The economic case for scaling up health research and development: Lessons from the COVID-19 pandemic.

In response to the COVID-19 pandemic, governments directly funded vaccine research and development (R&D), quickly leading to multiple effective vaccines and resulting in enormous health and economic benefits to society. We develop a simple economic model showing this feat could potentially be repeated for other health challenges. Based on inputs from the economic and medical literatures, the model yields estimates of optimal R&D spending on treatments and vaccines for known diseases. Taking a global and societal perspective, we estimate the social benefits of such spending and a corresponding rate of return. Applications to Streptococcus A vaccines and Alzheimer's disease treatments demonstrate the potential of enhanced research and development funding to unlock massive global health and health-related benefits. We estimate that these benefits range from 2 to 60 trillion (2020 US$) and that the corresponding rates of return on R&D spending range from 12% to 23% per year for 30 y. We discuss the current shortfall in R&D spending and public policies that can move current funding closer to the optimal level.

Transforming vaccine development.

The urgency to develop vaccines against Covid-19 is putting pressure on the long and expensive development timelines that are normally required for development of lifesaving vaccines. There is a unique opportunity to take advantage of new technologies, the smart and flexible design of clinical trials, and evolving regulatory science to speed up vaccine development against Covid-19 and transform vaccine development altogether.

Health and Economic Growth: Reconciling the Micro and Macro Evidence.

Economists use micro-based and macro-based approaches to assess the macroeconomic return to population health. The macro-based approach tends to yield estimates that are either negative and close to zero or positive and an order of magnitude larger than the range of estimates derived from the micro-based approach. This presents a micro-macro puzzle regarding the macroeconomic return to health. We reconcile the two approaches by controlling for the indirect effects of health on income per capita, which macro-based approaches usually include but micro-based approaches deliberately omit when isolating the direct income effects of health. Our results show that the macroeconomic return to health lies in the range of plausible microeconomic estimates, demonstrating that both approaches are in fact consistent with one another.

Cohort Profile: Real-Time Insights of COVID-19 in India (RTI COVID-India).

BACKGROUND: The coronavirus disease (COVID) pandemic caused disruption globally and was particularly distressing in low- and middle-income countries such as India. This study aimed to provide population representative estimates of COVID-related outcomes in India over time and characterize how COVID-related changes and impacts differ by key socioeconomic groups across the life course. METHODS: The sample was leveraged from an existing nationally representative study on cognition and dementia in India: Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD). The wave-1 of LASI-DAD enrolled 4096 older adults aged 60 years and older in 3316 households from 18 states and union territories of India. Out of the 3316 LASI-DAD households, 2704 with valid phone numbers were contacted and invited to participate in the Real-Time Insights COVID-19 in India (RTI COVID-India) study. RTI COVID-India was a bi-monthly phone survey that provided insight into the individual's knowledge, attitudes, and behaviour towards COVID-19 and changes in the household's economic and health conditions throughout the pandemic. The survey was started in May 2020 and 9 rounds of data have been collected. FINDINGS TILL DATE: Out of the 2704 LASI-DAD households with valid phone numbers, 1766 households participated in the RTI COVID-India survey at least once. Participants were in the age range of 18-102 years, 49% were female, 66% resided in rural area. Across all rounds, there was a higher report of infection among respondents aged 60-69 years. There was a greater prevalence of COVID-19 diagnosis reported in urban (23.0%) compared to rural areas (9.8%). Respondents with higher education had a greater prevalence of COVID-19 diagnosis compared to those with lower or no formal education. Highest prevalence of COVID-19 diagnosis was reported from high economic status compared to middle and low economic status households. Comparing education gradients in experiencing COVID-19 symptoms and being diagnosed, we observe an opposite pattern: respondents with no formal schooling reported the highest level of experiencing COVID-19 symptoms, whereas the greatest proportion of the respondents with secondary school or higher education reported being diagnosed with COVID-19. FUTURE PLANS: The study group will analyse the data collected showing the real-time changes throughout the pandemic and will make the data widely available for researchers to conduct further studies.

The benefits and costs of U.S. employer COVID-19 vaccine mandates.

