Duration Of Vaccine Efficacy Research Articles

Herpes zoster vaccine: A health economic evaluation for Switzerland

ABSTRACTHerpes zoster (HZ) or “shingles” results from a reactivation of the varicella zoster virus (VZV) acquired during primary infection (chickenpox) and surviving in the dorsal root ganglia. In about 20% of cases, a complication occurs, known as post-herpetic neuralgia (PHN). A live attenuated vaccine against VZV is available for the prevention of HZ and subsequent PHN. The present study aims to update an earlier evaluation estimating the cost-effectiveness of the HZ vaccine from a Swiss third party payer perspective. It takes into account updated vaccine prices, a different age cohort, latest clinical data and burden of illness data. A Markov model was developed to simulate the lifetime consequences of vaccinating 15% of the Swiss population aged 65–79 y. Information from sentinel data, official statistics and published literature were used. Endpoints assessed were number of HZ and PHN cases, quality-adjusted life years (QALYs), costs of hospitalizations, consultations and prescriptions. Based on a vaccine price of CHF 162, the vaccination strategy accrued additional costs of CHF 17,720,087 and gained 594 QALYs. The incremental cost-effectiveness ratio (ICER) was CHF 29,814 per QALY gained. Sensitivity analyses showed that the results were most sensitive to epidemiological inputs, utility values, discount rates, duration of vaccine efficacy, and vaccine price. Probabilistic sensitivity analyses indicated a more than 99% chance that the ICER was below 40,000 CHF per QALY. Findings were in line with existing cost-effectiveness analyses of HZ vaccination. This updated study supports the value of an HZ vaccination strategy targeting the Swiss population aged 65–79 y.

Optimizing age of cytomegalovirus screening and vaccination to avert congenital disease in the US

Cytomegalovirus (CMV) infection is the leading cause of congential cognitive deficit, visual impairment and hearing loss in the US. Clinical trials are underway to evaluate the efficacy of CMV vaccine candidates in seronegative females. The optimal age of such vaccination depends on the interplay among age-specific transmission dynamics, vaccine efficacy and vaccine waning. We developed an age-structured model of CMV transmission dynamics in the US and estimated age-specific transmission rates of CMV based on age-stratified CMV prevalence, congenital infections per birth, breastfeeding patterns and demographic data. We found that the optimal age of vaccination depended on the duration of vaccine protection. For most scenarios, the optimal age of vaccination was between 19 and 21 years of age. However, for a rapidly waning vaccine, the optimal age of vaccination can shift to infants under 1 year. This shift arises when the duration of vaccine efficacy is too brief to offer appreciable protection during the child-bearing years. In this case, it becomes more effective to achieve indirect protection by reducing transmission from infants, the transmissibility from whom was estimated to be an order of magnitude higher than other age classes. Knowledge of vaccine waning is paramount to optimizing CMV vaccination and is thus a key parameter for longitudinal clinical evaluation.

Duration of vaccine efficacy against malaria: 5th year of follow-up in children vaccinated with RTS,S/AS02 in Mozambique

A primary concern for the RTS,S malaria vaccine candidate is duration of protection. The ongoing Phase III trial reported evidence of waning efficacy within the first year following vaccination. Multiple Phase IIb trials demonstrated early waning of efficacy. The longest duration of protection for RTS,S recorded to date was in a trial of a cohort of 1605 Mozambican children age 1–4 yr at the time of immunization (C1), which showed an overall efficacy against clinical malaria of 30.5% over 43 subsequent months of surveillance. A significant reduction in parasite prevalence in RTS,S vaccinees indicated that the vaccine continued to protect at the end of this period. Although follow-up for recording incident cases of clinical malaria was stopped at 45 months, we were interested in evidence of further durability of protection, and revisited the cohort at 63 months, recording the secondary trial endpoint, prevalence of asexual Plasmodium falciparum parasitemia, in the RTS,S and comparator vaccine groups as a proxy for efficacy. As a comparator, we also visited the contemporaneous cohort of 417 children (C2), which showed waning efficacy after 6 months of follow-up. We also assessed anti-circumsporozoite antibody titers. These results were compared with those of other Phase IIb trials. Prevalence of parasitemia was not significantly lower in the RTS,S/AS02 group compared to comparator groups in C1 (57 [119%] Vs 62 [128%]; p=0.696) or C2 (30 [226%] Vs 35 [276%]; p=0.391), despite elevated antibody titers, suggesting that protection did not extend to 5 years after vaccination. This is in contrast to the earlier assessment of parasitemia in C1, where a 34% lower prevalence of parasitemia was observed in the RTS,S/AS02 group at month 45. Comparison with other Phase II trials highlights a complex relationship between efficacy, age and transmission intensity. RTS,S/AS02 provided partial protection from clinical malaria for at least 3.5 years in C1. Duration of protection may depend on environmental circumstances, such as changing malaria transmission, and special attention should be given in the Phase III trial to identifying factors that modify longevity of protection.

