Higher-valency pneumococcal conjugate vaccines in older adults, taking into account indirect effects from childhood vaccination: a cost-effectiveness study for the Netherlands.

BACKGROUND: New 15- and 20-valent pneumococcal vaccines (PCV15, PCV20) are available for both children and adults, while PCV21 for adults is in development. However, their cost-effectiveness for older adults, taking into account indirect protection and serotype replacement from a switch to PCV15 and PCV20 in childhood vaccination, remains unexamined. METHODS: We used a static model for the Netherlands to assess the cost-effectiveness of different strategies with 23-valent pneumococcal polysaccharide vaccine (PPV23), PCV15, PCV20, and PCV21 for a 65-year-old cohort from a societal perspective, over a 15-year time horizon. Childhood vaccination was varied from PCV10 to PCV13, PCV15, and PCV20. Indirect protection was assumed to reduce the incidence of vaccine serotypes in older adults by 80% (except for serotype 3, no effect), completely offset by an increase in non-vaccine serotype incidence due to serotype replacement. RESULTS: Indirect effects from childhood vaccination reduced the cost-effectiveness of vaccination of older adults, depending on the serotype overlap between the vaccines. With PCV10, PCV13, or PCV15 in children, PCV20 was more effective and less costly for older adults than PPV23 and PCV15. PCV20 costs approximately €10,000 per quality-adjusted life year (QALY) gained compared to no pneumococcal vaccination, which falls below the conventional Dutch €20,000/QALY gained threshold. However, with PCV20 in children, PCV20 was no longer considered cost-effective for older adults, costing €22,550/QALY gained. As indirect effects progressed over time, the cost-effectiveness of PCV20 for older adults further diminished for newly vaccinated cohorts. PPV23 was more cost-effective than PCV20 for cohorts vaccinated 3 years after the switch to PCV20 in children. PCV21 offered the most QALY gains, and its cost-effectiveness was minimally affected by indirect effects due to its coverage of 11 different serotypes compared to PCV20. CONCLUSIONS: For long-term cost-effectiveness in the Netherlands, the pneumococcal vaccine for older adults should either include invasive serotypes not covered by childhood vaccination or become more affordable than its current pricing for individual use.

Age-specific severity of severe acute respiratory syndrome coronavirus 2 in February 2020 to June 2021 in the Netherlands.

Background: The severity of Severe Acute Respiratory Syndrome Coronavirus 2 infection varies with age and time. Here, we quantify how age-specific risks of hospitalization, intensive care unit (ICU) admission, and death upon infection changed from February 2020 to June 2021 in the Netherlands. Methods: A series of large representative serology surveys allowed us to estimate age-specific numbers of infections in three epidemic periods (late-February 2020 to mid-June 2020, mid-June 2020 to mid-February 2021, and mid-February 2021 to late-June 2021). We accounted for reinfections and breakthrough infections. Severity measures were obtained by combining infection numbers with age-specific numbers of hospitalization, ICU admission, and excess all-cause deaths. Results: There was an accelerating, almost exponential, increase in severity with age in each period. The rate of increase with age was the highest for death and the lowest for hospitalization. In late-February 2020 to mid-June 2020, the overall risk of hospitalization upon infection was 1.5% (95% confidence interval [CI] 1.3-1.8%), the risk of ICU admission was 0.36% (95% CI: 0.31-0.42%), and the risk of death was 1.2% (95% CI: 1.0-1.4%). The risk of hospitalization was significantly increased in mid-June 2020 to mid-February 2021, while the risk of ICU admission remained stable over time. The risk of death decreased over time, with a significant drop among ≥70-years-olds in mid-February 2021 to late-June 2021; COVID-19 vaccination started early January 2021. Conclusion: Whereas the increase in severity of Severe Acute Respiratory Syndrome Coronavirus 2 with age remained stable, the risk of death upon infection decreased over time. A significant drop in risk of death among elderly coincided with the introduction of COVID-19 vaccination.

A scenario modelling analysis to anticipate the impact of COVID-19 vaccination in adolescents and children on disease outcomes in the Netherlands, summer 2021.