In 2021, the Biden Administration issued mandates requiring COVID-19 vaccinations for U.S. federal employees and contractors and for some healthcare and private sector workers. These mandates have been challenged in court; some have been halted or delayed. However, their costs and benefits have not been rigorously appraised. This study helps fill that gap. We estimate the direct costs and health-related benefits that would have accrued if these vaccination requirements had been implemented as intended. Compared with the January 2022 vaccination rates, we find that the mandates could have led to 15 million additional vaccinated individuals, increasing the overall proportion of the fully vaccinated U.S. population from 64% to 68%. The associated net benefits depend on the subsequent evolution of the pandemic-information unavailable ex ante to analysts or policymakers. In scenarios involving the emergence of a novel, more transmissible variant, against which vaccination and previous infection offer moderate protection, the estimated net benefits are potentially large. They reach almost $20,000 per additional vaccinated individual, with more than 20,000 total deaths averted over the 6-month period assessed. In scenarios involving a fading pandemic, existing vaccination-acquired or infection-acquired immunity provides sufficient protection, and the mandates' benefits are unlikely to exceed their costs. Thus, mandates may be most useful when the consequences of inaction are catastrophic. However, we do not compare the effects of mandates with alternative policies for increasing vaccination rates or for promoting other protective measures, which may receive stronger public support and be less likely to be overturned by litigation.

Prevalence of dementia in India: National and state estimates from a nationwide study.

INTRODUCTION: Prior estimates of dementia prevalence in India were based on samples from selected communities, inadequately representing the national and state populations. METHODS: From the Longitudinal Aging Study in India (LASI) we recruited a sample of adults ages 60+ and administered a rich battery of neuropsychological tests and an informant interview in 2018 through 2020. We obtained a clinical consensus rating of dementia status for a subsample (N = 2528), fitted a logistic model for dementia status on this subsample, and then imputed dementia status for all other LASI respondents aged 60+ (N = 28,949). RESULTS: The estimated dementia prevalence for adults ages 60+ in India is 7.4%, with significant age and education gradients, sex and urban/rural differences, and cross-state variation. DISCUSSION: An estimated 8.8 million Indians older than 60 years have dementia. The burden of dementia cases is unevenly distributed across states and subpopulations and may therefore require different levels of local planning and support. HIGHLIGHTS: The estimated dementia prevalence for adults ages 60+ in India is 7.4%. About 8.8 million Indians older than 60 years live with dementia. Dementia is more prevalent among females than males and in rural than urban areas. Significant cross-state variation exists in dementia prevalence.

Hypertension awareness, treatment, and control and their association with healthcare access in the middle-aged and older Indian population: A nationwide cohort study.

BACKGROUND: Hypertension is the most important cardiovascular risk factor in India, and representative studies of middle-aged and older Indian adults have been lacking. Our objectives were to estimate the proportions of hypertensive adults who had been diagnosed, took antihypertensive medication, and achieved control in the middle-aged and older Indian population and to investigate the association between access to healthcare and hypertension management. METHODS AND FINDINGS: We designed a nationally representative cohort study of the middle-aged and older Indian population, the Longitudinal Aging Study in India (LASI), and analyzed data from the 2017-2019 baseline wave (N = 72,262) and the 2010 pilot wave (N = 1,683). Hypertension was defined as self-reported physician diagnosis or elevated blood pressure (BP) on measurement, defined as systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg. Among hypertensive individuals, awareness, treatment, and control were defined based on self-reports of having been diagnosed, taking antihypertensive medication, and not having elevated BP, respectively. The estimated prevalence of hypertension for the Indian population aged 45 years and older was 45.9% (95% CI 45.4%-46.5%). Among hypertensive individuals, 55.7% (95% CI 54.9%-56.5%) had been diagnosed, 38.9% (95% CI 38.1%-39.6%) took antihypertensive medication, and 31.7% (95% CI 31.0%-32.4%) achieved BP control. In multivariable logistic regression models, access to public healthcare was a key predictor of hypertension treatment (odds ratio [OR] = 1.35, 95% CI 1.14-1.60, p = 0.001), especially in the most economically disadvantaged group (OR of the interaction for middle economic status = 0.76, 95% CI 0.61-0.94, p = 0.013; OR of the interaction for high economic status = 0.84, 95% CI 0.68-1.05, p = 0.124). Having health insurance was not associated with improved hypertension awareness among those with low economic status (OR = 0.96, 95% CI 0.86-1.07, p = 0.437) and those with middle economic status (OR of the interaction = 1.15, 95% CI 1.00-1.33, p = 0.051), but it was among those with high economic status (OR of the interaction = 1.28, 95% CI 1.10-1.48, p = 0.001). Comparing hypertension awareness, treatment, and control rates in the 4 pilot states, we found statistically significant (p < 0.001) improvement in hypertension management from 2010 to 2017-2019. The limitations of this study include the pilot sample being relatively small and that it recruited from only 4 states. CONCLUSIONS: Although considerable variations in hypertension diagnosis, treatment, and control exist across different sociodemographic groups and geographic areas, reducing uncontrolled hypertension remains a public health priority in India. Access to healthcare is closely tied to both hypertension diagnosis and treatment.