A Systematic Review of the Cost Effectiveness of Herpes Zoster Vaccination

The varicella zoster virus (VZV) can cause two infections: chickenpox or herpes zoster (HZ). Whereas chickenpox infections are normally mild but common among children, HZ infections are common among elderly people and can give rise to post-herpetic neuralgia (PHN), a severe and painful complication. This review aimed to summarize the literature available on the cost effectiveness of HZ vaccination and to summarize key issues for decision makers to consider when deciding on the reimbursement of HZ vaccination. We conducted a literature search of the databases PubMed and EMBASE using EndNote X4 from Thomson Reuters. The following combinations of keywords were used: 'herpes zoster vaccine' AND 'cost(-)effectiveness' or AND 'economic evaluation', 'herpes zoster vaccination' AND 'cost(-)effectiveness' or AND 'economic evaluation', 'varicella zoster vaccine' AND 'cost(-)effectiveness' or AND 'economic evaluation', and 'varicella zoster vaccination' AND 'cost(-)effectiveness' or AND 'economic evaluation'. A total of 11 studies were identified and included. Cost-effectiveness analyses of varicella zoster vaccination were excluded. The quality of the included studies ranged from 'moderate' to 'moderate to good' according to the British Medical Journal guidelines of Drummond and Jefferson and the Quality of Health Economic Studies (QHES) score of Ofman et al. Most studies evaluated the cost effectiveness of universal HZ vaccination in adults aged 50years or 60years and older. Data sources and model assumptions regarding epidemiology, utility estimates and costs varied between studies. All studies calculated costs per QALY, which allows comparing costs of interventions in different diseases. The costs per QALY gained and the incremental cost-effectiveness ratio (ICER) differed between studies depending on the age at vaccination, duration of vaccine efficacy, cost of vaccine course and economic perspective. All but one of the studies concluded that most vaccination scenarios are cost effective and the vaccination of specific subgroups such as the older age group is most cost effective. Model input parameters such as age at vaccination, vaccine costs, HZ incidence, PHN length and duration of vaccine efficacy had a great impact on the estimated cost effectiveness of HZ vaccination. To compare the results of different cost-effectiveness studies of HZ vaccination, uniform methods should be used and the most important input parameters used for the different models should be critically assessed.

Prophylactic HPV Vaccines and Prevention of Cervical Intraepithelial Neoplasia

Cervical cancer kills women of all ages. The irrefutable link to oncogenic human papillomavirus (HPV), a sexually transmitted infection, forever changed society’s attitude toward cervical cancer. The advent of HPV vaccines has brought the link of sexual practices and personal behavior to the forefront. The vaccines were aggressively marketed to parents, young girls, public health officials, physicians, and all payor sources before the scientific data defining their actual benefit could be delineated. At this early time, the HPV vaccines prevent persistent type-specific HPV infections, some abnormal Pap tests, some colposcopies, and some excisional procedures in women who are HPV-DNA negative before vaccination. Health-modeling exercises have demonstrated that duration of vaccine efficacy is the most important parameter for any long-term cancer prevention benefit. Implementation efforts have demonstrated that a three-dose series is difficult to achieve and results in a high vaccine wastage rate.

