance data. Additional limitations relate to the fact that the transmission dynamics of pneumococcal serotypes have not been modelled, nor has antibiotic resistance been accounted for in this paper.

Conclusion:

This cost-effectiveness analysis suggests that, in Canada and the UK, PHiD-CV’s potential to protect against NTHi infections could provide a greater impact on overall disease burden than the additional serotypes contained in PCV-13.     

Market access in regulated and unregulated markets: The continuing cost of interstate motor carrier regulation

This study examines the effect of regulatory reform in the interstate trucking industry. In our model, carriers travel in round trips and choose to serve different markets corresponding to each leg of the trip. Some carriers have authority to haul freight subject to regulation while other carriers do not. Unlike previous studies, our model applies to decisions acrossmultiple legs. Using a bivariate probit, we find differences in the determinants of accessacross markets. Entry regulation has a significant influence only in markets dominated by regulated traffic, whereas location has a significant influence only in markets dominated by unregulated traffic.Name order was determined by a coin toss. Kenneth Boyer, Victoria Dailey, Gregory Duncan, Jo Anna Gray, Shane Greenstein, Edward H. Rastatter, and Joe A. Stone made a number of useful comments that improved the paper, and Marylynne Diggs made a number of editorial comments.     

A MARKET WITH A SOCIAL CONSUMPTION EXTERNALITY*

We model a spatial market in which the utility of each consumer is affected by the consumers who buy precisely the same product. The marginal contribution of consumers x's purchase on consumer y depends on |x–y|, which declines as |x–y| increases. Such modelling of preferences fits goods that signal a consumer's place in society—clothing styles, automobiles and jewellry are examples. For 2n + 1 firms we find the unique symmetric equilibrium and derive comparative statics on the optimal number of firms, the largest number of firms the market can support, and the behaviour of profits per firm as n increases.     

A 4D natural selection model illuminates the enigma of altruism in the Shedao pit viper

Endemic to a small island off the coast of China, the Shedao pit viper, Gloydius shedaoensis, is known for its ‘accidental altruism.’ Juvenile pit vipers often kill passerine birds too large to swallow. Large prey carcasses are scavenged by neighboring adults. In turn, adult pit vipers kill hawks that prey on juvenile pit-vipers, but are not a threat to the adults themselves. Using agent-based computer simulations, we quantified the lifetime fitness of pit viper breeders with one of three genotypes: selfish, altruistic or both selfish and altruistic. Our simulation was based on a four-dimensional (4D) model of social behavior which included interactions of pit viper offspring with predators and prey as well as conspecifics. Results showed that, over ten breeding seasons, pit viper breeders with flexible altruistic and selfish genotypes averaged seven times the number of surviving offspring relative to breeders with pure-selfish genotypes, and 23 times the number of surviving offspring as breeders with pure-altruistic genotypes. In summary, viewing animal behavior through the lens of the 4D model will extend our understanding of the evolutionary pathway to social behaviors through natural selection processes.     

Contests with a stochastic number of players

We study Tullock's (1980) n-player contest when each player has an independent probability 0 < p 1 of participating. A unique symmetric equilibrium is found for any n and p and its properties are analyzed. In particular, we show that for a fixed n > 2 individual equilibrium spending as a function of p is single-peaked and satisfies a single-crossing property for any two different numbers of potential players. However, total equilibrium spending is monotonically increasing in p and n. We also demonstrate that ex-post over-dissipation is a feature of the pure-strategy equilibrium in our model. It turns out that if the contest designer can strategically decide whether to reveal the actual number of participating players or not, then the actual number of participants is always revealed.     

The indeterminacy of equilibrium city formation under monopolistic competition and increasing returns

We study the indeterminacy of equilibrium in the Fujita–Krugman [When is the economy monocentric?: von Thünen and Chamberlin unified, Reg. Sci. Urban Econ. 25 (1995) 505–528] model of city formation under monopolistic competition and increasing returns. Both the number and the locations of cities are endogenously determined. Assuming smooth transportation costs, we examine equilibria in city-economies where a finite number of cities form endogenously. For any positive integer K, the set of equilibria with K distinct cities has a smooth manifold of dimension K-1 as its interior for almost all parameter values in a regular parameterization. The disjoint union of these sets over all positive integers K constitutes the entire equilibrium set.     

A new model to evaluate the long-term cost effectiveness of orphan and highly specialised drugs following listing on the Australian Pharmaceutical Benefits Scheme: the Bosentan Patient Registry

Abstract

Background: Pharmaceutical subsidy schemes are under increasing pressure to evaluate the cost effectiveness of new highly specialised and orphan drugs for universal subsidy. In the absence of longer-term outcome data, drug sponsors often present modelled data, which can carry a significant level of uncertainty over longer-term projections. Risk-sharing schemes between drug sponsor and government may provide an acceptable method of balancing the uncertainty of longer-term cost effectiveness with the public demand for equitable and timely access to new drugs.

Methods: The Bosentan Patient Registry (BPR) is an example of a unique risk-sharing model utilised in Australia aiming to provide clinical evidence to support the modelled predictions, with the registry survival outcomes linked to future price. Concomitant medication, health and vital status data was collected from clinicians, government health departments and death registries.

Results: The BPR has identified a number of issues surrounding registry governance, ethics and patient privacy, and the collection of timely and accurate data, which need to be addressed for the development of a generic registry model for systematic evaluation.

Conclusion: The success of a generic drug registry model based on the BPR will be enhanced by addressing a number of operational issues identified during the implementation of this project.

Material in this paper was presented in an oral presentation to the National Medicines Symposium: Quality Use of Medicines, 7–9 June 2006, Canberra, Australia.     

N-PERSON NASH BNARGAINING WITH VARIABEL THREATS*

We consider two models of n-person bargaining problems with the endogenous determination of disagreement points. In the first model, which is a direct extension of Nash's variable threat bargaining model, the disagreement point is determined as an equilibrium threat point. In the second model, the disagreement point is given as a Nash equilibrium of the underlying noncooperative game. These models are formulated as extensive games, and axiomatizations of solutions are given for both models. It is argued that for games with more than two players, the first bargaining model does not preserve some important properties valid for two-person games, e.g., the uniqueness of equilibrium payoff vector. We also show that when the number of players is large, any equilibrium threat point becomes approximately a Nash equilibrium in the underlying noncooperative game, and vice versa. This result suggests that the difference between the two models becomes less significant when the number of players is large.