Mark H. Rozenbaum

Pharmacoeconomic evaluations of pharmacogenetic and genomic screening programmes : A systematic review on content and adherence to guidelines

The fields of pharmacogenetics and pharmacogenomics have become important practical tools to progress goals in medical and pharmaceutical research and development. As more screening tests are being developed, with some already used in clinical practice, consideration of cost-effectiveness implications is important. A systematic review was performed on the content of and adherence to pharmacoeconomic guidelines of recent pharmacoeconomic analyses performed in the field of pharmacogenetics and pharmacogenomics.Economic analyses of screening strategies for genetic variations, which were evidence-based and assumed to be associated with drug efficacy or safety, were included in the review. The 20 papers included cover a variety of healthcare issues, including screening tests on several cytochrome P450 (CYP) enzyme genes, thiopurine S-methyltransferase (TMPT) and angiotensin-converting enzyme (ACE) insertion deletion (ACE I/D) polymorphisms.Most economic analyses reported that genetic screening was cost effective and often even clearly dominated existing non-screening strategies. However, we found a lack of standardization regarding aspects such as the perspective of the analysis, factors included in the sensitivity analysis and the applied discount rates. In particular, an important limitation of several studies related to the failure to provide a sufficient evidence-based rationale for an association between genotype and phenotype.Future economic analyses should be conducted utilizing correct methods, with adherence to guidelines and including extensive sensitivity analyses. Most importantly, genetic screening strategies should be based on good evidence-based rationales. For these goals, we provide a list of recommendations for good pharmacoeconomic practice deemed useful in the fields of pharmacogenetics and pharmacogenomics, regardless of country and origin of the economic analysis.

Vaccination of risk groups in England using the 13 valent pneumococcal conjugate vaccine: economic analysis

Objective To estimate the cost effectiveness of vaccinating people with high risk conditions against invasive pneumococcal disease using the 13 valent pneumococcal conjugate vaccine. Design Economic evaluation using a cohort model from the perspective of healthcare providers. Setting England. Participants People aged 2 years and older at increased risk of invasive pneumococcal disease due to chronic kidney disease; splenic dysfunction; HIV infection; a compromised immune system; chronic heart, liver, or respiratory disease; or diabetes. Main outcome measures Costs, gains in life years and quality adjusted life years (QALYs), and incremental cost effectiveness ratios. Results Increasing indirect protection resulting from the vaccination programme of infants using the 13 valent pneumococcal conjugate vaccine means that the burden of disease preventable by targeting high risk groups will diminish in time. Under base case assumptions—that is, no overall impact on non bacteraemic pneumonia in high risk groups and assuming the high risk vaccination programme would be launched two to three years after the infant programme—the incremental cost effectiveness ratio was estimated to be more than £30 000 (€37 216;

Results of a cohort model analysis of the cost-effectiveness of routine immunization with 13-valent pneumococcal conjugate vaccine of those aged ≥65 years in the Netherlands

48 210) per QALY gained for most risk groups. If, however, the vaccine does not offer protection against non-bacteraemic pneumococcal pneumonia or the vaccine was introduced concomitantly with the infant 13 valent pneumococcal conjugate vaccination programme then vaccinating high risk people would (more) likely be cost effective. Sensitivity analyses showed that the cost effectiveness was particularly sensitive to assumed herd benefits and vaccine efficacy estimates. Conclusion Under base case assumptions it is unlikely that a pneumococcal vaccination programme aimed at risk groups could be considered cost effective. Uncertainty could be substantially reduced by establishing the effectiveness of the 13 valent pneumococcal conjugate vaccine against non-bacteraemic pneumococcal pneumonia, particularly in at risk groups.

