Pharmacoeconomics of influenza vaccination for healthy working adults: reviewing the available evidence

A favourable pharmacoeconomic profile has been well established for influenza vaccination in the elderly. For employers relevant benefits seem to exist for vaccinating healthy working adults to avert absenteeism and related production losses. From a pharmacoeconomic point of view it is relevant to consider whether societal benefits of vaccination for healthy working adults is worthwhile given the costs of vaccination for the community. We searched Medline and Embase using the key words influenza (vaccination) in combination with cost, cost-benefit, cost-effectiveness, efficiency, economic evaluation, health-policy and pharmacoeconomics. From this primary search, we selected 11 studies concerned with the group of healthy working adults. We reviewed these studies according to several criteria: benefit-to-cost (B/C) ratio;vaccine effectiveness, influenza incidence, number of days of work absence due to illness; and relative cost of the vaccine. Three studies on vaccinating healthy working adults found costs exceeding the benefits (B/C-ratio <1). The remaining eight pharmacoeconomic studies found a B/C-ratio of almost two or more. Cost savings are strongly related to the inclusion of indirect benefits related to averted production losses. After exclusion of indirect costs and benefits of production gains/losses, only one of the eight studies remains cost saving. Considering the available pharmacoeconomic evidence, vaccination of healthy working adults in Western countries may be an intervention with favourable cost-effectiveness and cost-saving potentials if indirect benefits of averted production losses are included. Excluding indirect benefits and costs of production losses/gains, cost-saving potentials are limited. Recent international guidelines for pharmacoeconomic research advise the inclusion of production gains and losses in the preferred societal perspective. Hence, on the basis of the available evidence, influenza vaccination of healthy working adults may be recommended from pharmacoeconomic point of view. Pharmacoeconomics do, however, present only one argument for consideration aside from ethical issues, budgetary limits and psychosocial aspects.     

Socioeconomics of influenza and influenza vaccination in Europe

Although the effectiveness of influenza vaccination is established vaccination policies and their implementation differ considerably across Europe. Historically the selective policies for influenza vaccination were based on the proven efficacy of influenza vaccine in healthy volunteers, and recognition that influenza complications and death occur mostly in elderly people with chronic medical conditions. Healthcare providers are faced with increasingly aging populations and costly new technologies and are more likely to extend immunisation policies if new initiatives are cost effective compared with accepted measures. Few studies of vaccine effectiveness focus on elderly cohorts with and without high risk conditions. Accordingly, healthcare providers in Denmark, Sweden, The Netherlands and the UK may require further data on vaccine effectiveness in elderly people without high risk conditions before reconsidering their policies. Scandinavian countries may also require data demonstrating benefits in people with diabetes. Review of recent US studies indicates that the available data on vaccine effectiveness in preventing influenza-related hospitalisation and death are applicable in Europe, but vaccine costs and cost effectiveness, and the overall economic burden of inpatient and outpatient care, need to be assessed country by country.     

Rotavirus vaccine RIX4414 (Rotarix™): a pharmacoeconomic review of its use in the prevention of rotavirus gastroenteritis in developing countries

This article provides an overview of the clinical profile of rotavirus vaccine RIX4414 (Rotarix?) in the prevention of rotavirus gastroenteritis (RVGE) in developing countries, followed by a comprehensive review of pharmacoeconomic analyses with the vaccine in low- and middle-income countries. RVGE is associated with significant morbidity and mortality among children <5 years of age in developing countries. The protective efficacy of a two-dose oral series of rotavirus vaccine RIX4414 has been demonstrated in several well designed clinical trials conducted in developing countries, and the 'real-world' effectiveness of the vaccine has also been shown in naturalistic and case-control trials after the introduction of universal vaccination programmes with RIX4414 in Latin American countries. The WHO recommends universal rotavirus vaccination programmes for all countries. Numerous modelled cost-effectiveness analyses have been conducted with rotavirus vaccine RIX4414 across a wide range of low- and middle-income countries. Although data sources and assumptions varied across studies, results of the analyses consistently showed that the introduction of the vaccine as part of a national vaccination programme would be very (or highly) cost effective compared with no rotavirus vaccination programme, according to widely used cost-effectiveness thresholds for developing countries. Vaccine price was not known at the time the analyses were conducted and had to be estimated. In sensitivity analyses, rotavirus vaccine RIX4414 generally remained cost effective at the highest of a range of possible vaccine prices considered. Despite these favourable results, decisions regarding the implementation of universal vaccination programmes with RIX4414 may also be contingent on budgetary and other factors, underscoring the importance of subsidized vaccination programmes for poor countries through the GAVI Alliance (formerly the Global Alliance for Vaccines and Immunization).     

