Baudouin Standaert

Reduction in pediatric rotavirus-related hospitalizations after universal rotavirus vaccination in Belgium.

Background: This study investigated the effect of pediatric vaccination against rotavirus on the number of rotavirus-related hospitalizations of children in Belgium. Methods: This retrospective database study was conducted at 12 pediatric hospitals in Belgium (546 pediatric beds, 30.6% of Belgian total). Children ≤5 years attending hospital for any reason were eligible if they had a rotavirus stool test at one of the study centers. The number of rotavirus-positive stool tests and hospitalizations for acute gastroenteritis (AGE) were compared for prevaccination (June 2004–May 2006) and postvaccination (June 2007–May 2009) study periods. Results: The number of rotavirus-positive stool tests in children who were ≤5 years of age decreased from an average of 881 in the prevaccination period to 368 in the first year postvaccination period and 199 in the second. In children 2 to 24 months of age, the percentage reductions were 65% (95% confidence interval [CI]: 62%, 69%) and 80% (95% CI: 77%, 83%) in the first and second years after vaccination, respectively, compared with prevaccination. In children <2 months, the reductions were 50% (95% CI: 36%, 64%) and 64% (95% CI: 49%, 76%), respectively, and in children >24 months the corresponding values were 20% (95% CI: 14%, 28%) and 64% (95% CI: 56%, 72%). The number of AGE-driven hospital admissions and hospitalization days for AGE declined by 33% and 36%, respectively, from prevaccination to the second year postvaccination in children ≤2 years of age. Conclusions: Pediatric rotavirus vaccination in Belgium significantly reduced rotavirus-related hospitalizations in the first and second years after introduction.

The cost-utility of rotavirus vaccination with Rotarix™ (RIX4414) in the Netherlands

The objective of this study was to estimate the cost-utility of mass vaccination of 0-4-year-old children with Rotarix in the Netherlands. We used a Markov process with Dutch data on incidence, resource use and costs (GP, hospitalisation, productivity loss and household costs) to compare vaccination to conventional treatment from a societal perspective. Utility loss due to rotavirus-induced diarrhoea was measured using EQ5D, with GPs and paediatricians serving as proxies to fill out the questions. As the costs of a vaccination course ranged from 90 euro to 100 euro per child, the cost-utility ratio varied from 21,900 euro to 35,076 euro per QALY gained. Based on the current study, it is clear that mass vaccination with Rotarix against rotavirus gastroenteritis can be attractive, from an economic and a health care perspective.

Cost-effectiveness of vaccination against cervical cancer: A multi-regional analysis assessing the impact of vaccine characteristics and alternative vaccination scenarios

Mathematical models provide valuable insights into the public health and economic impact of cervical cancer vaccination programmes. An in-depth economic analysis should explore the effects of different vaccine-related factors and vaccination scenarios (independent of screening practices) on health benefits and costs. In this analysis, a Markov cohort model was used to explore the impact of vaccine characteristics (e.g. cross-type protection and waning of immunity) and different vaccination scenarios (e.g. age at vaccination and multiple cohort strategies) on the cost-effectiveness results of cervical cancer vaccination programmes. The analysis was applied across different regions in the world (Chile, Finland, Ireland, Poland and Taiwan) to describe the influence of location-specific conditions. The results indicate that in all the different settings cervical cancer vaccination becomes more cost-effective with broader and sustained vaccine protection, with vaccination at younger ages, and with the inclusion of several cohorts. When other factors were varied, the cost-effectiveness of vaccination was most negatively impacted by increasing the discount rate applied to costs and health effects.

Cost-effectiveness analysis of a cervical cancer vaccine in five Latin American countries

Implementation of cervical cancer (CC) vaccination in Latin America is expected to reduce the high CC burden in those countries. But the efficiency of such vaccination programs in the region still remains unknown. This study assesses the cost-effectiveness and cost-utility of introducing vaccination into the current CC disease management of five Latin American countries (Argentina, Brazil, Chile, Mexico, and Peru). The modelling results indicate that universal mass vaccination is cost-effective in the current health care setting of each country (<3x gross domestic product per capita, per country) with a substantial number of CC cases and deaths avoided in addition to an increase of quality-adjusted life years. This study will help guide the design of future clinical programmes and health-related policies. It will assist early and effective decision-making processes related to vaccine implementation in Latin America.

Comparison of detailed and succinct cohort modelling approaches in a multi-regional evaluation of cervical cancer vaccination

Mathematical models have been used extensively in the evaluation of chronic diseases and in exploring the health economics of vaccination. In this study, we examine the value of having two different cohort models based on similar assumptions, one comprehensive and one simplified, which can be used to evaluate the impact of cervical cancer vaccination. To compare models, we ran cost-effectiveness analyses in four geographical regions (Italy, the UK, Taiwan and Canada). We show that the models produce comparable results and therefore can be used independently. However, as they require different complexities of data inputs, they are more suited to different circumstances depending on the level of data inputs available or the complexity of the research question asked.