Outcomes and costs associated with PHiD-CV, a new protein D conjugate pneumococcal vaccine, in four countries

This study estimated the impact of routine vaccination of infants with a new 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) on health outcomes and costs across the entire population in Canada, Germany, Mexico, and Norway. A compartmental, static model with a 1-year time period for a steady-state population that allowed for the incorporation of direct and indirect (i.e., herd immunity and serotype replacement) vaccine effects across all age groups was used. Cases of disease prevented, deaths prevented, life-years gained, quality-adjusted life-years gained, and incremental costs in the steady-state year were calculated for PHiD-CV compared with 7-valent pneumococcal conjugate vaccine (PCV-7). A short-term analysis was also conducted to estimate the incremental difference in disease and cost outcomes for the two vaccines within the first 10 years. All costs were in 2008 local currency. In all four countries, the model estimated that PHiD-CV prevented more cases of disease, prevented more deaths, and resulted in more life-years and quality-adjusted life-years compared with PCV-7 in both the short term and the steady-state year. Assuming price parity for the vaccines, the model projected that routine vaccination with PHiD-CV resulted in lower costs compared with PCV-7 in both the short term and the steady-state year. Scenario analysis showed the incremental cost savings for PHiD-CV compared with PCV-7 in the steady-state year were sensitive to assumptions regarding duration of vaccine efficacy.

Health economic evaluation of a vaccine for the prevention of herpes zoster (shingles) and post-herpetic neuralgia in adults in Belgium

Objective:To determine the cost-effectiveness of vaccination against herpes zoster (HZ) and post-herpetic neuralgia (PHN) in individuals aged 60 years and older in Belgium.Methods:A Markov model was developed to compare the cost-effectiveness of vaccination with that of a policy of no vaccination. The model estimated the lifetime incidence and consequences of HZ and PHN using inputs derived from Belgian data, literature sources, and expert opinion. Cost-effectiveness was measured by the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life-year (QALY) gained.Results:Vaccination in individuals aged 60 years and older resulted in ICERs of €6,799 (third party payer perspective), €7,168 (healthcare perspective), and €7,137 (societal perspective). The number needed to vaccinate to prevent one case was 12 for HZ, and 35 or 36 for PHN depending on the definition used. Univariate sensitivity analyses produced ICERs of €4,959–19,052/QALY; duration of vaccine efficacy had the greatest impact on cost-effectiveness. Probabilistic sensitivity analysis showed at least a 94% probability of ICERs remaining below the unofficial €30,000 threshold.Discussion:Key strengths of the model are the combination of efficacy data from a pivotal clinical trial with country-specific epidemiological data and complete sensitivity analysis performed. Main limitations are the use of non country-specific PHN proportion and non Belgian disease-specific utilities. Results are comparable with those recently published.Conclusions:HZ vaccination in individuals aged 60 years and older would represent a cost-effective strategy in Belgium.

Adding a quadrivalent human papillomavirus vaccine to the UK cervical cancer screening programme: A cost-effectiveness analysis.

BackgroundWe assessed the cost-effectiveness of adding a quadrivalent (6/11/16/18) human papillomavirus (HPV) vaccine to the current screening programme in the UK compared to screening alone.MethodsA Markov model of the natural history of HPV infection incorporating screening and vaccination was developed. A vaccine that prevents 98% of HPV 6, 11, 16 and 18-associated disease, with a lifetime duration and 85% coverage, in conjunction with current screening was considered.ResultsVaccination with screening, compared to screening alone, was associated with an incremental cost-effectiveness ratio of £21,059 per quality adjusted life year (QALY) and £34,687 per life year saved (LYS). More than 400 cases of cervical cancer, 6700 cases of cervical intraepithelial neoplasia and 4750 cases of genital warts could be avoided per 100,000 vaccinated girls. Results were sensitive to assumptions about the need for a booster, the duration of vaccine efficacy and discount rate.ConclusionThese analyses suggest that adding a quadrivalent HPV vaccine to current screening in the UK could be a cost-effective method for further reducing the burden of cervical cancer.

