Economic evaluation of vaccines:Considerations on evidence, discounting, models and futures challenges

OBJECTIVES: During the last decade, with the arrival of new innovative vaccines, there was a huge increase in the number of papers on economic evaluation of vaccination programmes. Our study had a 3-fold objective: 1) Appraise available methodological papers dealing with specificities of vaccines in term of health economics; 2) Illustrate the impact of each issue in term of decision-making process with concrete examples; and 3) Identify futures challenges. METHODS: A comprehensive literature search was conducted to identify methodological papers dealing with specificities of economic evaluations of vaccines. Each issue was illustrated with concrete examples of cost-effectiveness analyses recently performed for HPV vaccines, or pneumococcal diseases. RESULTS: Except guidelines issued in 2008 by the WHO and a few general papers, most of methodological papers focused on modelling techniques and showed a trend in using more and more sophisticated methods (e.g. calibration). Several papers highlighted the need for having strong dynamic transmission models of infectious diseases to evaluate appropriately the cost-effectiveness of vaccination programmes. Other papers focused on the issue of discounting, and showed the extreme impact of discounting for some vaccines given this long-term assessment, possibly warranting an alternative method of discounting for vaccines. Fewer papers highlighted the different type of clinical evidence compared with curative pharmaceutical drugs, in particular the need to model immunological responses into clinical endpoints of disease and short-term efficacy into long-term effectiveness. Although there is an increasing level of expertise in the field, other important issues such as the choice of realistic assumptions (coverage rates or vaccine prices) and the inclusion of externalities (i.e. changes in the epidemiology of the infection) are not well analysed. CONCLUSIONS: It is important for decision makers to keep in mind the above vaccine specificities when they assess the cost-effectiveness of new vaccination programmes in order to provide relevant conclusions

Additive energy forward curves in a Heath-Jarrow-Morton framework

One of the peculiarities of power and gas markets is the delivery mechanism of forward contracts. The seller of a futures contract commits to deliver, say, power, over a certain period, while the classical forward is a financial agreement settled on a maturity date. Our purpose is to design a Heath-Jarrow-Morton framework for an additive, mean-reverting, multicommodity market consisting of forward contracts of any delivery period. The main assumption is that forward prices can be represented as affine functions of a universal source of randomness. This allows us to completely characterize the models which prevent arbitrage opportunities: this boils down to finding a density between a risk-neutral measure $\mathbb{Q}$, such that the prices of traded assets like forward contracts are true $\mathbb{Q}$-martingales, and the real world probability measure $\mathbb{P}$, under which forward prices are mean-reverting. The Girsanov kernel for such a transformation turns out to be stochastic and unbounded in the diffusion part, while in the jump part the Girsanov kernel must be deterministic and bounded: thus, in this respect, we prove two results on the martingale property of stochastic exponentials. The first allows to validate measure changes made of two components: an Esscher-type density and a Girsanov transform with stochastic and unbounded kernel. The second uses a different approach and works for the case of continuous density. We apply this framework to two models: a generalized Lucia-Schwartz model and a cross-commodity cointegrated market.Comment: 28 page

Cost-effectiveness of high dose versus adjuvanted trivalent influenza vaccines in England and Wales

Aims: High dose trivalent influenza vaccine (HD TIV) and adjuvant TIV (aTIV) have been developed specifically for adults aged 65 and older (65+) who are at high risk of life-threatening complications. However, there is a scarcity of evidence comparing the clinical and cost-effectiveness of HD TIV and aTIV. The aim of this study was to determine the cost-effectiveness of HD TIV versus aTIV in the England and Wales 65+ population. Methods: A cost-utility analysis was conducted using a decision tree with two influenza related outcomes: Laboratory confirmed cases that could result in GP consultation, and hospitalizations that may result in premature mortality. Due to a lack of comparative evidence, the effectiveness of HD TIV versus aTIV was calculated indirectly, based on relative effectiveness estimates for each vaccine versus a common comparator, standard dose (SD) TIV. The primary analysis included hospitalizations explicitly due to influenza/pneumonia. Cost-effectiveness was established for three scenarios applying differing relative effectiveness estimates for aTIV versus SD TIV. Uncertainty was analysed in one-way deterministic sensitivity analyses. A secondary analysis included hospitalizations due to any respiratory illness. Results: The minimum population impact of vaccination with HD TIV rather than aTIV was 13,092 fewer influenza cases, 1,109 fewer influenza related deaths, 4,673 fewer hospitalizations, and 3,245 fewer GP appointments. HD TIV was cost-effective versus aTIV for all three effectiveness scenarios, with incremental cost-effectiveness ratios (ICER) equal to £1,932, £4,181, and £8,767 per quality adjusted life year. Results were consistent across the secondary analysis and deterministic sensitivity analyses. Limitations: The analysis was limited by a lack of robust and consistent effectiveness data for aTIV. Conclusion: HD TIV is cost-effective versus aTIV in people aged 65+ in England and Wales. Use of HD TIV over aTIV could increase clinical benefits and reduce the public health and economic burden of influenza

Epidemiology and costs of cervical cancer screening and cervical dysplasia in Italy