BackgroundSince the roll-out of COVID-19 vaccines in late 2020 and throughout 2021, European governments have relied on mathematical modelling to inform policy decisions about COVID-19 vaccination.AimWe present a scenario-based modelling analysis in the Netherlands during summer 2021, to inform whether to extend vaccination to adolescents (12-17-year-olds) and children (5-11-year-olds).MethodsWe developed a deterministic, age-structured susceptible-exposed-infectious-recovered (SEIR) model and compared modelled incidences of infections, hospital and intensive care admissions, and deaths per 100,000 people across vaccination scenarios, before the emergence of the Omicron variant.ResultsOur model projections showed that, on average, upon the release of all non-pharmaceutical control measures on 1 November 2021, a large COVID-19 wave may occur in winter 2021/22, followed by a smaller, second wave in spring 2022, regardless of the vaccination scenario. The model projected reductions in infections/severe disease outcomes when vaccination was extended to adolescents and further reductions when vaccination was extended to all people over 5 years-old. When examining projected disease outcomes by age group, individuals benefitting most from extending vaccination were adolescents and children themselves. We also observed reductions in disease outcomes in older age groups, particularly of parent age (30-49 years), when children and adolescents were vaccinated, suggesting some prevention of onward transmission from younger to older age groups.ConclusionsWhile our scenarios could not anticipate the emergence/consequences of SARS-CoV-2 Omicron variant, we illustrate how our approach can assist decision making. This could be useful when considering to provide booster doses or intervening against future infection waves.

Targeted Screening for Chronic Q Fever, the Netherlands.

Early detection of and treatment for chronic Q fever might prevent potentially life-threatening complications. We performed a chronic Q fever screening program in general practitioner practices in the Netherlands 10 years after a large Q fever outbreak. Thirteen general practitioner practices located in outbreak areas selected 3,419 patients who had specific underlying medical conditions, of whom 1,642 (48%) participated. Immunofluorescence assay of serum showed that 289 (18%) of 1,642 participants had a previous Coxiella burnetii infection (IgG II titer >1:64), and 9 patients were suspected of having chronic Q fever (IgG I y titer >1:512). After medical evaluation, 4 of those patients received a chronic Q fever diagnosis. The cost of screening was higher than estimated earlier, but the program was still cost-effective in certain high risk groups. Years after a large Q fever outbreak, targeted screening still detected patients with chronic Q fever and is estimated to be cost-effective.

Consultations for Influenza-Like Illness in Primary Care in The Netherlands: A Regression Approach.

OBJECTIVES: To estimate the general practitioner (GP) consultation rate attributable to influenza in The Netherlands. METHODS: Regression analysis was performed on the weekly numbers of influenza-like illness (ILI) GP consultations and laboratory reports for influenza virus types A and B and 8 other pathogens over the period 2003-2014 (11 influenza seasons; week 40-20 of the following year). RESULTS: In an average influenza season, 27% and 11% of ILI GP consultations were attributed to infection by influenza virus types A and B, respectively. Influenza is therefore responsible for approximately 107 000 GP consultations (651/100 000) each year in The Netherlands. GP consultation rates associated with influenza infection were highest in children under 5 years of age, at 667 of 100 000 for influenza A and 258 of 100 000 for influenza B. Influenza virus infection was found to be the predominant cause of ILI-related GP visits in all age groups except children under 5, in which respiratory syncytial virus (RSV) infection was found to be the main contributor. CONCLUSIONS: The burden of influenza in terms of GP consultations is considerable. Overall, influenza is the main contributor to ILI. Although ILI symptoms in children under 5 years of age are most often associated with RSV infection, the majority of visits related to influenza occur among children under 5 years of age.

Cost-Effectiveness of Pediatric Influenza Vaccination in The Netherlands.