Rotavirus vaccine RIX4414 (Rotarix™): a pharmacoeconomic review of its use in the prevention of rotavirus gastroenteritis in developed countries

The most common cause of severe diarrhoea in infants and young children is rotavirus gastroenteritis (RVGE), which is associated with significant morbidity, healthcare resource use and direct and indirect costs in industrialized nations. The monovalent rotavirus vaccine RIX4414 (Rotarix?) is administered as a two-dose oral series in infants and has demonstrated protective efficacy against RVGE in clinical trials conducted in developed countries. In addition, various naturalistic studies have demonstrated 'real-world' effectiveness after the introduction of widespread rotavirus vaccination programmes in the community setting. Numerous cost-effectiveness analyses have been conducted in developed countries in which a universal rotavirus vaccination programme using RIX4414 was compared with no universal rotavirus vaccination programme. There was a high degree of variability in base-case results across studies even when conducted in the same country, often reflecting differences in the selection of data sources or assumptions used to populate the models. In addition, results were sensitive to plausible changes in a number of key input parameters. As such, it is not possible to definitively state whether a universal rotavirus vaccination programme with RIX4414 is cost effective in developed countries, although results of some analyses in some countries suggest this is the case. In addition, international guidelines advocate universal vaccination of infants and children against rotavirus. It is also difficult to draw conclusions regarding the cost effectiveness of rotavirus vaccine RIX4414 relative to that of the pentavalent rotavirus vaccine, which is administered as a three-dose oral series. Although indirect comparisons in cost-effectiveness analyses indicate that RIX4414 provided more favourable incremental cost-effectiveness ratios when each vaccine was compared with no universal rotavirus vaccination programme, results were generally sensitive to vaccine costs. Actual tender prices of a full vaccination course for each vaccine were not known at the time of the analyses and therefore had to be estimated.     

Evaluating the impact of influenza vaccination. A North American perspective

Recent studies in the US and Canada have shown that influenza vaccination prevents approximately 30 to 50% of all pneumonia and influenza hospitalisations and deaths that occur among elderly persons during 3-month influenza outbreak periods. These population-based studies have used retrospective methods and large computerised administrative databases. In addition, earlier cost-effectiveness studies have been supplemented by recent research from prepaid health plans showing that influenza vaccination can be cost saving. The use of influenza vaccine increased in the US and Canada throughout the 1980s and early 1990s, despite different methods for providing reimbursement for vaccination. The North American experience regarding the clinical effectiveness, cost effectiveness and epidemiology of influenza vaccination may provide European scientists and health officials with useful although sometimes limited insight into their own efforts to understand and improve influenza vaccination.     

Seasonal influenza vaccination of the elderly

The elderly are at increased risk of the complications of seasonal influenza. Annual vaccination is therefore recommended. However, two systematic reviews published by the Cochrane collaboration have highlighted a number of outstanding issues. This article examines whether annual influenza vaccination of the elderly and their regular contacts is still supported by the available scientific evidence. The randomised trials included in one of the Cochrane reviews suggest that influenza vaccination reduces the incidence of flu-like syndromes and laboratory-confirmed influenza in the elderly. There are no robust randomised trials specifically designed to assess whether vaccination of the elderly prevents influenza complications. Two case-control studies showed a statistical correlation between vaccination and a lower risk of death from influenza complications. Cohort studies have also shown that complications are less frequent when the vaccine strains correspond to circulating strains. Because of a patient selection bias, non-randomised studies seem to overestimate the efficacy of vaccination. Three randomised trials showed that vaccination of care home staff reduced mortality among elderly residents during seasonal flu epidemics. No such effect was observed in another trial, possibly because a large proportion (32%) of staff in the control institutions had also been vaccinated. In practice, influenza vaccination of the elderly with risk factors for complications is justified, especially for care home residents, their regular contacts and healthcare workers. Seasonal flu vaccination of healthy people over 65 provides limited benefit but its harm-benefit balance remains favourable. More studies of routine influenza vaccination of the elderly are needed.     

