Lifecycle model-based evaluation of infant 4CMenB vaccination in the UK.

OBJECTIVES: Invasive meningococcal disease, an uncommon but severe disease, imposes catastrophic health and economic burdens. Cost-utility analysis (CUA) assumes separability in lifetime health and economic variables and cannot capture the full value of preventing such burdens. We overcome these limitations with a retrospective societal perspective cost-benefit analysis (CBA) of meningococcal serogroup B vaccination (4CMenB) of one infant cohort in the United Kingdom using a health-augmented lifecycle model (HALM) incorporating health's interactions with consumption, earnings, non-market time and financial risk. METHODS: We used a static Markov model of vaccination's health impact and an HALM to estimate the private willingness to pay (PWTP) for the intrinsic and instrumental value of health under perfect capital markets, financial risk protection in the absence of insurance against permanent disability, parental spillovers, and acute phase disability. We estimated social WTP (SWTP) incorporating social severity preferences. We estimated rates of return that inform health payer reimbursement decisions, finance ministry budgeting decisions, and legislature taxation decisions. An expert Advisory Board investigated the validity of applying the HALM to infant 4CMenB. RESULTS: The PWTP for a 2 + 1 vaccination schedule is £395, comprising £166 of disability insurance value, £79 of positive parental spillover value, £28 in the value of averting acute phase disability, and £122 in residual intrinsic and instrumental value of health. SWTP is £969. CONCLUSIONS: HALM-based CBA provides an empirically richer, more utility-theoretically grounded approach to vaccine evaluation than CUA, demonstrating good value for money for legislatures (based on private values) and for all decision-makers (based on social values).

COVID-19 vaccines should be evaluated from the societal perspective.

The COVID-19 pandemic demonstrates the importance of valuing vaccines from a broad societal perspective (SP), as opposed to a narrower health-payer perspective (HPP). COVID-19's catastrophic global impacts extend not only to its health-related effects, but also to the profound macroeconomic losses caused by lockdowns required for disease control, leading to the worst global economic crisis in a century. COVID-19 vaccination (CV) has been the central policy tool for resolving this economic crisis, and it has been hypothesized that this macroeconomic benefit alone justifies the cost of CV many times over. Yet HPP-based vaccine valuations are wholly insensitive to this enormous benefit, not allowing it to influence the allocation of given health budgets nor the determination of the magnitudes of such budgets, thereby risking inadequate societal spending on CV. HPP allocates given health budgets to maximize only health, giving no weight to macroeconomic outcomes, causing allocative inefficiency by not allowing welfare-improving trade-offs of health for wealth. HPP assumes health budgets are optimal, not scrutinizing whether their scale adequately reflects the macroeconomic benefits of health spending, thereby risking productive inefficiency by foregoing health spending increases such as on CV that could raise both population-level health and wealth. These allocative and productive inefficiencies in turn distort for-profit R&D incentives, risking dynamic inefficiency. And since the socio-economic and health burdens of COVID-19 are disproportionately borne by the worse off, HPP's failure to promote optimal levels of societal investment in CV may disproportionately burden the worse off as well, exacerbating inequality. Vaccine valuations from the societal perspective allow the allocation and determination of health budgets to reflect macroeconomic and distributional values, thereby promoting allocative, productive, and dynamic efficiency, as well as equity. These considerations of efficiency and equity support evaluating CV, and to ensure a level playing field, all vaccines, from a societal perspective.

Immunization, not vaccination: monoclonal antibodies for infant RSV prevention and the US vaccines for children program.

In the US, RSV imposes significant burdens on infants, households, and the health system. Yet the only licensed immunization is accessible to only certain risk groups comprising 2% of the infant population, leaving the remaining 98% unprotected. An effective immunization for all infants is a significant public health priority. One possible solution is the FDA-approved monoclonal antibody nirsevimab, which recent evidence suggests is safe and effective in preventing RSV in all infants, and which is currently being considered for inclusion in the pediatric immunization schedule and the federal Vaccines for Children (VFC) program. But the question arises whether passive immunization products like nirsevimab ought to be eligible for the VFC, which nominally and traditionally centers on vaccines providing active immunity. Addressing this is urgent because VFC inclusion will be decided on imminently. I argue there are strong policy grounds, i.e., reasons grounded in the ultimate health system goals of maximizing population health or social welfare subject to resource constraints, not to exclude passive immunization from VFC eligibility. Active and passive immunizations both provide adaptive immunity and can therefore produce qualitatively similar effects on risks of infection, disease, and transmission; on disease severity and duration; and on health, welfare, and health resource use. The distinction between active and passive immunization does not intrinsically matter since what matters for the attainment of health system goals is the extent of immunity conferred, not whether immunity is active or passive. Nor can passivity be considered a useful proxy for conferring a lesser extent of immunity, since no such proxy is needed (existing valuation methods can cope with variations in product attributes), and it is a poor proxy (passive immunizations can be better for individuals with impaired immune systems and can have comparable effectiveness durations and economic value as vaccines).