OBJECTIVE: This study evaluates the cost-effectiveness of extending the Dutch influenza vaccination program for elderly and medical high-risk groups to include pediatric influenza vaccination, taking indirect protection into account. METHODS: An age-structured dynamic transmission model was used that was calibrated to influenza-associated GP visits over 4 seasons (2010-2011 to 2013-2014). The clinical and economic impact of different pediatric vaccination strategies were compared over 20 years, varying the targeted age range, the vaccine type for children or elderly and high-risk groups. Outcome measures include averted symptomatic infections and deaths, societal costs and quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Costs and QALYs were discounted at 4% and 1.5% annually. RESULTS: At an assumed coverage of 50%, adding pediatric vaccination for 2- to 17-year-olds with quadrivalent live-attenuated vaccine to the current vaccination program for elderly and medical high-groups with quadrivalent inactivated vaccine was estimated to avert, on average, 401 820 symptomatic cases and 72 deaths per year. Approximately half of averted symptomatic cases and 99% of averted deaths were prevented in other age groups than 2- to 17-year-olds due to herd immunity. The cumulative discounted 20-year economic impact was 35 068 QALYs gained and €1687 million saved, that is, the intervention was cost-saving. This vaccination strategy had the highest probability of being the most cost-effective strategy considered, dominating pediatric strategies targeting 2- to 6-year-olds or 2- to 12-year-olds or strategies with trivalent inactivated vaccine. CONCLUSION: Modeling indicates that introducing pediatric influenza vaccination in The Netherlands is cost-saving, reducing the influenza-related disease burden substantially.

Occupation- and age-associated risk of SARS-CoV-2 test positivity, the Netherlands, June to October 2020.

High coronavirus incidence has prompted the Netherlands to implement a second lockdown. To elucidate the epidemic's development preceding this second wave, we analysed weekly test positivity in public test locations by population subgroup between 1 June and 17 October 2020. Hospitality and public transport workers, driving instructors, hairdressers and aestheticians had higher test positivity compared with a reference group of individuals without a close-contact occupation. Workers in childcare, education and healthcare showed lower test positivity.

Cost-effectiveness of Screening Program for Chronic Q Fever, the Netherlands.

In the aftermath of a large Q fever (QF) epidemic in the Netherlands during 2007-2010, new chronic QF (CQF) patients continue to be detected. We developed a health-economic decision model to evaluate the cost-effectiveness of a 1-time screening program for CQF 7 years after the epidemic. The model was parameterized with spatial data on QF notifications for the Netherlands, prevalence data from targeted screening studies, and clinical data from the national QF database. The cost-effectiveness of screening varied substantially among subpopulations and geographic areas. Screening that focused on cardiovascular risk patients in areas with high QF incidence during the epidemic ranged from cost-saving to €31,373 per quality-adjusted life year gained, depending on the method to estimate the prevalence of CQF. The cost per quality-adjusted life year of mass screening of all older adults was €70,000 in the most optimistic scenario.

Vaccinating children against influenza: overall cost-effective with potential for undesirable outcomes.

BACKGROUND: The present study aims to assess the cost-effectiveness of an influenza vaccination program for children in the Netherlands. This requires an evaluation of the long-term impact of such a program on the burden of influenza across all age groups, using a transmission model that accounts for the seasonal variability in vaccine effectiveness and the shorter duration of protection following vaccination as compared to natural infection. METHODS: We performed a cost-effectiveness analysis based on a stochastic dynamic transmission model that has been calibrated to reported GP visits with influenza-like illness in the Netherlands over 11 seasons (2003/2004 to 2014/2015). We analyzed the costs and effects of extending the current program with vaccination of children aged 2-16 years at 50% coverage over 20 consecutive seasons. We measured the effects in quality-adjusted life-years (QALYs) and we adopted a societal perspective. RESULTS: The childhood vaccination program is estimated to have an average incremental cost-effectiveness ratio (ICER) of €3944 per QALY gained and is cost-effective in the general population (across 1000 simulations; conventional Dutch threshold of €20,000 per QALY gained). The childhood vaccination program is not estimated to be cost-effective for the target-group itself with an average ICER of €57,054 per QALY gained. Uncertainty analyses reveal that these ICERs hide a wide range of outcomes. Even though introduction of a childhood vaccination program decreases the number of infections, it tends to lead to larger epidemics: in 23.3% of 1000 simulations, the childhood vaccination program results in an increase in seasons with a symptomatic attack rate larger than 5%, which is expected to cause serious strain on the health care system. In 6.4% of 1000 simulations, the childhood vaccination program leads to a net loss of QALYs. These findings are robust across different targeted age groups and vaccination coverages. CONCLUSIONS: Modeling indicates that childhood influenza vaccination is cost-effective in the Netherlands. However, childhood influenza vaccination is not cost-effective when only outcomes for the children themselves are considered. In approximately a quarter of the simulations, the introduction of a childhood vaccination program increases the frequency of seasons with a symptomatic attack rate larger than 5%. The possibility of an overall health loss cannot be excluded.