Cost-effectiveness analyses of hepatitis A vaccine: a systematic review to explore the effect of methodological quality on the economic attractiveness of vaccination strategies

Hepatitis A vaccines have been available for more than a decade. Because the burden of hepatitis A virus has fallen in developed countries, the appropriate role of vaccination programmes, especially universal vaccination strategies, remains unclear. Cost-effectiveness analysis is a useful method of relating the costs of vaccination to its benefits, and may inform policy. This article systematically reviews the evidence on the cost effectiveness of hepatitis A vaccination in varying populations, and explores the effects of methodological quality and key modelling issues on the cost-effectiveness ratios.Cost-effectiveness/cost-utility studies of hepatitis A vaccine were identified via a series of literature searches (MEDLINE, EMBASE, HSTAR and SSCI). Citations and full-text articles were reviewed independently by two reviewers. Reference searching, author searches and expert consultation ensured literature saturation. Incremental cost-effectiveness ratios (ICERs) were abstracted for base-case analyses, converted to $US, year 2005 values, and categorised to reflect various levels of cost effectiveness. Quality of reporting, methodological issues and key modelling issues were assessed using frameworks published in the literature.Thirty-one cost-effectiveness studies (including 12 cost-utility analyses) were included from full-text article review (n = 58) and citation screening (n = 570). These studies evaluated universal mass vaccination (n = 14), targeted vaccination (n = 17) and vaccination of susceptibles (i.e. individuals initially screened for antibody and, if susceptible, vaccinated) [n = 13]. For universal vaccination, 50% of the ICERs were <$US20 000 per QALY or life-year gained. Analyses evaluating vaccination in children, particularly in high incidence areas, produced the most attractive ICERs. For targeted vaccination, cost effectiveness was highly dependent on the risk of infection.Incidence, vaccine cost and discount rate were the most influential parameters in sensitivity analyses. Overall, analyses that evaluated the combined hepatitis A/hepatitis B vaccine, adjusted incidence for under-reporting, included societal costs and that came from studies of higher methodological quality tended to have more attractive cost-effectiveness ratios. Methodological quality varied across studies. Major methodological flaws included inappropriate model type, comparator, incidence estimate and inclusion/exclusion of costs.     

Antiviral agents for influenza: a comparison of cost-effectiveness data

The economic burden of influenza-related illness has been estimated to be 71.3-166 billion US dollars in the US, the majority of which is attributable to indirect costs as a result of lost productivity. There are currently four antiviral drugs available for the treatment of influenza: two ion channel blockers, amantadine and rimantadine; and two neuraminidase inhibitors, zanamivir and oseltamivir. The objective of this paper was to review the studies evaluating the cost effectiveness of currently available antiviral treatment and prophylaxis management strategies for influenza. Published studies that reported both costs and effectiveness of influenza management were extracted using MEDLINE, pre-MEDLINE and EMBASE. To facilitate a broad comparison, all costs were inflated to 2003 US dollars. Fifteen studies met the inclusion criteria of the review, with 14 analyses based on decision-analytic modelling and one economic analysis performed alongside a clinical trial. Management strategies included antiviral influenza prophylaxis or vaccination, empiric treatment of suspected disease, or antiviral treatment following rapid influenza testing. Study populations included healthy adults, adults at risk of influenza-related adverse outcomes, institutionalised and non-institutionalised elderly, and children. The comparator in all studies was standard care (i.e. over-the-counter medications only), and analyses were carried out from both the societal and payer perspectives. The only dominant strategy relative to standard care was vaccination of the institutionalised elderly. All other strategies in all populations were both more costly and more effective than standard care. Depending on the population and the perspective, the incremental cost-effectiveness ratios (ICERs) for antiviral treatment strategies ranged from 5000 US dollars/QALY for amantadine in test-and-treat studies to >400,000 US dollars/QALY for zanamivir or oseltamivir treatment in children. Sensitivity analysis in all studies consistently reported a strong influence of the population prevalence or diagnostic accuracy of influenza on the cost effectiveness of all strategies. Baseline influenza prevalence varied widely between studies, ranging from 15% to 68%. There was also a wide variation in the assumption about the disutility of influenza (ranging from -0.137 to -0.983 for the elderly requiring hospitalisation), which also impacted the cost effectiveness. Given the variation in the ICERs of antiviral treatment and prophylaxis, the uncertainty around many model parameters, and the dynamic nature of influenza from year to year, one can only conclude that antiviral treatment or prophylaxis for influenza is likely to be more cost effective in specific populations at specific times during the influenza season, and during influenza seasons when the population prevalence reaches epidemic levels or there is mismatch between the vaccine and the circulating virus.     