The value of vaccines.

Optimizing vaccine spending depends on recognizing the full value of vaccination (VoV). Existing taxonomies of such value are not comprehensive because they are not guided by general theories. I rely on two such theories: subjective-value theory claims that what has value is determined by what people actually or ideally want in life. A welfarist theory of government states that a fundamental objective of government is to promote social value (or social welfare). These jointly imply that any aspect of life that individuals actually or ideally value and that could be negatively affected by vaccine-preventable diseases (and therefore positively affected by preventive vaccines) is an element of VoV. I build a more comprehensive-value taxonomy than currently exists based on this implication.

Cost-utility and cost-benefit analysis of pediatric PCV programs in Egypt.

New vaccine introductions (NVIs) raise issues of value for money (VfM) for self-financing middle-income countries like Egypt. We evaluate a pediatric pneumococcal conjugate vaccine (PCV) NVI in Egypt from health payer and societal perspectives, using cost-utility and cost-benefit analysis (CUA, CBA). We evaluate vaccinating 100 successive birth cohorts with the 13-valent PCV ("PCV13") and the 10-valent PCV ("PCV10") relative to no vaccination and each other. We quantify health effects with a disease incidence projection model and a multiple-cohort static disease model. Our CBA uses a health-augmented lifecycle model to generate willingness-to-pay for health gains from which we calculate rates of return (RoR). We obtain parameters from the published literature. We perform deterministic and probabilistic sensitivity analysis. Our base-case CUA finds incremental cost-effectiveness ratios (ICERs) for PCV13 and PCV10 relative to no program of $926 (95% confidence interval $512-$1,735) and $1,984 ($1,186-$3,805) per quality-adjusted life year (QALY), respectively; and for PCV13 relative to PCV10 of $174 ($88-$331) per QALY. Our base-case CBA finds RoRs to PCV13 and PCV10 relative to no program of 488% (188-993%) and 164% (33-336%), respectively, and to PCV13 relative to PCV10 of 3109% (1410-6602%). Both CUA and CBA find PCV13 to be good VfM relative to PCV10.

Cost-utility and cost-benefit analysis of TAVR availability in the US severe symptomatic aortic stenosis patient population.

AIMS: We evaluated the availability of transcatheter aortic valve replacement (TAVR) to determine its value across all severe symptomatic aortic stenosis (SSAS) patients, especially those untreated because of concerns regarding invasive surgical AVR (SAVR) and its impact on active aging. METHODS: We performed payer perspective cost-utility analysis (CUA) and societal perspective cost-benefit analysis (CBA). The CBA's benefit measure is active time: salaried labor, unpaid work, and active leisure. The study population is a cohort of US elderly SSAS patients. We compared a "TAVR available" scenario in which SSAS patients distribute themselves across TAVR, SAVR, and medical management (MM); and a "TAVR not available" scenario with only SAVR and MM. We structured each scenario with a decision-tree model of SSAS patient treatment allocation. We measured the association between health and active time in the US Health and Retirement Study and used this association to impute active time to SSAS patients given their health. RESULTS: The incremental cost-effectiveness ratio (ICER) and rate of return (RoR) of TAVR availability were $8,533 and 395%, respectively. CUA net monetary benefits (NMB) were $212,199 per patient and $43.4 billion population-wide. CBA NMB were $50,530 per patient and $10.3 billion population-wide. LIMITATIONS: Among study limitations were scarcity of evidence regarding key parameters and the lack of long-term survival, health utility, and treatment cost data. Our analysis did not account for TAVR durability, retreatments, and valve-in-valve treatments. CONCLUSION: Across risk-, age-, and treatment-eligibility groups, TAVR is the economically optimal treatment choice. It represents strong value-for-money per patient and population-wide. The vast majority of TAVR value involves raising treatment uptake among the untreated.