Trends in governmental expenditure on vaccination programmes in the Netherlands, a historical analysis.

BACKGROUND: Health economic evaluations are often required before implementing a vaccination programme. Such evaluations rarely consider the historical context of a vaccination programme. We review the financial history of vaccination programmes in the Netherlands, and compare these to demographic and macroeconomic developments as well as avoided mortality burden. METHODS: Previously uncatalogued historical expenditures on the Dutch National Immunisation Programme (NIP) and influenza vaccination were obtained from official reports. Costs were adjusted for inflation using Consumer Price Indices and expressed in Euro of 2016. Estimates on mortality burden averted were obtained from previous research and used to calculate the ratio of expenses to averted mortality burden for vaccinations against diphtheria, tetanus, pertussis, polio, measles, mumps and rubella for birth cohorts 1953-1992. RESULTS: Developments towards a uniform government funded NIP started early 1950s with vaccinations against diphtheria, pertussis and tetanus, culminating in its official launch in 1957 together with polio vaccinations. Since the 1980s, expenditure increased nearly five-fold mostly due to the addition of new vaccines, while spending on already implemented vaccinations tended to decline. Overall, expenditure increased from € 5 million in 1957 to € 93 million in 2014. Relative to total healthcare expenditure, the NIP contributed little, ranging between 0.05% and 0.14%. Spending on influenza vaccination increased from € 37 million in 1996 to € 52 million in 2014, while relative to total healthcare expenditure it decreased from 0.069% to 0.055%. In 2014, 0.15% of healthcare expenditure and € 533 per birth was spent on vaccination programmes. Overall, for birth cohorts 1953-1992, € 5.4 thousand (95% confidence interval: 4.0-7.3) was expended per year-of-life-lost averted. CONCLUSION: The actual costs per year-of-life gained are more favorable than estimated here since averted medical costs were not included. Although expenditure on vaccination programmes increased substantially, the contribution to overall healthcare expenditure remained small.

Cost-effectiveness of vaccination of immunocompetent older adults against herpes zoster in the Netherlands: a comparison between the adjuvanted subunit and live-attenuated vaccines.

BACKGROUND: The newly registered adjuvanted herpes zoster subunit vaccine (HZ/su) has a higher efficacy than the available live-attenuated vaccine (ZVL). National decision-makers soon need to decide whether to introduce HZ/su or to prefer HZ/su above ZVL. METHODS: Using a Markov model with a decision tree, we conducted a cost-effectiveness analysis of vaccination with HZ/su (two doses within 2 months) or zoster vaccine live (ZVL) (single dose, or single dose with a booster after 10 years) for cohorts of 50-, 60-, 70- or 80-year-olds in the Netherlands. The model was parameterized using vaccine efficacy data from randomized clinical trials and up-to-date incidence, costs and health-related quality of life data from national datasets. We used a time horizon of 15 years, and the analysis was conducted from the societal perspective. RESULTS: At a coverage of 50%, vaccination with two doses of HZ/su was estimated to prevent 4335 to 10,896 HZ cases, depending on the cohort age. In comparison, this reduction was estimated at 400-4877 for ZVL and 427-6466 for ZVL with a booster. The maximum vaccine cost per series of HZ/su to remain cost-effective to a willingness-to-pay threshold of €20,000 per quality-adjusted life year (QALY) gained ranged from €109.09 for 70-year-olds to €63.68 for 50-year-olds. The cost-effectiveness of ZVL changed considerably by age, with corresponding maximum vaccine cost per dose ranging from €51.37 for 60-year-olds to €0.73 for 80-year-olds. Adding a ZVL booster after 10 years would require a substantial reduction of the maximum cost per dose to remain cost-effective as compared to ZVL single dose. Sensitivity analyses on the vaccine cost demonstrated that there were scenarios in which vaccination with either HZ/su (two doses), ZVL single dose or ZVL + booster could be the most cost-effective strategy. CONCLUSIONS: A strategy with two doses of HZ/su was superior in reducing the burden of HZ as compared to a single dose or single dose + booster of ZVL. Both vaccines could potentially be cost-effective to a conventional Dutch willingness-to-pay threshold for preventive interventions. However, whether HZ/su or ZVL would be the most cost-effective alternative depends largely on the vaccine cost.