Influenza vaccination in the elderly: impact on hospitalisation and mortality

Influenza causes substantial morbidity across the age spectrum. However, the elderly are especially vulnerable to the serious complications of influenza that might result in hospitalisation or death, and high rates of influenza-associated excess hospitalisation or death that exceed by several-fold the rates seen among most other age groups have consistently been observed in many countries and across many seasons. Thus, the elderly are included among the high priority groups for routine influenza vaccination by many national health authorities. Inactivated influenza virus vaccines are widely available across the globe and are safe and effective. Vaccination of elderly persons has been associated with significant reductions in hospitalisations for pneumonia and influenza as well as hospitalisations for other cardiopulmonary disorders and even cerebrovascular disease. Vaccination has also been associated with reductions in influenza-associated and all-cause mortality during influenza seasons. The benefits of vaccination extend not only to community-dwelling elderly but also to elderly who reside in nursing homes. Likewise, vaccination provides benefits to the very old and to elderly persons with underlying co-morbidities as well as to the healthy elderly. Despite the substantially increased risk for serious complications and impressive benefits from vaccination among the elderly, influenza vaccine utilisation remains below target rates for this group in nearly all countries. The need for improved prevention and control of influenza is recognised as a priority for the global community--both to reduce the morbidity and mortality associated with epidemic influenza and to prepare for the next pandemic. Enhancing vaccine delivery to elderly persons would represent important progress toward that goal.     

Pharmacoeconomic Spotlight on Rotavirus Vaccine RIX4414 (Rotarix?) in Developed Countries

The most common cause of severe diarrhea in infants and young children is rotavirus gastroenteritis (RVGE), which is associated with significant morbidity, healthcare resource use, and direct and indirect costs in industrialized nations. The monovalent rotavirus vaccine RIX4414 (Rotarix™) is administered as a two-dose oral series in infants and has demonstrated protective efficacy against RVGE in clinical trials conducted in developed countries. In addition, various naturalistic studies have demonstrated ‘real-world’ effectiveness after the introduction of widespread rotavirus vaccination programs in the community setting.Numerous cost-effectiveness analyses have been conducted in developed countries in which a universal rotavirus vaccination program using RIX4414 was compared with no universal rotavirus vaccination program. There was a high degree of variability in base-case results across studies even when the studies were conducted in the same country, often reflecting differences in the selection of data sources or assumptions used to populate the models. In addition, results were sensitive to plausible changes in a number of key input parameters. As such, it is not possible to definitively state whether a universal rotavirus vaccination program with RIX4414 is cost effective in developed countries, although results of some analyses in some countries suggest this is the case. In addition, international guidelines advocate universal vaccination of infants and children against rotavirus. It is also difficult to draw conclusions regarding the cost effectiveness of rotavirus vaccine RIX4414 relative to that of the pentavalent rotavirus vaccine, which is administered as a three-dose oral series. Although indirect comparisons in cost-effectiveness analyses indicate that RIX4414 provided more favorable incremental cost-effectiveness ratios when each vaccine was compared with no universal rotavirus vaccination program, results were generally sensitive to vaccine costs. Actual tender prices of a full vaccination course for each vaccine were not known at the time of the analyses and therefore had to be estimated.     

Cost-effectiveness analysis of pneumococcal vaccination for elderly individuals in The Netherlands