Aortic stenosis (AS) is a common and lethal heart disease. Surgical treatment has long been available, but its invasiveness limits uptake. More recently, transcatheter aortic valve replacement (TAVR) has emerged as a treatment alternative. Its minimal invasiveness has significantly increased treatment rates, but economic evaluations omit this benefit, risking undervaluation. We evaluated TAVR in elderly US severe symptomatic AS patients, using payer perspective cost-utility analysis (CUA) and societal perspective cost-benefit analysis (CBA). Both CUA and CBA incorporated TAVR's impact on treatment rates. Given patient preferences for treatment options promoting active aging, our CBA used the value of active time as a benefit measure. We found that CUA/CBA net monetary benefits are $212,199/$50,530 per patient. Across risk-, age-, and treatment-eligibility groups, TAVR is the economically optimal treatment choice over surgery and medical management. It represents strong value-for-money per patient and population-wide. Increased treatment uptake accounts for the vast share of TAVR's value.

Indirect costs of adult pneumococcal disease and the productivity-based rate of return to the 13-valent pneumococcal conjugate vaccine for adults in Turkey.

Productivity benefits of health technologies are ignored in typical economic evaluations from a health payer's perspective, risking undervaluation. We conduct a productivity-based cost-benefit analysis from a societal perspective and estimate indirect costs of adult pneumococcal disease, vaccination benefits from the adult 13-valent pneumococcal conjugate vaccine (PCV13 Adult), and rates of return to PCV13 Adult for a range of hypothetical vaccination costs. Our context is Turkey's funding PCV13 for the elderly and for non-elderly adults with select comorbidities within the Ministry of Health's National Immunization Program. We use a Markov model with one-year cycles. Indirect costs from death or disability equal the expected present discounted value of lifetime losses in the infected individual's paid and unpaid work and in caregivers' paid work. Vaccination benefits comprise averted indirect costs. Rates of return equal vaccination benefits divided by vaccination costs, minus one. Input parameters are from public data sources. We model comorbidities' effects by scalar multiplication of the parameters of the general population. Indirect costs per treatment episode of inpatient community-acquired pneumonia (CAP), bacteremia, and meningitis - but not for outpatient CAP - approach or exceed Turkish per capita gross domestic product. Vaccination benefits equal $207.02 per vaccination in 2017 US dollars. The rate of return is positive for all hypothetical costs below this. Results are sensitive to herd effects from pediatric vaccination and vaccine efficacy rates. For a wide range of hypothetical vaccination costs, the rate of return compares favorably with those of other global development interventions with well-established strong investment cases.

Toward economic evaluation of the value of vaccines and other health technologies in addressing AMR.

We discuss the need to make economic evaluations of vaccines antimicrobial resistance (AMR)-sensitive and ways to do so. Such AMR-sensitive evaluations can play a role in value-for-money comparisons of different vaccines within a national immunization program, or in comparisons of vaccine-centric and non-vaccine-centric technologies within an anti-AMR program. In general terms, incremental cost-effectiveness ratios and rates of return and their associated decision rules are unaltered by consideration of AMR-related value. The decision metrics need to have their various health, cost, and socioeconomic terms disaggregated into resistance-related subcategories, which in turn have to be measured carefully before they are reaggregated. The fundamental scientific challenges lie primarily in quantifying the causal impact of health technologies on resistance-related health outcomes, and secondarily in ascertaining the economic value of those outcomes. We emphasize the importance of evaluating vaccines in the context of other potentially complementary and substitutable nonvaccine technologies. Complementarity implies that optimal spending on each set of interventions is positive, and substitutability implies that the ratio of spending will depend on relative value for money. We exemplify this general point through a qualitative discussion of the complementarities and (especially the) substitutability between pneumococcal conjugate vaccines and antimicrobial stewardship and between research and development (R&D) of a gonorrhea vaccine versus R&D of a gonorrhea antibiotic. We propose a roadmap for future work, which includes quantifying the causal effects of vaccination and other health technologies on short-term and long-term resistance-related outcomes, measuring the health-sector costs and broader socioeconomic consequences of resistance-related mortality and morbidity, and evaluating vaccines in the context of nonvaccine complements and substitutes.

MCDA or preference-based social welfare functions?

Preference-based social welfare functions (pbSWF) perform better at reconciling competing personal and social goals than typical forms of MCDA. Its virtues are (a) its respect for people's own judgments about the relative values of health, wealth, and other broad benefits within their lives (non-paternalism) and (b) its conformity with reasonable ethical axioms. Any discrepancy between an MCDA objective function and that implied by pbSWF suggests the former's failure to respect non-paternalism and reasonable ethical principles. The pbSWF approach is implementable using micro-econometric evidence on personal preferences over health, wealth, and other broad benefits; and surveys of the general population or their representatives to ascertain the social acceptability of certain ethical axioms and the degree of inequality aversion.

The broad socioeconomic benefits of vaccination.

Evaluating vaccination programs according to their broad socioeconomic benefits, beyond their health benefits, will help to address the twin problems of vaccine underutilization and weak incentives for vaccine innovation.