Cost-effectiveness of varicella vaccination programs : an update of the literature

BACKGROUND Community-acquired pneumonia and invasive pneumococcal disease are common among older people (ie, those aged > or =65 years). A new 13-valent pneumococcal conjugate vaccine (PCV-13) is under study in the Netherlands. OBJECTIVE The aim of this work was to model the cost-effectiveness of PCV-13 vaccination among those aged > or =65 years in the Netherlands, both in the total population and in those at increased risk for pneumonia, for various levels of efficacy (30%-90%) assumed. METHODS Our previously published cost-effectiveness model was updated to include age-specific epidemiologic data and health-care utilization and costs for a hypothetical cohort of adults aged > or =65 years in the Netherlands. This cohort was followed twice-once as unvaccinated and once as vaccinated-over a time period of 5 years, with differences between both analyses reported. Outcome measures included costs, life-years gained (LYGs), quality-adjusted life-years, and incremental cost-effectiveness ratios (ICERs). All analyses were performed from a societal perspective. RESULTS In the model, the ICER for vaccination remained below euro80,000/LYG, except when the vaccine was assumed to protect only against bacteremic pneumonia, with a relatively low effectiveness (40%) in combination with a high vaccine price (euro65), and indirect effects of serotype replacement would largely offset the direct effect of vaccination. For various assumptions, introduction of widespread PCV-13 vaccination (assuming a 60% efficacy against invasive and noninvasive disease because of vaccine serotypes, and a cost of euro50 per vaccinated person) was associated with the ICERs varying from cost-saving to euro50,676/LYG. CONCLUSIONS In this model analysis of a hypothetical cohort in the Netherlands, vaccination with PCV-13 might be considered cost-effective, both for the total population and for the high-risk population aged > or =65 years, from a societal perspective, over a 5-year time horizon. The main limitation of this study was uncertainty regarding how great a proportion of pneumonia could be attributed to pneumococcal disease.

Cost-effectiveness of adult pneumococcal conjugate vaccination in the Netherlands.

Varicella is one of the most common infectious diseases in childhood, caused by the varicella zoster virus. Although vaccines are available, there are only a few countries with an early-childhood vaccination program. Most countries mainly focus on vaccination of high-risk groups, such as susceptible healthcare workers. One of the main concerns with a routine early-childhood vaccination program is a potential (temporal) increase of the incidence of herpes zoster among elderly adults. In this review, we focus on the cost–effectiveness of varicella vaccination and on the methodology used in the health–economic studies. In particular, we focus on the perspective adopted, type of model used, the modeled effect on herpes zoster, the vaccine efficacy and price, and on the value of time lost by infection. The vast majority of studies show vaccination of high-risk groups – including susceptible adolescents – to be cost saving. Routine early-childhood vaccination programs are always cost saving if indirect costs of production losses are included, or cost effective, as long as the potential negative effects on zoster are not taken into account. We note that most studies included in the review used old vaccine prices and a single dose of the varicella vaccine, whereas multiple doses are now becoming the standard. Despite that, those aspects limit the timeliness of our review and we believe that the current work does provide useful insights in the cost–effectiveness of varicella vaccination.

The role of Streptococcus pneumoniae in community-acquired pneumonia among adults in Europe: a meta-analysis

The Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) demonstrated the efficacy of 13-valent pneumococcal conjugate vaccine (PCV13) in preventing vaccine-type community-acquired pneumonia and vaccine-type invasive pneumococcal disease in elderly subjects. We examined the cost-effectiveness of PCV13 vaccination in the Netherlands. Using a Markov-type model, incremental cost-effectiveness ratios (ICER) of PCV13 vaccination in different age- and risk-groups for pneumococcal disease were evaluated using a societal perspective. Estimates of quality-adjusted life-years (QALYs), costs, vaccine efficacy and epidemiological data were based on the CAPiTA study and other prospective studies. The base-case was PCV13 vaccination of adults aged 65–74 years compared to no vaccination, assuming no net indirect effects in base-case due to paediatric 10-valent pneumococcal conjugate vaccine use. Analyses for age- and risk-group specific vaccination strategies and for different levels of hypothetical herd effects from a paediatric PCV programme were also conducted. The ICER for base-case was €8650 per QALY (95% CI 5750–17 100). Vaccination of high-risk individuals aged 65–74 years was cost-saving and extension to medium-risk individuals aged 65–74 years yielded an ICER of €2900. Further extension to include medium- and high-risk individuals aged ≥18 years yielded an ICER of €3100. PCV13 vaccination is highly cost-effective in the Netherlands. The transferability of our results to other countries depends upon vaccination strategies already implemented in those countries. Vaccinating the elderly with 13-valent pneumococcal conjugate vaccine is highly cost-effective http://ow.ly/NVeui