OBJECTIVE: To assess the cost effectiveness (net costs per life year gained) of pneumococcal vaccination of elderly individuals aged 65 years and over in The Netherlands. DESIGN AND SETTING: A pharmacoeconomic analysis was conducted from the healthcare perspective in The Netherlands. The gender- and age-specific modelling framework linked epidemiological aspects of invasive pneumococcal disease (e.g. incidence, mortality, life years lost) to vaccination and hospital resource use. To derive 90% confidence limits for net costs per life year gained a stochastic analysis was performed. INTERVENTION: Pneumococcal vaccination in the elderly with the 23-valent vaccine. Effectiveness of the vaccine in preventing invasive pneumococcal disease was derived from international studies. MAIN OUTCOME MEASURES AND RESULTS: Pneumococcal vaccination in the elderly was not found to be cost saving. At baseline, stochastic and univariate sensitivity analysis net costs per life year gained were estimated to be between 6000 and 16,000 euro (EUR) [EUR1 = 1.1 US dollars; cost level 1995]. A scenario analysis on alternative age-dependent vaccination strategies indicated even higher net costs per life year gained, up to EUR28,000 for vaccinating only those elderly aged 85 years and over. CONCLUSIONS: Pneumococcal vaccination is associated with net costs per life year gained of EUR10,100 (at baseline assumptions). These costs are higher than those for influenza vaccination (EUR5500). Our pharmacoeconomic approach, which needs to be considered in conjunction with social, psychological and budgetary issues, is intended to contribute to rational decision-making in healthcare policy.     

Cost benefit and cost effectiveness of antifungal prophylaxis in immunocompromised patients treated for haematological malignancies: reviewing the available evidence

There has been a large increase in the incidence of invasive fungal infections (IFIs) over the past decades, largely because of the increasing size of the population at risk. One of the major risk groups for IFIs are patients with haematological malignancies treated with cytotoxic chemotherapy or undergoing haematopoietic stem cell transplantation. These IFIs are associated with high morbidity and mortality rates. Consequently, as the diagnosis of IFIs is difficult, antifungal prophylaxis is desirable in high-risk patients. Furthermore, as the economic impact of IFIs is also significant, it is important to assess the cost benefit and cost effectiveness of each prophylactic agent in order to aid decisions concerning which prophylactic agent provides the best value for limited healthcare resources. This article systematically reviews the available pharmacoeconomic evidence regarding antifungal prophylaxis in immunocompromised patients treated for haematological malignancies. Furthermore, specific points of interest concerning economic analyses of antifungal prophylaxis are briefly discussed. Considering the available evidence, antifungal prophylaxis in immunocompromised patients treated for haematological malignancies seems to be an intervention with favourable cost-benefit, cost-effectiveness and cost-saving potential. Furthermore, recently introduced antifungal agents seem to be attractive alternatives to fluconazole from a pharmacoeconomic point of view. However, due to wide heterogeneity in patient characteristics, underlying diseases, hospital settings and study methods in the included economic studies, as well as the lack of 'head-to-head' trials, it is difficult to find clear evidence of the economic advantages of a single prophylactic agent. Furthermore, we show that the results of cost-effectiveness analyses are highly dependent on several crucial factors that influence the baseline IFI incidence rates and, therefore, differ per patient population or region.     

Cost effectiveness of oseltamivir treatment for patients with influenza-like illness who are at increased risk for serious complications of influenza: illustration for the Netherlands

BACKGROUND: Oseltamivir is effective in the treatment of influenza. Utilisation in The Netherlands is limited, but increasing. OBJECTIVE: To estimate the cost effectiveness of oseltamivir treatment (vs symptom relief only) for patients with influenza-like illness (ILI) who are at increased risk for serious complications of influenza. METHODS: A cost-effectiveness analysis was used, building on a previously developed model (decision tree) that was applied for evaluating influenza vaccination and pandemic preparedness plans. Three patient subgroups were assessed (elderly patients [aged > or = 65 years] without chronic disease, elderly patients with chronic disease, and chronically ill, non-elderly patients). Inputs for the model were taken from various sources including a meta-analysis. A societal perspective was adopted and costs were expressed in euro per life-year gained (year 2003 values). Life-years lost were discounted at 4% in accordance with Dutch guidelines. Deterministic and probabilistic sensitivity analyses were employed to assess the robustness of the results. RESULTS: For chronically ill patients with ILI, visits to the GP for oseltamivir treatment were cost saving. For non-chronically ill elderly patients, incremental cost-effectiveness was estimated at 1759 euros per life-year gained. Cost savings and favourable cost effectiveness were robust in a deterministic and stochastic sensitivity analysis. CONCLUSION: Our model-based analysis suggests that at-risk people presenting with ILI to a GP could be offered oseltamivir at favourable cost effectiveness or even cost savings in the Dutch setting compared with symptom relief with analgesics only.     