Secondary adherence to non-vitamin-K antagonist oral anticoagulants in patients with atrial fibrillation in Sweden and the Netherlands.

OBJECTIVE: There is limited evidence on patients' adherence and the impact of the prescribed dosing regimen in non-vitamin-K oral anticoagulants (NOACs). We aimed to assess secondary adherence to NOACs and to determine the impact of the dosing regimen in patients with atrial fibrillation. METHODS: Patients using a NOAC between 2009 and 2013 were identified from the nation-wide Swedish Prescribed Drug Register and the Dutch regional IADB.nl database. Patients using a consistent dosage for at least 180 consecutive days were included. Adherence was calculated using the medication possession ratio (MPR) and adjusted for overlapping dates. Adherence was defined as a MPR ≥0.8. Sensitivity analyses were performed using a MPR ≥0.9. Logistic regression was performed to compare secondary adherence and to explore the influence of the dosing regimen. RESULTS: A total of 5254 Swedish and 430 Dutch NOAC users were included. The mean MPR was 96.0% (SD 7.8%) in Sweden and 95.1% (SD 10.1%) in the Netherlands. Multivariable logistic regression analysis showed that a twice daily regimen had a lower likelihood of being secondary adherent compared to a once daily regimen in Sweden (odds ratio [OR] 0.21 [95% CI 0.12-0.35]). LIMITATIONS: The influence of selection bias introduced by the inclusion criterion of ≥2 dispensations covering at least 180 days could not be excluded. CONCLUSIONS: This study demonstrated that secondary adherence was high in this specific setting among patients with at least two initial dispensations of a NOAC covering a minimum of 180 days. The use of NOACs in a once daily regimen showed higher adherence compared to a twice daily regimen.

The cost-effectiveness of trivalent and quadrivalent influenza vaccination in communities in South Africa, Vietnam and Australia.

BACKGROUND: To inform national healthcare authorities whether quadrivalent influenza vaccines (QIVs) provide better value for money than trivalent influenza vaccines (TIVs), we assessed the cost-effectiveness of TIV and QIV in low-and-middle income communities based in South Africa and Vietnam and contrasted these findings with those from a high-income community in Australia. METHODS: Individual based dynamic simulation models were interfaced with a health economic analysis model to estimate the cost-effectiveness of vaccinating 15% of the population with QIV or TIV in each community over the period 2003-2013. Vaccination was prioritized for HIV-infected individuals, before elderly aged 65+ years and young children. Country or region-specific data on influenza-strain circulation, clinical outcomes and costs were obtained from published sources. The societal perspective was used and outcomes were expressed in International$ (I$) per quality-adjusted life-year (QALY) gained. RESULTS: When compared with TIV, we found that QIV would provide a greater reduction in influenza-related morbidity in communities in South Africa and Vietnam as compared with Australia. The incremental cost-effectiveness ratio of QIV versus TIV was estimated at I$4183/QALY in South Africa, I$1505/QALY in Vietnam and I$80,966/QALY in Australia. CONCLUSIONS: The cost-effectiveness of QIV varied between communities due to differences in influenza epidemiology, comorbidities, and unit costs. Whether TIV or QIV is the most cost-effective alternative heavily depends on influenza B burden among subpopulations targeted forvaccination in addition to country-specific willingness-to-pay thresholds and budgetary impact.

A systematic review of the health economic consequences of quadrivalent influenza vaccination.

BACKGROUND: Quadrivalent influenza vaccines (QIVs) contain antigens derived from an additional influenza type B virus as compared with currently used trivalent influenza vaccines (TIVs). This should overcome a potential reduced vaccine protection due to mismatches between TIV and circulating B viruses. In this study, we systematically reviewed the available literature on health economic evaluations of switching from TIV to QIV. Areas covered: The databases of Medline and Embase were searched systematically to identify health economic evaluations of QIV versus TIV published before September 2016.A total of sixteen studies were included, thirteen cost-effectiveness analyses and three cost-comparisons. Expert commentary: Published evidence on the cost-effectiveness of QIV suggests that switching from TIV to QIV would be a valuable intervention from both the public health and economic viewpoint. However, more research seems mandatory. Our main recommendations for future research include: 1) more extensive use of dynamic models in order to estimate the full impact of QIV on influenza transmission including indirect effects, 2) improved availability of data on disease outcomes and costs related to influenza type B viruses, and 3) more research on immunogenicity of natural influenza infection and vaccination, with emphasis on cross-reactivity between different influenza B viruses and duration of protection.