<p>Abstract</p> <p>Background</p> <p>We estimated the number of women undergoing cervical cancer screening annually in Italy, the rates of cervical abnormalities detected, and the costs of screening and management of abnormalities.</p> <p>Methods</p> <p>The annual number of screened women was estimated from National Health Interview data. Data from the Italian Group for Cervical Cancer Screening were used to estimate the number of positive, negative and unsatisfactory Pap smears. The incidence of CIN (cervical intra-epithelial neoplasia) was estimated from the Emilia Romagna Cancer Registry. Patterns of follow-up and treatment costs were estimated using a typical disease management approach based on national guidelines and data from the Italian Group for Cervical Cancer Screening. Treatment unit costs were obtained from Italian National Health Service and Hospital Information System of the Lazio Region.</p> <p>Results</p> <p>An estimated 6.4 million women aged 25–69 years undergo screening annually in Italy (1.2 million and 5.2 million through organized and opportunistic screening programs, respectively). Approximately 2.4% of tests have positive findings. There are approximately 21,000 cases of CIN1 and 7,000–17,000 cases of CIN2/3. Estimated costs to the healthcare service amount to €158.5 million for screening and €22.9 million for the management of cervical abnormalities.</p> <p>Conclusion</p> <p>Although some cervical abnormalities might have been underestimated, the total annual cost of cervical cancer prevention in Italy is approximately €181.5 million, of which 87% is attributable to screening.</p

ORCHIDEE-PEAT (revision 4596), a model for northern peatland CO2, water, and energy fluxes on daily to annual scales

Peatlands store substantial amounts of carbon and are vulnerable to climate change. We present a modified version of the Organising Carbon and Hydrology In Dynamic Ecosystems (ORCHIDEE) land surface model for simulating the hydrology, surface energy, and CO2 fluxes of peatlands on daily to annual timescales. The model includes a separate soil tile in each 0.5 degrees grid cell, defined from a global peatland map and identified with peat-specific soil hydraulic properties. Runoff from non-peat vegetation within a grid cell containing a fraction of peat is routed to this peat soil tile, which maintains shallow water tables. The water table position separates oxic from anoxic decomposition. The model was evaluated against eddy-covariance (EC) observations from 30 northern peatland sites, with the maximum rate of carboxylation (V-cmax) being optimized at each site. Regarding short-term day-to-day variations, the model performance was good for gross primary production (GPP) (r(2) = 0.76; Nash-Sutcliffe modeling efficiency, MEF = 0.76) and ecosystem respiration (ER, r(2) = 0.78, MEF = 0.75), with lesser accuracy for latent heat fluxes (LE, r(2) = 0.42, MEF = 0.14) and and net ecosystem CO2 exchange (NEE, r(2) = 0.38, MEF = 0.26). Seasonal variations in GPP, ER, NEE, and energy fluxes on monthly scales showed moderate to high r(2) values (0.57-0.86). For spatial across-site gradients of annual mean GPP, ER, NEE, and LE, r(2) values of 0.93, 0.89, 0.27, and 0.71 were achieved, respectively. Water table (WT) variation was not well predicted (r(2) <0.1), likely due to the uncertain water input to the peat from surrounding areas. However, the poor performance of WT simulation did not greatly affect predictions of ER and NEE. We found a significant relationship between optimized V-cmax and latitude (temperature), which better reflects the spatial gradients of annual NEE than using an average V-cmax value.Peer reviewe

Burden of paediatric Rotavirus Gastroenteritis (RVGE) and potential benefits of a universal Rotavirus vaccination programme with a pentavalent vaccine in Spain

<p>Abstract</p> <p>Background</p> <p>Rotavirus is the most common cause of gastroenteritis in young children worldwide. The aim of the study was to assess the health outcomes and the economic impact of a universal rotavirus vaccination programme with RotaTeq, the pentavalent rotavirus vaccine, versus no vaccination programme in Spain.</p> <p>Methods</p> <p>A birth cohort was followed up to the age of 5 using a cohort model. Epidemiological parameters were taken from the REVEAL study (a prospective epidemiological study conducted in Spain, 2004-2005) and from the literature. Direct and indirect costs were assessed from the national healthcare payer and societal perspectives by combining health care resource utilisation collected in REVEAL study and unit costs from official sources. RotaTeq per protocol efficacy data was taken from a large worldwide rotavirus clinical trial (70,000 children). Health outcomes included home care cases, General Practioner (GP)/Paediatrician, emergency department visits, hospitalisations and nosocomial infections.</p> <p>Results</p> <p>The model estimates that the introduction of a universal rotavirus vaccination programme with RotaTeq (90% coverage rate) would reduce the rotavirus gastroenteritis (RVGE) burden by 75% in Spain; 53,692 home care cases, 35,187 GP/Paediatrician visits, 34,287 emergency department visits, 10,987 hospitalisations and 2,053 nosocomial infections would be avoided. The introduction of RotaTeq would avoid about 76% of RVGE-related costs from both perspectives: €22 million from the national health system perspective and €38 million from the societal perspective.</p> <p>Conclusions</p> <p>A rotavirus vaccination programme with RotaTeq would reduce significantly the important medical and economic burden of RVGE in Spain.</p