Economic evaluation of influenza pandemic mitigation strategies in the United States using a stochastic microsimulation transmission model
Sander, B., Nizam, A., Garrison Jr., L.P., (...), Halloran, M.E., Longini Jr., I.M.
Value in Health. 2009;12(2):80
OBJECTIVES
To project the potential economic impact of pandemic influenza mitigation strategies from a societal perspective in the United States.
METHODS
We use a stochastic agent-based model to simulate pandemic influenza in the community. We compare 17 strategies: targeted antiviral prophylaxis (TAP) alone and in combination with school closure as well as prevaccination.
RESULTS
In the absence of intervention, we predict a 50% attack rate with an economic impact of $187 per capita as loss to society. Full TAP (FTAP) is the most effective single strategy, reducing number of cases by 54% at the lowest cost to society ($127 per capita). Prevaccination reduces number of cases by 48% and is the second least costly alternative ($140 per capita). Adding school closure to FTAP or prevaccination further improves health outcomes but increases total cost to society by approximately $2700 per capita.
CONCLUSION
FTAP is an effective and cost-saving measure for mitigating pandemic influenza.
Cost-Effectiveness of Quadrivalent versus Trivalent Influenza Vaccine in the United States
de Boer P.T., Crépey P., Pitman R.J., Macabeo B., Chit A., Postma M.J.
Value in Health. 2016;19(8):12.
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.
Modeling the Effects of H1N1 Influenza Vaccine Distribution in the United States
Larson R.C., Teytelman A.
Value in Health. 2012;15(1):9.
OBJECTIVE
We analyzed the effects of the timing of vaccine distribution in 11 US states during the 2009 H1N1 influenza pandemic.
METHODS
By using reported data on the fraction of patients presenting with flu-related symptoms, we developed a transformation that allowed estimation of the state-specific temporal flu wave curve, representing the number of new infections during each week. We also utilized data describing the weekly numbers of vaccine doses delivered and administered. By using a simple difference equations model of flu progression, we developed two influenza wave curves: first, an “observable” curve that included the beneficial effects of vaccinations, and second, an unobservable curve that depicted how the flu would have progressed with no vaccine administered. We fit the observable curve to match the estimated epidemic curve and early exponential growth associated with R , the reproductive number. By comparing the number of infections in each scenario, we estimated the infections averted by the administration of vaccine.
RESULTS
Southern states experienced peak infection several weeks before northern states, and most of the vaccine was delivered well after the peak of the southern flu wave. Our models suggest that the vaccine had minimal ameliorative impact in the southern states and measurable positive impact in the northern states. Vaccine delivery after peak also results in a smaller fraction of the population's seeking the vaccine.
CONCLUSION
Our analysis suggests that current Centers for Disease Control and Prevention policy of allocating flu vaccine over time in direct proportion to states' populations may not be best in terms of averting nationally the maximum possible number of infections.
Reliability, Validity, and Responsiveness of InFLUenza Patient-Reported Outcome (FLU-PRO©) Scores in Influenza-Positive Patients
Powers, J.H., Bacci, E.D., Guerrero, M.L., (...), Dugas, A., Ruiz-Palacios, G.M.
Value in Health. 2018;21(2):6.
To assess the reliability, validity, and responsiveness of InFLUenza Patient-Reported Outcome (FLU-PRO©) scores for quantifying the presence and severity of influenza symptoms.
METHODS
An observational prospective cohort study of adults (≥18 years) with influenza-like illness in the United States, the United Kingdom, Mexico, and South America was conducted. Participants completed the 37-item draft FLU-PRO daily for up to 14 days. Item-level and factor analyses were used to remove items and determine factor structure. Reliability of the final tool was estimated using Cronbach α and intraclass correlation coefficients (2-day reliability). Convergent and known-groups validity and responsiveness were assessed using global assessments of influenza severity and return to usual health.
RESULTS
Of the 536 patients enrolled, 221 influenza-positive subjects comprised the analytical sample. The mean age of the patients was 40.7 years, 60.2% were women, and 59.7% were white. The final 32-item measure has six factors/domains (nose, throat, eyes, chest/respiratory, gastrointestinal, and body/systemic), with a higher order factor representing symptom severity overall (comparative fit index = 0.92; root mean square error of approximation = 0.06). Cronbach α was high (total = 0.92; domain range = 0.71–0.87); test-retest reliability (intraclass correlation coefficient, day 1–day 2) was 0.83 for total scores and 0.57 to 0.79 for domains. Day 1 FLU-PRO domain and total scores were moderately to highly correlated (≥0.30) with Patient Global Rating of Flu Severity (except nose and throat). Consistent with known-groups validity, scores differentiated severity groups on the basis of global rating (total: F = 57.2, P 0.05) FLU-PRO score improvement by day 7 than did those who did not, suggesting score responsiveness.