Economic Consequences and Potentially Preventable Costs Related to Osteoporosis in the Netherlands.

BACKGROUND: Osteoporosis often does not involve symptoms, and so the actual number of patients with osteoporosis is higher than the number of diagnosed individuals. This underdiagnosis results in a treatment gap. OBJECTIVES: To estimate the total health care resource use and costs related to osteoporosis in the Netherlands, explicitly including fractures, and to estimate the proportion of fracture costs that are linked to the treatment gap and might therefore be potentially preventable; to also formulate, on the basis of these findings, strategies to optimize osteoporosis care and treatment and reduce its related costs. METHODS: In this retrospective study, data of the Achmea Health Database representing 4.2 million Dutch inhabitants were used to investigate the economic consequence of osteoporosis in the Netherlands in 2010. Specific cohorts were created to identify osteoporosis-related fractures and their costs. Besides, costs of pharmaceutical treatment regarding osteoporosis were included. Using data from the literature, the treatment gap was estimated. Sensitivity analysis was performed on the base-case results. RESULTS: A total of 108,013 individuals with a history of fractures were included in this study. In this population, 59,193 patients were using anti-osteoporotic medication and 86,776 patients were using preventive supplements. A total number of 3,039 osteoporosis-related fractures occurred. The estimated total costs were €465 million. On the basis of data presented in the literature, the treatment gap in our study population was estimated to vary from 60% to 72%. CONCLUSIONS: The estimated total costs corrected for treatment gap were €1.15 to €1.64 billion. These results indicate room for improvement in the health care policy against osteoporosis.

The Effect of Individual Movements and Interventions on the Spread of Influenza in Long-Term Care Facilities.

BACKGROUND: Nosocomial influenza poses a serious risk among residents of long-term care facilities (LTCFs). OBJECTIVE: We sought to evaluate the effect of resident and staff movements and contact patterns on the outcomes of various intervention strategies for influenza control in an LTCF. METHODS: We collected contact frequency data in Canada's largest veterans' LTCF by enroling residents and staff into a study that tracked their movements through wireless tags and signal receivers. We analyzed and fitted the data to an agent-based simulation model of influenza infection, and performed Monte-Carlo simulations to evaluate the benefit of antiviral prophylaxis and patient isolation added to standard (baseline) infection control practice (i.e., vaccination of residents and staff, plus antiviral treatment of residents with symptomatic infection). RESULTS: We calibrated the model to attack rates of 20%, 40%, and 60% for the baseline scenario. For data-driven movements, we found that the largest reduction in attack rates (12.5% to 27%; ANOVA P < 0.001) was achieved when the baseline strategy was combined with antiviral prophylaxis for all residents for the duration of the outbreak. Isolation of residents with symptomatic infection resulted in little or no effect on the attack rates (2.3% to 4.2%; ANOVA P > 0.2) among residents. In contrast, parameterizing the model with random movements yielded different results, suggesting that the highest benefit was achieved through patient isolation (69.6% to 79.6%; ANOVA P < 0.001) while the additional benefit of prophylaxis was negligible in reducing the cumulative number of infections. CONCLUSIONS: Our study revealed a highly structured contact and movement patterns within the LTCF. Accounting for this structure-instead of assuming randomness-in decision analytic methods can result in substantially different predictions.

Cost-Effectiveness of Quadrivalent versus Trivalent Influenza Vaccine in the United States.