Cost-effectiveness of rotavirus vaccination in the Netherlands; the results of a consensus model

The primary objective of this meta-analysis was to estimate the prevalence of adult community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae in Europe, adjusted for possible independent covariates. Two reviewers conducted a systematic literature search using PubMed on English-language articles that involved human subjects with CAP during the period from January 1990 to November 2011 across European countries. A mixed-effects meta-regression model was developed and populated with 24,410 patients obtained from 77 articles that met the inclusion criteria. The model showed that the observed prevalence of S. pneumoniae in CAP significantly varies between European regions, even after adjusting for explanatory covariates, including patient characteristics, diagnostic tests, antibiotic resistance, and health-care setting. The probability of detecting S. pneumoniae was substantially higher in studies that performed more frequently a diagnostic polymerase chain reaction assay compared to all the other diagnostic tests included. Furthermore, S. pneumoniae was more likely to be confirmed as the cause of a CAP in studies with intensive care unit patients as compared to those with hospital- or community-treated patients. This study provides estimates of the average observed prevalence of S. pneumoniae, which could be used for projecting the health and economic benefits of pneumococcal immunization.

Until Which Age Should Women Be Vaccinated Against HPV Infection? Recommendation Based on Cost-effectiveness Analyses

BackgroundEach year rotavirus gastroenteritis results in thousands of paediatric hospitalisations and primary care visits in the Netherlands. While two vaccines against rotavirus are registered, routine immunisation of infants has not yet been implemented. Existing cost-effectiveness studies showed inconsistent results for these vaccines because of lack of consensus on the impact. We aimed to investigate which factors had a major impact on cost-effectiveness and were primarily responsible for the large differences in previously estimated cost-effectiveness ratios.MethodsBased on updated data on health outcomes and cost estimates, we re-assessed the cost-effectiveness of routine paediatric rotavirus vaccination within the National Immunization Program for the Netherlands. Two consensus meetings were organised with national and international experts in the field to achieve consensus and resolve potential controversies.ResultsIt was estimated that rotavirus vaccination in the Netherlands could avert 34,214 cases of rotavirus gastroenteritis in children aged less than 5 years. Notably, 2,779 hospitalisations were averted of which 315 were extensions of existing hospital stays due to nosocomial rotavirus infection. With a threshold varying from 20K€ - 50K€ per QALY and according to the base-case scenario, the full vaccination costs per child leading to cost-effectiveness was €57.76 -€77.71. Results were sensitive to the inclusion of potential vaccine induced herd protection, QALY losses and number of deaths associated with rotavirus gastroenteritis.ConclusionsOur economic analysis indicates that inclusion of rotavirus vaccination in the Dutch National Immunization Program might be cost-effective depending on the cost of the vaccine and the impact of rotavirus gastroenteritis on childrens quality of life.

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

INTRODUCTION Cervical cancer is caused by infection with human papillomavirus (HPV). Several countries have implemented vaccination programs against HPV for teenage girls before sexual debut. However, recent clinical trials have demonstrated that vaccination of older women is highly effective as well. Accordingly, it has been suggested that these older women should also be offered vaccination. Here, the cost-effectiveness of HPV vaccination for older women was assessed. METHODS A Markov model was used to estimate age-specific health benefits and cost savings of HPV vaccination for women 12-50 years of age, in the Netherlands. Sensitivity analyses were performed to test the robustness of the outcomes. State-of-the-art health-economic methods were used, and international health-economic guidelines were followed. RESULTS HPV vaccination is highly cost-effective for girls aged 12-16 years. Remarkably, cost-effectiveness only slowly declines with increasing age of the vaccinees up to 25 years. Indeed, substantial health benefits can be obtained by vaccinating women in this age group at acceptable costs. Beyond this age, cost-effectiveness of HPV-vaccination rapidly declines. CONCLUSIONS Not only HPV vaccination of girls before sexual debut is a highly effective and cost-effective strategy for prevention of cervical cancer, but also vaccination of women until the age of 25 years is generally cost-effective.

Observed differences in invasive pneumococcal disease epidemiology after routine infant vaccination

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.