CONCLUSIONS
Results suggest that FLU-PRO scores are reliable, valid, and responsive to change in influenza-positive adults.
Model Comparisons of the Effectiveness and Cost-Effectiveness of Vaccination- A Systematic Review of the Literature
Drolet M., Bénard É., Jit M., Hutubessy R., Brisson M.
Value in Health. 2018;21(10):5.
To describe all published articles that have conducted comparisons of model-based effectiveness and cost-effectiveness results in the field of vaccination. Specific objectives were to 1) describe the methodologies used and 2) identify the strengths and limitations of the studies.
METHODS
We systematically searched MEDLINE and Embase databases for studies that compared predictions of effectiveness and cost-effectiveness of vaccination of two or more mathematical models. We categorized studies into two groups on the basis of their data source for comparison (previously published results or new simulation results) and performed a qualitative synthesis of study conclusions.
RESULTS
We identified 115 eligible articles (only 5% generated new simulations from the reviewed models) examining the effectiveness and cost-effectiveness of vaccination against 14 pathogens (69% of studies examined human papillomavirus, influenza, and/or pneumococcal vaccines). The goal of most of studies was to summarize evidence for vaccination policy decisions, and cost-effectiveness was the most frequent outcome examined. Only 33%, 25%, and 3% of studies followed a systematic approach to identify eligible studies, assessed the quality of studies, and performed a quantitative synthesis of results, respectively. A greater proportion of model comparisons using published studies followed a systematic approach to identify eligible studies and to assess their quality, whereas more studies using new simulations performed quantitative synthesis of results and identified drivers of model conclusions. Most comparative modeling studies concluded that vaccination was cost-effective.
CONCLUSIONS
Given the variability in methods used to conduct/report comparative modeling studies, guidelines are required to enhance their quality and transparency and to provide better tools for decision making.
Value for Money in H1N1 Influenza- A Systematic Review of the Cost-Effectiveness of Pandemic Interventions
Pasquini-Descomps H., Brender N., Maradan D.
Value in Health. 2017;20(6):2.
BACKGROUND
The 2009 A/H1N1 influenza pandemic generated additional data and triggered new studies that opened debate over the optimal strategy for handling a pandemic. The lessons-learned documents from the World Health Organization show the need for a cost estimation of the pandemic response during the risk-assessment phase. Several years after the crisis, what conclusions can we draw from this field of research?
OBJECTIVES
The main objective of this article was to provide an analysis of the studies that present cost-effectiveness or cost-benefit analyses for A/H1N1 pandemic interventions since 2009 and to identify which measures seem most cost-effective.
METHODS
We reviewed 18 academic articles that provide cost-effectiveness or cost-benefit analyses for A/H1N1 pandemic interventions since 2009. Our review converts the studies’ results into a cost-utility measure (cost per disability-adjusted life-year or quality-adjusted life-year) and presents the contexts of severity and fatality.
RESULTS
The existing studies suggest that hospital quarantine, vaccination, and usage of the antiviral stockpile are highly cost-effective, even for mild pandemics. However, school closures, antiviral treatments, and social distancing may not qualify as efficient measures, for a virus like 2009’s H1N1 and a willingness-to-pay threshold of $45,000 per disability-adjusted life-year. Such interventions may become cost-effective for severe crises.
CONCLUSIONS
This study helps to shed light on the cost-utility of various interventions, and may support decision making, among other criteria, for future pandemics. Nonetheless, one should consider these results carefully, considering these may not apply to a specific crisis or country, and a dedicated cost-effectiveness assessment should be conducted at the time.
Cost-Effectiveness Analysis for Influenza Vaccination Coverage and Timing in Tropical and Subtropical Climate Settings: A Modeling Study
Yue, M., Dickens, B.L., Yoong, J.S.-Y., (...), Teerawattananon, Y., Cook, A.R.
Value in Health. 2019;22(12):1.
BACKGROUND
The lack of seasonality in influenza epidemics in the tropics makes the application of well-established temperate zone national vaccination plans challenging.
OBJECTIVES
We developed an individual-based simulation model to study optimal vaccination scheduling and assess cost-effectiveness of these vaccination schedules in scenarios of no influenza seasonality and the seasonality regimes of Singapore, Taipei, and Tokyo.