Cost-effectiveness analysis of vaccination against rotavirus with RIX4414 in France

BackgroundIt is estimated that annually 300 000 cases of rotavirus-induced gastroenteritis (RVGE) occur in children aged up to 5 years in France. A two-dose vaccine against rotavirus infection (RIX4414; Rotarix™, GlaxoSmithKline), has been shown to be highly effective against severe RVGE.ObjectiveThis study evaluated the cost effectiveness of general vaccination against rotavirus using RIX4414 in France.MethodsA Markov model simulated RVGE events and the associated outcomes and costs relating to general vaccination of infants against rotavirus infection using RIX4414 (Rotarix™) in a birth cohort of children aged up to 5 years in France with a combined adjustment for age distribution with the seasonality of the infection. Costs and outcomes were estimated from a limited societal perspective, including direct medical costs paid out of pocket or by third-party payers, as well as the proportion of direct medical costs reimbursed by the health authorities. Indirect costs were not included in the base-case analysis. The primary outcome measure was the incremental cost per QALY.ResultsVaccination with RIX4414 incurred an incremental cost of €44 583 per QALY at a public price of €57 per vaccine dose. Univariate sensitivity analyses showed that the parameters with the largest influence on the results were the transition probabilities of severe diarrhoea, seeking medical advice and emergency visits, utility scores of diarrhoea (mild) in children and infants, and the discount rate for benefits. Probabilistic multivariate sensitivity analysis confirmed these results. The acceptability curve indicated that 94% of the results were under an informal threshold of €50 000 per QALY. Comparing our results with those of a recently published study using pooled data for two rotavirus vaccine products in France, the main differences are explained by differences in model structure and in data input values. They include a different age distribution of the infection, shorter duration of the at-risk period (3 years instead of 5 years), different vaccine efficacy, different unit cost data, different disease duration, and different disutility values for the health states in the model. There is a need for agreed standards to improve comparability of results from different studies.ConclusionsThe results demonstrate that a generalized vaccination strategy with RIX4414 would be cost effective in France from a limited societal perspective, depending on the baseline assumptions for disease progression and on utility scores selected.

Comparative review of three cost-effectiveness models for rotavirus vaccines in national immunization programs; a generic approach applied to various regions in the world

BackgroundThis study aims to critically review available cost-effectiveness models for rotavirus vaccination, compare their designs using a standardized approach and compare similarities and differences in cost-effectiveness outcomes using a uniform set of input parameters.MethodsWe identified various models used to estimate the cost-effectiveness of rotavirus vaccination. From these, results using a standardized dataset for four regions in the world could be obtained for three specific applications.ResultsDespite differences in the approaches and individual constituting elements including costs, QALYs Quality Adjusted Life Years and deaths, cost-effectiveness results of the models were quite similar. Differences between the models on the individual components of cost-effectiveness could be related to some specific features of the respective models. Sensitivity analysis revealed that cost-effectiveness of rotavirus vaccination is highly sensitive to vaccine prices, rotavirus-associated mortality and discount rates, in particular that for QALYs.ConclusionsThe comparative approach followed here is helpful in understanding the various models selected and will thus benefit (low-income) countries in designing their own cost-effectiveness analyses using new or adapted existing models. Potential users of the models in low and middle income countries need to consider results from existing studies and reviews. There will be a need for contextualization including the use of country specific data inputs. However, given that the underlying biological and epidemiological mechanisms do not change between countries, users are likely to be able to adapt existing model designs rather than developing completely new approaches. Also, the communication established between the individual researchers involved in the three models is helpful in the further development of these individual models. Therefore, we recommend that this kind of comparative study be extended to other areas of vaccination and even other infectious disease interventions.

Estimating utility scores in young children with acute rotavirus gastroenteritis in the UK

Abstract Objective: To estimate utility scores for different severities of acute rotavirus gastroenteritis in children aged <5 years in the UK. Methods: UK general practitioners (n=25) and paediatricians (n=25) rated four different health state descriptions of acute rotavirus gastroenteritis using the EuroQol (EQ-5D) questionnaire for children aged <18 months and 18 months to 5 years. EQ-5D scores were modified to account for limited self-care and mobility, and converted into utility values using the standard algorithm using UK data. Results: General practitioners rated the mean utility for primary care cases at 0.781 (standard deviation (sd) 0.263) and 0.688 (sd 0.345) for the younger and older age groups, respectively. For hospitalised cases the corresponding scores were 0.425 (sd 0.243) and 0.200 (sd 0.386). Paediatricians rated the mean utility for hospitalised severe cases at 0.595 (sd 0.171) and 0.634 (sd 0.217) in the younger and older groups, respectively, and for hospitalised very severe cases at 0.256 (sd 0.251) and 0.077 (sd 0.340), respectively. In all cases, the utility differences between the health states were statistically significant (p<0.0001). Conclusions: Acute rotavirus gastroenteritis substantially impairs quality of life in children aged <5 years as rated by health professionals. This study provides useful quantitative utility estimates for economic evaluations.