Evaluation of the cost-effectiveness in the United States of a vaccine to prevent herpes zoster and postherpetic neuralgia in older adults

Context A live-attenuated varicella–zoster virus vaccine, demonstrated to reduce the incidence of herpes zoster (HZ) and postherpetic neuralgia (PHN) and the morbidity associated with incident HZ and its sequelae, has recently been approved for use in the United States (U.S.). Objective To examine the potential value of zoster vaccine for society and payers. Design, setting and population An age-specific decision analytic model was designed to estimate the lifetime costs and outcomes associated with HZ, PHN and other HZ-related complications for vaccinated and non-vaccinated cohorts aged ≥60 years. Clinical trial data, published literature and other primary studies were used to inform the model. Robustness of results to key model parameters was explored through a series of one-way, multivariate and probabilistic sensitivity analyses. Both societal and payer perspectives were considered. Main outcome measure Incremental cost per quality-adjusted life year (QALY) gained. Results For a representative cohort of 1,000,000 U.S. vaccine recipients aged ≥60 years, use of the zoster vaccine was projected to eliminate 75,548–88,928 HZ cases and over 20,000 PHN cases. Over 300,000 outpatient visits, 375,000 prescriptions, 9700 ER visits and 10,000 hospitalizations were projected to be eliminated with the vaccine translating into savings of US$ 82 million to US$ 103 million in healthcare costs associated with the diagnosis and treatment of HZ, PHN and other HZ-related complications. Cost-effectiveness ratios range from US$ 16,229 to US$ 27,609 per QALY gained, depending on the input data source and analytic perspective. Results were most sensitive to PHN costs, duration of vaccine efficacy, vaccine efficacy against PHN and HZ, QALY loss associated with pain states and complication costs. Conclusions The zoster vaccine at a price of US$ 150 is likely to be cost-effective for a cohort of immunocompetent U.S. vaccine recipients aged ≥60 years using commonly cited thresholds for judging cost-effectiveness. Conclusions are robust over plausible ranges of input parameter values and a broad range of scenarios and age cohorts.

Implementation of an HPV-Vaccination Program

Human papillomavirus (HPV) infection can lead to the development of cervical cancer, the second most common cancer-related cause of death in women in the world. The availability of HPV vaccines provides a new and exciting opportunity for cervical cancer prevention. Currently available phase II and III trial data suggest that HPV vaccines are highly effective in preventing infection with HPV-16 and -18, the two types responsible for approximately 70% of cervical cancers worldwide. In order to determine how best to successfully implement a vaccination program, there are a number of factors that need to be considered in addition to vaccine efficacy. These include the choice of a disease endpoint, the duration of vaccine efficacy, the HPV types included in the vaccine, vaccine costs, vaccine coverage, and how the availability of an effective vaccination program may affect screening for those countries that have a successful screening program in place. For settings in which screening is already in place, there will need to be a careful consideration of new approaches to screening, including screening less frequently and using new screening tests or strategies. For settings that have a high burden of cervical cancer but that have not implemented screening, additional trial and registry data that not only confirm the initial results showing high efficacy but also show significant reductions in pre-cancer, and ultimately cancer, will provide reassurance that a decision to implement an HPV vaccination program is sound.

A cost-effectiveness analysis of adding a human papillomavirus vaccine to the Australian National Cervical Cancer Screening Program

The cost-effectiveness of adding a human papillomavirus (HPV) vaccine to the Australian National Cervical Screening Program compared to screening alone was examined. A Markov model of the natural history of HPV infection that incorporates screening and vaccination was developed. A vaccine that prevents 100% of HPV 16/18-associated disease, with a lifetime duration of efficacy and 80% coverage offered through a school program to girls aged 12 years, in conjunction with current screening was compared with screening alone using cost (in Australian dollars) per life-year (LY) saved and quality-adjusted life-year (QALY) saved. Sensitivity analyses included determining the cost-effectiveness of offering a catch-up vaccination program to 14-26-year-olds and accounting for the benefits of herd immunity. Vaccination with screening compared with screening alone was associated with an incremental cost-effectiveness ratio (ICER) of $51 103 per LY and $18 735 per QALY, assuming a cost per vaccine dose of $115. Results were sensitive to assumptions about the duration of vaccine efficacy, including the need for a booster ($68 158 per LY and $24 988 per QALY) to produce lifetime immunity. Accounting for herd immunity resulted in a more attractive ICER ($36 343 per LY and $13 316 per QALY) for girls only. The cost per LY of vaccinating boys and girls was $92 052 and the cost per QALY was $33 644. The cost per LY of implementing a catch-up vaccination program ranged from $45 652 ($16 727 per QALY) for extending vaccination to 14-year-olds to $78 702 ($34 536 per QALY) for 26-year-olds. These results suggest that adding an HPV vaccine to Australia's current screening regimen is a potentially cost-effective way to reduce cervical cancer and the clinical interventions that are currently associated with its prevention via screening alone.