METHODS
The simulation models heterogeneities in human contact networks, levels of protective antibodies following infection, the effectiveness of the influenza vaccine, and seasonality. Using a no intervention baseline, we consider 3 alternative vaccination strategies: (1) annual vaccination for a percentage of the elderly, (2) biannual vaccination for a percentage of the elderly, and (3) annual vaccination for all elderly and a fraction of the remaining population. We considered 5 vaccination uptake rates for each strategy and modeled the estimated costs, quality-adjusted life years, and incremental cost-effectiveness ratios (ICERs), indicating the cost-effectiveness of each scenario.
RESULTS
In Singapore, annual vaccination for a proportion of elderly is largely cost-effective. However, with fixed uptake rates, partial biannual vaccination for the elderly yields a higher ICER than partial annual vaccination for the elderly, resulting in a cost-ineffective ICER. The most optimal strategy is the total vaccination of all the elderly and a proportion of individuals from other age groups, which results in a cost-saving ICER. This finding is consistent across different seasonality regimes.
CONCLUSIONS
Tropical countries like Singapore can have comparably cost-effective vaccination strategies as found in countries with winter epidemics. The vaccination of all the elderly and a proportion of other age groups is the most cost-effective strategy, supporting the need for an extensive national influenza vaccination program.
A Scoping Review of Investment Cases for Vaccines and Immunization Programs
Sim S.Y., Jit M., Constenla D., Peters D.H., Hutubessy R.C.W.
Value in Health. 2019;22(8):0.
BACKGROUND
Many investment cases have recently been published intending to show the value of new health investments, but without consistent methodological approaches.
OBJECTIVES
To conduct a scoping review of existing investment cases (using vaccines and immunization programs as an example), identify common characteristics that define these investment cases, and examine their role within the broader context of the vaccine development and introduction.
METHODS
A systematic search was conducted from January 1980 to November 2017 to identify investment cases in the area of vaccines and immunization programs from gray literature and electronic bibliographic databases. Investment case outcomes, objectives, key variables, target audiences, and funding sources were extracted and analyzed according to their reporting frequency.
RESULTS
We found 24 investment cases, and most of them aim to provide information for decisions (12 cases) or advocate for a specific agenda (9 cases). Outcomes presented fell into 4 broad categories—burden of disease, cost of investment, impact of investment, and other considerations for implementation. Number of deaths averted (70%), incremental cost-effectiveness ratios (67%), and reduction in health and socioeconomic inequalities (54%) were the most frequently reported outcome measures for impact of investment. Health system capacity (79%) and vaccine financing landscape (75%) were the most common considerations for implementation. A sizable proportion (41.4%) of investment cases did not reveal their funding sources.
CONCLUSIONS
This review describes information that is critical to decision making about resource mobilization and allocation concerning vaccines. Global efforts to harmonize investment cases more broadly will increase transparency and comparability.
Evaluation of Efficacy Endpoints for a Phase IIb Study of a Respiratory Syncytial Virus Vaccine in Older Adults Using Patient-Reported Outcomes With Laboratory Confirmation
Yu, J., Powers, J.H., Vallo, D., Falloon, J.
Value in Health. 2020;23(2):0.
OBJECTIVES
There are no approved vaccines for respiratory syncytial virus (RSV), and consensus on methods to assess RSV vaccine efficacy has not been established. In this study of an adjuvanted RSV vaccine, we evaluated an RSV disease endpoint using a patient-reported outcome instrument (the inFLUenza Patient-Reported Outcome instrument [FLU-PRO]) and molecular testing for virologic confirmation.
METHODS
In a randomized, blinded efficacy study (NCT02508194), 1900 adult participants aged ≥60 years who had any respiratory symptom lasting ≥24 hours recorded symptoms in a FLU-PRO–based workbook for 21 days, self-collected nasal swabs on illness days 2 to 4, and had a site-collected swab obtained on (approximately) day 4. The endpoint, acute RSV-associated respiratory illness (ARA-RI), required specific symptoms with virologic confirmation.
RESULTS
The FLU-PRO demonstrated reliability, ability to detect change, and validity and had high participant adherence and acceptable patient burden in the setting of an RSV prevention trial. The ARA-RI endpoint definition captured all 33 virologically confirmed RSV illnesses for which symptom data were provided, and in 32 of these, at least 1 lower respiratory symptom was reported. Sensitivity analysis with an endpoint requiring ≥2 lower respiratory symptoms captured greater symptom severity but fewer cases. Results of self- and site-collected swabs were highly correlated. Self-swabbing detected 9 additional cases that would have been missed by site swabbing only.
CONCLUSIONS
These results demonstrated the reliability and validity of the ARA-RI definition and of the FLU-PRO for use in RSV studies. Self-swabbing improved RSV detection.
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