Selecting a Mix of Prevention Strategies against Cervical Cancer for Maximum Efficiency with an Optimization Program

AbstractBackground: Screening and vaccination against human papillomavirus (HPV) can protect against cervical cancer. Neither alone can provide 100% protection. Consequently it raises the important question about the most efficient combination of screening at specified time intervals and vaccination to prevent cervical cancer. Objective: Our objective was to identify the mix of cervical cancer prevention strategies (screening and/or vaccination against HPV) that achieves maximum reduction in cancer cases within a fixed budget. Methods: We assessed the optimal mix of strategies for the prevention of cervical cancer using an optimization program. The evaluation used two models. One was a Markov cohort model used as the evaluation model to estimate the costs and outcomes of 52 different prevention strategies. The other was an optimization model in which the results of each prevention strategy of the previous model were entered as input data. The latter model determined the combination of the different prevention options to minimize cervical cancer under budget, screening coverage and vaccination coverage constraints.We applied the model in two countries with different healthcare organizations, epidemiology, screening practices, resource settings and treatment costs: the UK and Brazil. 100 000 women aged 12 years and above across the whole population over a 1-year period at steady state were included.The intervention was papanicolaou (Pap) smear screening programmes and/or vaccination against HPV with the bivalent HPV 16/18 vaccine (Cervarix® [Cervarix is a registered trademark of the GlaxoSmithKline group of companies]). The main outcome measures were optimal distribution of the population between different interventions (screening, vaccination, screening plus vaccination and no screening or vaccination) with the resulting number of cervical cancer and associated costs. Results: In the base-case analysis (= same budget as today), the optimal prevention strategy would be, after introducing vaccination with a coverage rate of 80% in girls aged 12 years and retaining screening coverage at pre-vaccination levels (65% in the UK, 50% in Brazil), to increase the screening interval to 6 years (from 3) in the UK and to 5 years (from 3) in Brazil. This would result in a reduction of cervical cancer by 41% in the UK and by 54% in Brazil from pre-vaccination levels with no budget increase. Sensitivity analysis shows that vaccination alone at 80% coverage with no screening would achieve a cervical cancer reduction rate of 20% in the UK and 43% in Brazil compared with the pre-vaccination situation with a budget reduction of 30% and 14%, respectively. In both countries, the sharp reduction in cervical cancer is seen when the vaccine coverage rate exceeds the maximum screening coverage rate, or when screening coverage rate exceeds the maximum vaccine coverage rate, while maintaining the budget. As with any model, there are limitations to the value of predictions depending upon the assumptions made in each model. Conclusions: Spending the same budget that was used for screening and treatment of cervical cancer in the pre-vaccination era, results of the optimization program show that it would be possible to substantially reduce the number of cases by implementing an optimal combination of HPV vaccination (80% coverage) and screening at pre-vaccination coverage (65% UK, 50% Brazil) while extending the screening interval to every 6 years in the UK and 5 years in Brazil.

Impact of rotavirus vaccination on hospitalisations in Belgium: comparing model predictions with observed data.

Background Published economic assessments of rotavirus vaccination typically use modelling, mainly static Markov cohort models with birth cohorts followed up to the age of 5 years. Rotavirus vaccination has now been available for several years in some countries, and data have been collected to evaluate the real-world impact of vaccination on rotavirus hospitalisations. This study compared the economic impact of vaccination between model estimates and observed data on disease-specific hospitalisation reductions in a country for which both modelled and observed datasets exist (Belgium). Methods A previously published Markov cohort model estimated the impact of rotavirus vaccination on the number of rotavirus hospitalisations in children aged <5 years in Belgium using vaccine efficacy data from clinical development trials. Data on the number of rotavirus-positive gastroenteritis hospitalisations in children aged <5 years between 1 June 2004 and 31 May 2006 (pre-vaccination study period) or 1 June 2007 to 31 May 2010 (post-vaccination study period) were analysed from nine hospitals in Belgium and compared with the modelled estimates. Results The model predicted a smaller decrease in hospitalisations over time, mainly explained by two factors. First, the observed data indicated indirect vaccine protection in children too old or too young for vaccination. This herd effect is difficult to capture in static Markov cohort models and therefore was not included in the model. Second, the model included a ‘waning’ effect, i.e. reduced vaccine effectiveness over time. The observed data suggested this waning effect did not occur during that period, and so the model systematically underestimated vaccine effectiveness during the first 4 years after vaccine implementation. Conclusions Model predictions underestimated the direct medical economic value of rotavirus vaccination during the first 4 years of vaccination by approximately 10% when assessing hospitalisation rates as compared with observed data in Belgium.