Integrating Alternative Social Value Judgments Into Cost-Effectiveness Analysis of Vaccines: An Application to Varicella-Zoster Virus Vaccination.

OBJECTIVES: Cost-effectiveness analyses (CEA) are based on the value judgment that health outcomes (eg, quantified in quality-adjusted life-years; QALYs) are all equally valuable irrespective of their context. Whereas most published CEAs perform extensive sensitivity analysis on various parameters and assumptions, only rarely is the influence of the QALY-equivalence assumption on cost-effectiveness results investigated. We illustrate how the integration of alternative social value judgments in CEA can be a useful form of sensitivity analysis. METHODS: Because varicella-zoster virus (VZV) vaccination affects 2 distinct diseases (varicella zoster and herpes zoster) and likely redistributes infections across different age groups, the program has an important equity dimension. We used a cost-effectiveness model and disentangled the share of direct protection and herd immunity within the total projected QALYs resulting from a 50-year childhood VZV program in the UK. We use the UK population's preferences for QALYs in the vaccine context to revalue QALYs accordingly. RESULTS: Revaluing different types of QALYs for different age groups in line with public preferences leads to a 98% change in the projected net impact of the program. The QALYs gained among children through direct varicella protection become more important, whereas the QALYs lost indirectly through zoster in adults diminish in value. Weighting of vaccine-related side effects made a large difference. CONCLUSIONS: Our study shows that a sensitivity analysis in which alternative social value judgments about the value of health outcomes are integrated into CEA of vaccines is relatively straightforward and provides important additional information for decision makers to interpret cost-effectiveness results.

The theoretical impact and cost-effectiveness of vaccines that protect against sexually transmitted infections and disease.

Sexually transmitted diseases, a source of widespread morbidity and sometimes mortality, are caused by a diverse group of infections with a common route of transmission. Existing vaccines against hepatitis B virus (HBV) and human papilloma virus 16, 18, 6 and 11 are highly efficacious and cost effective. In reviewing the potential role for other vaccines against sexually transmitted infections (STIs) a series of questions needs to be addressed about the burden of disease, the potential characteristics of a new vaccine, and the impact of other interventions. These questions can be viewed in the light of the population dynamics of sexually transmitted infections as a group and how a vaccine can impact these dynamics. Mathematical models show the potential for substantial impact, especially if vaccines are widely used. To better make the case for sexually transmitted infection vaccines we need better data and analyses of the burden of disease, especially severe disease. However, cost effectiveness analyses using a wide range of assumptions show that STI vaccines would be cost effective and their development a worthwhile investment.

Estimating the cost-effectiveness of vaccination against herpes zoster in England and Wales.

A live-attenuated vaccine against herpes zoster (HZ) has been approved for use, on the basis of a large-scale clinical trial that suggests that the vaccine is safe and efficacious. This study uses a Markov cohort model to estimate whether routine vaccination of the elderly (60+) would be cost-effective, when compared with other uses of health care resources. Vaccine efficacy parameters are estimated by fitting a model to clinical trial data. Estimates of QALY losses due to acute HZ and post-herpetic neuralgia were derived by fitting models to data on the duration of pain by severity and the QoL detriment associated with different severity categories, as reported in a number of different studies. Other parameters (such as cost and incidence estimates) were based on the literature, or UK data sources. The results suggest that vaccination of 65 year olds is likely to be cost-effective (base-case ICER=pound20,400 per QALY gained). If the vaccine does offer additional protection against either the severity of disease or the likelihood of developing PHN (as suggested by the clinical trial), then vaccination of all elderly age groups is highly likely to be deemed cost-effective. Vaccination at either 65 or 70 years (depending on assumptions of the vaccine action) is most cost-effective. Including a booster dose at a later age is unlikely to be cost-effective.

Cost-effectiveness of a vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.