BACKGROUND: Designed to overcome influenza B mismatch, new quadrivalent influenza vaccines (QIVs) contain one additional B strain compared with trivalent influenza vaccines (TIVs). OBJECTIVE: To examine the expected public health impact, budget impact, and incremental cost-effectiveness of QIV versus TIV in the United States. METHODS: A dynamic transmission model was used to predict the annual incidence of influenza over the 20-year-period of 2014 to 2034 under either a TIV program or a QIV program. A decision tree model was interfaced with the transmission model to estimate the public health impact and the cost-effectiveness of replacing TIV with QIV from a societal perspective. Our models were informed by published data from the United States on influenza complication probabilities and relevant costs. The incremental vaccine price of QIV as compared with that of TIV was set at US $5.40 per dose. RESULTS: Over the next 20 years, replacing TIV with QIV may reduce the number of influenza B cases by 27.2% (16.0 million cases), resulting in the prevention of 137,600 hospitalizations and 16,100 deaths and a gain of 212,000 quality-adjusted life-years (QALYs). The net societal budget impact would be US $5.8 billion and the incremental cost-effectiveness ratio US $27,411/QALY gained. In the probabilistic sensitivity analysis, 100% and 96.5% of the simulations fell below US $100,000/QALY and US $50,000/QALY, respectively. CONCLUSIONS: Introducing QIV into the US immunization program may prevent a substantial number of hospitalizations and deaths. QIV is also expected to be a cost-effective alternative option to TIV.

Unremarked or Unperformed? Systematic Review on Reporting of Validation Efforts of Health Economic Decision Models in Seasonal Influenza and Early Breast Cancer.

BACKGROUND: Transparent reporting of validation efforts of health economic models give stakeholders better insight into the credibility of model outcomes. In this study we reviewed recently published studies on seasonal influenza and early breast cancer in order to gain insight into the reporting of model validation efforts in the overall health economic literature. METHODS: A literature search was performed in Pubmed and Embase to retrieve health economic modelling studies published between 2008 and 2014. Reporting on model validation was evaluated by checking for the word validation, and by using AdViSHE (Assessment of the Validation Status of Health Economic decision models), a tool containing a structured list of relevant items for validation. Additionally, we contacted corresponding authors to ask whether more validation efforts were performed other than those reported in the manuscripts. RESULTS: A total of 53 studies on seasonal influenza and 41 studies on early breast cancer were included in our review. The word validation was used in 16 studies (30 %) on seasonal influenza and 23 studies (56 %) on early breast cancer; however, in a minority of studies, this referred to a model validation technique. Fifty-seven percent of seasonal influenza studies and 71 % of early breast cancer studies reported one or more validation techniques. Cross-validation of study outcomes was found most often. A limited number of studies reported on model validation efforts, although good examples were identified. Author comments indicated that more validation techniques were performed than those reported in the manuscripts. CONCLUSIONS: Although validation is deemed important by many researchers, this is not reflected in the reporting habits of health economic modelling studies. Systematic reporting of validation efforts would be desirable to further enhance decision makers' confidence in health economic models and their outcomes.

Retrospective public health impact of a quadrivalent influenza vaccine in the United States.

INTRODUCTION: Vaccination is an effective preventive strategy against influenza. However, current trivalent influenza vaccines (TIVs) contain only one of the two influenza B lineages that circulate each year. Vaccine mismatches are frequent because predicting which one will predominate is difficult. Recently licensed quadrivalent influenza vaccines (QIVs) containing the two B lineages should address this issue. Our study estimates their impact by assessing what would have been the US public health benefit of routinely vaccinating with QIV in 2000-2013. METHODS: We developed a dynamic compartmental model that accounts for interactions between influenza B lineages (natural or vaccine-induced) and simulates the multiyear influenza dynamics for 2000-2013. Age-structured population dynamics, vaccine efficacy (VE) per strain, and weekly ramp-up of vaccination coverage are modeled. Sensitivity analyses were performed on VE, duration of immunity, and levels of vaccine-induced cross-protection between B lineages. RESULTS: Assuming a cross-protection of 70% of the VE of the matched vaccine, the model predicts 16% more B lineage cases prevented by QIV. Elderly (≥65 years) and young seniors (50-64 years) benefit most from QIV, with 21% and 18% reductions in B lineage cases. Reducing cross-protection to 50%, 30%, and 0% of the VE of the matched vaccine improves the relative benefit of QIV to 25%, 30%, and 34% less B lineage cases. CONCLUSION: Using a dynamic retrospective framework with real-life vaccine mismatch, our analysis shows that QIV routine vaccination in the United States has the potential to substantially reduce the number of influenza infections, even with relatively high estimates of TIV-induced cross-protection.