Quetiapine: a pharmacoeconomic review of its use in bipolar disorder

This article briefly summarizes the burden of bipolar disorder and the clinical profile of quetiapine (Seroquel?) in the management of bipolar disorder, followed by a detailed review of pharmacoeconomic analyses. Quetiapine is an atypical antipsychotic that is available in numerous countries as immediate-release and extended-release tablets for the treatment of major psychiatric disorders, including bipolar disorder. Randomized, double-blind, placebo-controlled trials with quetiapine have demonstrated its efficacy in bipolar I and II disorders, and the drug has been generally well tolerated in clinical trials. Three cost-effectiveness analyses of maintenance therapy in bipolar I disorder, which used similar Markov models and incorporated data from key clinical trials and a number of other sources, showed that quetiapine, as adjunctive therapy with mood stabilizers (lithium or divalproex), was a cost-effective treatment option from the healthcare payer perspective in the UK and the US. Quetiapine either dominated comparators (typically mood stabilizers alone) or was associated with incremental cost-effectiveness ratios that were usually well below widely accepted thresholds of cost effectiveness. One of the studies evaluated extended-release quetiapine, although clinical efficacy data used in the Markov model were for the immediate-release formulation. In another analysis, which used a discrete-event simulation model and was conducted from the perspective of the UK healthcare payer, quetiapine monotherapy was cost effective compared with olanzapine monotherapy as maintenance treatment for all phases of bipolar I or II disorder. In this model, favourable results were also shown for quetiapine (with or without mood stabilizers) compared with a wide range of maintenance therapy regimens. Another modelled analysis conducted from the UK healthcare payer perspective showed that quetiapine was dominated by haloperidol in the short-term treatment of a manic episode in patients with bipolar I disorder. Both favourable and unfavourable results have been reported in cost analyses of quetiapine in bipolar disorder (type I or type not specified). Possible explanations for some of the variability in results of the pharmacoeconomic analyses include heterogeneity among the models in terms of input parameters or assumptions in the base-case analyses, country- or region-specific differences in estimates of healthcare resource use and associated costs, variability in treatment alternatives, and differences in the year of costing and discounting used in the analyses. In addition, some of the studies had short time horizons and focused on acute manic episodes only, whereas others were longer-term analyses that considered the full spectrum of health states in patients with bipolar disorder. Various limitations of the studies have been recognized, and results from one country may not be applicable to other countries. In conclusion, results of available pharmacoeconomic analyses provide evidence of the cost effectiveness of quetiapine as an adjunct to mood stabilizers for maintenance therapy in (primarily type I) bipolar disorder from a healthcare payer perspective in the UK and the US. Some evidence is available to support the cost effectiveness of quetiapine monotherapy or the use of extended-release quetiapine as adjunctive therapy with mood stabilizers in this setting, although further analyses appear to be warranted. Whether these findings apply to other geographical regions requires further study. Evidence for the long-term (>2-year) cost effectiveness of quetiapine in bipolar disorder is currently limited and further studies are also needed to address the cost effectiveness of quetiapine from a societal perspective and in bipolar II disorder.     

Cost-effectiveness analysis of pneumococcal vaccination of adults and elderly persons in Belgium

OBJECTIVE: To analyse the direct medical costs and effectiveness of vaccinating adults aged between 18 and 64 years and elderly persons > or = 65 years of age with the 23-valent pneumococcal polysaccharide vaccine. DESIGN AND SETTING: This was a decision-analytic modelling study from the societal perspective in Belgium. The analysis compared 'vaccination' with 'no vaccination and treatment'. METHODS: Calculations were based on the assumption that vaccination is as effective against all pneumococcal infections as it is against invasive pneumococcal disease. Data on the incidence of pneumococcal pneumonia and meningitis, frequency of hospitalisation, mortality rates and vaccine effectiveness were derived from the international literature. Costs were derived from analysis of historical data for cases of pneumococcal infection in Belgium. RESULTS: Vaccinating 1000 adults between the ages of 18 and 64 years gains approximately 2 life-years in comparison with the no vaccination option. However, to realise these additional health benefits requires additional costs of 11,800 European Currency Units (ECU; 1995 values) per life-year saved. Vaccinating 1000 elderly people (> or = 65 years) leads to > 9 life-years gained as well as a small monetary benefit of ECU1250. An extensive sensitivity analysis did not greatly affect the results for the elderly population: vaccination in this age group always remained favourable, and thus it is clearly indicated from an economic point of view. A crucial assumption for both age groups is that the effectiveness of the vaccine holds for all pneumococcal pneumonia. It is clear that the results will become less favourable if this assumption is dropped. CONCLUSIONS: Preventing pneumococcal infections by vaccination clearly benefits people's health. Reimbursement can be recommended for the elderly group; however, more accurate epidemiological data are still needed to make decisions concerning routine pneumococcal vaccination in adults < 65 years of age. Unfortunately, the issue of whether the effectiveness of the vaccine holds for all pneumococcal pneumonia is as yet unresolved in the medical literature.     