BACKGROUND: The Shingles Prevention Study showed that a varicella-zoster virus (VZV) vaccine administered to adults 60 years of age or older reduced the incidence of herpes zoster from 11.12 to 5.42 cases per 1000 person-years. Median follow-up was 3.1 years, and relative risk reduction was 51.3% (95% CI, 44.2% to 57.6%). OBJECTIVE: To assess the extent to which clinical and cost variables influence the cost-effectiveness of VZV vaccination for preventing herpes zoster in immunocompetent older adults. DESIGN: Decision theoretical model. DATA SOURCES: English-language data published to March 2006 identified from MEDLINE on herpes zoster rates, vaccine effectiveness, quality of life, medical resource use, and unit costs. TARGET POPULATION: Immunocompetent adults 60 years of age or older with a history of VZV infection. TIME HORIZON: Lifetime. PERSPECTIVE: U.S. societal. INTERVENTIONS: Varicella-zoster virus vaccination versus no vaccination. OUTCOME MEASURES: Incremental quality-adjusted survival and cost per quality-adjusted life-year (QALY) gained. RESULTS OF BASE-CASE ANALYSIS: By reducing incidence and severity of herpes zoster, vaccination can increase quality-adjusted survival by 0.6 day compared with no vaccination. One scenario in which vaccination costs less than 100,000 dollars per QALY gained is when 1) the unit cost of vaccination is less than 200 dollars, 2) the age at vaccination is less than 70 years, and 3) the duration of vaccine efficacy is more than 30 years. RESULTS OF SENSITIVITY ANALYSIS: Vaccination would be more cost-effective in "younger" older adults (age 60 to 64 years) than in "older" older adults (age > or =80 years). Longer life expectancy and a higher level of vaccine efficacy offset a lower risk for herpes zoster in the younger group. Other factors influencing cost-effectiveness include quality-of-life adjustments for acute zoster, unit cost of the vaccine, risk for herpes zoster, and duration of vaccine efficacy. LIMITATIONS: The effectiveness of VZV vaccination remains uncertain beyond the median 3.1-year duration of follow-up in the Shingles Prevention Study. CONCLUSIONS: Varicella-zoster virus vaccination to prevent herpes zoster in older adults would increase QALYs compared with no vaccination. Resolution of uncertainties about the average quality-of-life effects of acute zoster and the duration of vaccine efficacy is needed to better determine the cost-effectiveness of zoster vaccination in older adults.

Pro and contra IBR-eradication.

Bovine herpesvirus type 1 (BoHV-1) is the causative agent of respiratory and genital tract infections such as infectious rhinotracheitis (IBR), infectious pustular vulvovaginitis (IPV, balanoposthitis (IBP), and abortion. Despite of a pronounced immune response, the virus is never eliminated from an infected host but establishes life-long latency and may be reactivated at intervals. Europe has a long history of fighting against BoHV-1 infections, yet, only a small number of countries has achieved IBR-eradication. Therefore, it seemed appropriate to review the reasoning pro and contra such a task. Clearly, the goal can indeed be achieved as has been demonstrated by a number of European countries. However, detection and stamping out of seemingly healthy virus carriers is inevitable in the process. Unfortunately, the use of vaccines is only of temporary and limited value. Therefore, there are numerous considerations to be put forward against such plans, including the high costs, the great risks, and the unsatisfactory quality of tools. If either control or eradication of IBR is nonetheless a goal, then better vaccines are needed as well as better companion tests. Moreover, better tools for the characterization of viral isolates are required. Collaborative actions to gather viral strains from as many countries as possible for inclusion into a newly created clustering library would be most advantageous.

Vaccination to prevent varicella and shingles.

Vaccination of healthy children against varicella using the live attenuated Oka vaccine has been available in Japan and south Korea for several years. In 1996, a programme of universal vaccination of children to prevent varicella was introduced in the USA and other countries, including Canada, Germany, and Sweden, have licensed the vaccine for use in healthy children. This article reviews the origin of the Oka vaccine and the evidence for vaccine safety and efficacy in children and adults. Universal vaccination of children and targeted vaccination of groups at risk of severe varicella are discussed. The possible use of the Oka vaccine to prevent zoster is reviewed, and initiatives to develop new varicella zoster virus vaccines are outlined.

The epidemiology of herpes zoster and potential cost-effectiveness of vaccination in England and Wales.

The epidemiology of herpes zoster and post-herpetic neuralgia (PHN) was quantified from a variety of data sources and the potential cost-effectiveness of vaccination assessed. The annual incidence and severity of zoster increases sharply with age, as measured by physician consultation and hospitalisation rates, average length of stay, average proportion of cases developing PHN and the age-specific case-fatality ratio. Combining these data with information on health related quality of life results in an estimated loss of 20000 quality adjusted life years (QALYs) annually in England and Wales from herpes zoster (17400 due to PHN). The current cost of treating herpes zoster associated disease is estimated to be 47.6m pounds annually. Since both the health and economic burden are high, vaccination of the elderly is expected to be cost-effective under most scenarios, the attractiveness of immunisation increasing with age due to the increased burden of disease in the very elderly.