Cost-Effectiveness of a Vaccine To Prevent Herpes Zoster and Postherpetic Neuralgia in Older Adults

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%). 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. Decision theoretical model. 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. Immunocompetent adults 60 years of age or older with a history of VZV infection. Lifetime. U.S. societal. Varicella-zoster virus vaccination versus no vaccination. Incremental quality-adjusted survival and cost per quality-adjusted life-year (QALY) gained. 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. 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. The effectiveness of VZV vaccination remains uncertain beyond the median 3.1-year duration of follow-up in the Shingles Prevention Study. 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.

Projected clinical benefits and cost-effectiveness of a human papillomavirus 16/18 vaccine.

Human papillomavirus (HPV) vaccine may be commercially available in a few years. We explored the clinical benefits and cost-effectiveness of introducing an HPV16/18 vaccine in a population with an organized cervical cancer screening program. A computer-based model of the natural history of HPV and cervical cancer was used to project cancer incidence and mortality, life expectancy (adjusted and unadjusted for quality of life), lifetime costs, and incremental cost-effectiveness ratios (i.e., the additional cost of a strategy divided by its additional clinical benefit compared with the next most expensive strategy) associated with different cancer prevention policies, including vaccination (initiated at age 12 years), cytologic screening (initiated at 18, 21, 25, 30, or 35 years), and combined vaccination and screening strategies. We assumed that vaccination was 90% effective in reducing the risk of persistent HPV16/18 infections and evaluated alternative assumptions about vaccine efficacy, waning immunity, and risk of replacement with non-16/18 HPV types. Our model showed that the most effective strategy with an incremental cost-effectiveness ratio of less than 60 dollars-000 per quality-adjusted life year is one combining vaccination at age 12 years with triennial conventional cytologic screening beginning at age 25 years, compared with the next best strategy of vaccination and cytologic screening every 5 years beginning at age 21 years. This triennial strategy would reduce the absolute lifetime risk of cervical cancer by 94% compared with no intervention. These results were sensitive to alternative assumptions about the underlying patterns of cervical cancer screening, duration of vaccine efficacy, and natural history of HPV infection in older women. Our model predicts that a vaccine that prevents persistent HPV16/18 infection will reduce the incidence of HPV16/18-associated cervical cancer, even in a setting of cytologic screening. A program of vaccination that permits a later age of screening initiation and a less frequent screening interval is likely to be a cost-effective use of health care resources.

Potential health and economic impact of adding a human papillomavirus vaccine to screening programs.

Recently published results suggest that effective vaccines against cervical cancer-associated human papillomavirus (HPV) may become available within the next decade. To examine the potential health and economic effects of an HPV vaccine in a setting of existing screening. A Markov model was used to estimate the lifetime (age 12-85 years) costs and life expectancy of a hypothetical cohort of women screened for cervical cancer in the United States. Three strategies were compared: (1) vaccination only; (2) conventional cytological screening only; and (3) vaccination followed by screening. Two of the strategies incorporated a vaccine targeted against a defined proportion of high-risk (oncogenic) HPV types. Screening intervals of 1, 2, 3, and 5 years and starting ages for screening of 18, 22, 24, 26, and 30 years were chosen for 2 of the strategies (conventional cytological screening only and vaccination followed by screening). Incremental cost per life-year gained. Vaccination only or adding vaccination to screening conducted every 3 and 5 years was not cost-effective. However, at more frequent screening intervals, strategies combining vaccination and screening were preferred. Vaccination plus biennial screening delayed until age 24 years had the most attractive cost-effectiveness ratio (44 889 dollars) compared with screening only beginning at age 18 years and conducted every 3 years. However, the strategy of vaccination with annual screening beginning at age 18 years had the largest overall reduction in cancer incidence and mortality at a cost of 236 250 dollars per life-year gained compared with vaccination and annual screening beginning at age 22 years. The cost-effectiveness of vaccination plus delayed screening was highly sensitive to age of vaccination, duration of vaccine efficacy, and cost of vaccination. Vaccination for HPV in combination with screening can be a cost-effective health intervention, but it depends on maintaining effectiveness during the ages of peak oncogenic HPV incidence. Identifying the optimal age for vaccination should be a top research priority.