Economic evaluations of childhood influenza vaccination: a critical review

The potential benefits of influenza vaccination programmes targeted at children have gained increasing attention in recent years. We conducted a literature search of economic evaluations of influenza vaccination in those aged ≤18 years. The search revealed 20 relevant articles, which were reviewed. The studies differed widely in terms of the costs and benefits that were included. The conclusions were generally favourable for vaccination, but often applied a wider perspective (i.e. including productivity losses) than the reference case for economic evaluations used in many countries. Several evaluations estimated outcomes from a single-year epidemiological study, which may limit their validity given the year-to-year variation in influenza transmissibility, virulence, vaccine match and prior immunity. Only one study used a dynamic transmission model able to fully incorporate the indirect herd protection to the wider community. The use of dynamic models offers great scope to capture the population-wide implications of seasonal vaccination efforts, particularly those targeted at children.     

Is there a role for a mucosal influenza vaccine in the elderly?

Influenza infection is an acute respiratory disease with a high morbidity and significant mortality, particularly among the elderly and individuals with chronic diseases. The majority of countries now recommend annual influenza vaccination for all people aged 65 years or older, and for those with high risk conditions. Most commercially available influenza vaccines are administered systemically and while these are effective in children and young adults, efficacy levels in elderly individuals have been reported to be much lower. Mucosal vaccines may offer an improved vaccine strategy for protection of the elderly. As the influenza virus causes a respiratory infection, it is potentially more beneficial to administer a vaccine that will boost protection in the mucosal surfaces of the upper and lower respiratory tract. Mucosal influenza vaccines are aimed at stimulating protective immunity in the respiratory tract via oral or intranasal immunisation. This review examines our present knowledge of mucosal immunity and current strategies for mucosal vaccination. It also stresses that the use of serum antibody levels as a 'surrogate marker' for protection against influenza is potentially misleading; serum antibody, for example, may be a quite inappropriate marker to assess a mucosal vaccine. This marker does not reflect other immune responses to vaccination that are crucial for protection.     

Spotlight on the pharmacoeconomics of escitalopram in depression

Escitalopram (Cipralex), a new highly selective inhibitor of serotonin reuptake, is the active S-enantiomer of RS-citalopram. It is effective in the treatment of patients with major depressive disorder (MDD) and may have a faster onset of therapeutic effect than citalopram. It has also been shown to lead to improvements in measures of quality of life (QOL). Escitalopram is generally well tolerated, with nausea being the most common adverse event associated with its use. Modelled pharmacoeconomic analyses found escitalopram to have a cost-effectiveness and cost-utility advantage over other SSRIs, including generic citalopram and fluoxetine and branded sertraline, and also over the serotonin-noradrenaline reuptake inhibitor (SNRI) venlafaxine extended-release (XR). These studies used a decision-analytic approach with a 6-month time horizon and were performed in Western Europe (year of costing 2000 or 2001). Cost-effectiveness ratios for escitalopram, in terms of cost per successfully treated patient over 6 months, ranged from euro871 to euro2598 in different countries, based on direct costs and remission rates, and were consistently lower (i.e. more favourable) than the ratios for comparators (euro970-euro3472). Outcomes similarly favoured escitalopram when indirect costs (represented by those associated with sick leave and loss of productivity) were included. The results of comparisons with citalopram, fluoxetine and sertraline were not markedly affected by changes to assumptions in sensitivity analyses, although comparisons with venlafaxine XR were sensitive to changes in the remission rate. The mean number of quality-adjusted life years gained during the 6-month period was similar for all drugs evaluated, but direct costs were lower with escitalopram, leading to lower cost-utility ratios than for comparators. Incremental analyses performed in two of the studies confirmed the cost-effectiveness and cost-utility advantage of escitalopram. A prospective, 8-week comparative pharmacoeconomic analysis found that escitalopram achieved similar efficacy to venlafaxine XR, but was associated with 40% lower direct costs (euro85 vs euro142 per patient over 8 weeks; 2001 costs), although this difference did not reach statistical significance. In both the modelled and prospective analyses, the differences in overall direct costs were mainly due to lower secondary care costs (in particular those related to hospitalisation) with escitalopram. In the prospective analysis, escitalopram had lower estimated drug acquisition costs than venlafaxine XR. CONCLUSION: Escitalopram, the S-enantiomer of RS-citalopram and a highly selective inhibitor of serotonin reuptake, is an effective antidepressant in patients with MDD, has a favourable tolerability profile, and, on the basis of available data, appears to have a rapid onset of therapeutic effect. Modelled pharmacoeconomic analyses from Western Europe suggest that it may be a cost-effective alternative to generic citalopram, generic fluoxetine and sertraline. Although the available data are less conclusive in comparison with venlafaxine XR, escitalopram is at least as cost effective as the SNRI based on a prospective study, and potentially more cost effective based on modelled analyses. Overall, clinical and pharmacoeconomic data support the use of escitalopram as first-line therapy in patients with MDD.     

人乳头瘤病毒疫苗预防中国女性宫颈癌药物经济学研究的系统评价

目的 系统评价人乳头瘤病毒（human papillomavirus,HPV）疫苗预防中国女性宫颈癌的药物经济学特性。方法 计算机检索PubMed、EMbase、中国知网（CNKI）、万方数据库（Wanfang Data）、维普数据库（CQVIP）、中国生物医学文献数据库（China Biology Medicine,CBM）等数据库,搜集关于HPV疫苗预防中国女性宫颈癌的药物经济学研究,检索时间从建库截至2020年2月。由2名研究者根据标准独立筛选文献、提取资料并使用卫生经济学评价报告标准共识（Consolidated Health Economic Evaluation Reporting Standards,CHEERS）和卫生经济研究质量评价（Quality of Health Economic Studies,QHES）对纳入文献进行质量评价,随后进行描述性分析。结果 共纳入15篇研究,其中4篇为成本效果研究,剩余11篇均为成本效用研究。9项研究来自中国大陆,5项来自中国台湾,1项来自中国香港,文献质量均较高。相比仅进行宫颈癌筛查和不干预,接种HPV疫苗合并进行宫颈癌筛查在无HPV感染史女性当中更具有经济性,但不同价型HPV疫苗之间的经济性结果不一致。结论 建议HPV疫苗纳入医保以及增加相关财政资金的投入,并且对不同价型HPV疫苗之间的经济性进行进一步的研究。     

Seasonal influenza vaccination of healthy working-age adults: a review of economic evaluations

The recent impact of influenza on the working-age population of the US has led to changes in the recommendations for vaccination against seasonal influenza; however, the implications of vaccinating such a population have been debated. A review of cost-effectiveness analyses of vaccinating the working-age population of the US against seasonal influenza was conducted using articles published between January 1990 and January 2010. Studies considered for inclusion were identified using MEDLINE, EMBASE and Econlit. Reviewers worked in pairs, and each team member independently extracted relevant data using a standard abstraction form. The source and appropriateness of parameters (epidemiological data, probabilities and costs), the designs employed and the sufficiency of sensitivity analysis were considered during review. Key inputs extracted from the selected studies included influenza or influenza-like illness attack rates, outpatient visits averted, total vaccination days and lost workdays. Seven studies were identified as appropriate for this review. All studies were conducted in the US and from the societal perspective; three were randomized controlled trials and the remaining four were economic simulation models comparing vaccination and influenza antiviral drugs or no intervention; analyses focused on healthy working-age adults aged 18-49 years. Results ranged from net savings of $US68.96 to net costs of $US85.92 per person vaccinated (four studies) and net costs of $US104-1005 per episode of influenza averted (one study). Only two studies reported cost-effectiveness ratios; these ranged from $US26,565 to $US50,512 per quality-adjusted life-year gained. Nearly all of the studies conducted sensitivity analysis; results were most sensitive to variation in wage rates, levels of worker productivity, the costs and effectiveness of vaccination, and the rate of influenza illness. Review of the included studies suggests that seasonal influenza vaccination of healthy, working-age adults is generally not cost saving, requiring an investment to generate health benefits. The decision to vaccinate such a group will depend upon the societal and payer valuation of those benefits.