Social determinants of mortality from COVID-19: A simulation study using NHANES.

BACKGROUND: The COVID-19 epidemic in the United States is widespread, with more than 200,000 deaths reported as of September 23, 2020. While ecological studies show higher burdens of COVID-19 mortality in areas with higher rates of poverty, little is known about social determinants of COVID-19 mortality at the individual level. METHODS AND FINDINGS: We estimated the proportions of COVID-19 deaths by age, sex, race/ethnicity, and comorbid conditions using their reported univariate proportions among COVID-19 deaths and correlations among these variables in the general population from the 2017-2018 National Health and Nutrition Examination Survey (NHANES). We used these proportions to randomly sample individuals from NHANES. We analyzed the distributions of COVID-19 deaths by race/ethnicity, income, education level, and veteran status. We analyzed the association of these characteristics with mortality by logistic regression. Summary demographics of deaths include mean age 71.6 years, 45.9% female, and 45.1% non-Hispanic white. We found that disproportionate deaths occurred among individuals with nonwhite race/ethnicity (54.8% of deaths, 95% CI 49.0%-59.6%, p < 0.001), individuals with income below the median (67.5%, 95% CI 63.4%-71.5%, p < 0.001), individuals with less than a high school level of education (25.6%, 95% CI 23.4% -27.9%, p < 0.001), and veterans (19.5%, 95% CI 15.8%-23.4%, p < 0.001). Except for veteran status, these characteristics are significantly associated with COVID-19 mortality in multiple logistic regression. Limitations include the lack of institutionalized people in the sample (e.g., nursing home residents and incarcerated persons), the need to use comorbidity data collected from outside the US, and the assumption of the same correlations among variables for the noninstitutionalized population and COVID-19 decedents. CONCLUSIONS: Substantial inequalities in COVID-19 mortality are likely, with disproportionate burdens falling on those who are of racial/ethnic minorities, are poor, have less education, and are veterans. Healthcare systems must ensure adequate access to these groups. Public health measures should specifically reach these groups, and data on social determinants should be systematically collected from people with COVID-19.

Correction: Social determinants of mortality from COVID-19: A simulation study using NHANES.

[This corrects the article DOI: 10.1371/journal.pmed.1003490.].

The Societal Value of Vaccination in the Age of COVID-19.

In recent years, academics and policymakers have increasingly recognized that the full societal value of vaccination encompasses broad health, economic, and social benefits beyond avoided morbidity and mortality due to infection by the targeted pathogen and limited health care costs. Nevertheless, standard economic evaluations of vaccines continue to focus on a relatively narrow set of health-centric benefits, with consequences for vaccination policies and public investments.The COVID-19 pandemic illustrates in stark terms the multiplicity and magnitude of harms that infectious diseases may inflict on society. COVID-19 has overtaxed health systems, disrupted routine immunization programs, forced school and workplace closures, impeded the operation of international supply chains, suppressed aggregate demand, and exacerbated existing social inequities.The obvious nature of the pandemic's broad effects could conceivably convince more policymakers to identify and account for the full societal impacts of infectious disease when evaluating the potential benefits of vaccination. Such a shift could make a big difference in how we allocate societal resources in the service of population health and in how much we stand to gain from that spending.

Economic Evaluation of Vaccines: Belgian Reflections on the Need for a Broader Perspective.

OBJECTIVES: The standard framework of economic evaluation of health programs, which is increasingly used for policy funding decisions, is insufficiently equipped to reflect the full range of health and economic benefits conferred by vaccines and thus undervalues vaccination. METHODS: In 2019, a group of Belgian health economic and clinical experts, supported by 2 senior international vaccination experts (1 American, 1 Belgian), convened 4 roundtable meetings to highlight which particular value elements of vaccination remain neglected in economic evaluations. RESULTS: They concluded that the standard economic evaluation framework fails to reflect the full value of vaccination with respect to prevention of complications linked to some vaccine-preventable diseases, health gains for caregivers, herd effects, changes in exposure to and distribution of serotypes, the effect on antimicrobial resistance, productivity gains for caregivers and patients, and the distributive implications of vaccination programs. CONCLUSIONS: Here, suggestions are made regarding how these shortcomings can be addressed in future economic evaluations of vaccines and how a more level playing field between vaccines and other health programs can be created.

Community perceptions of vaccination among influential stakeholders: qualitative research in rural India.

BACKGROUND: In India and other low- and middle-income countries, multiple family and community members are influential in caregivers' perceptions of vaccination. Existing literature indicates the primary caregiver, typically the mother, is instrumental in vaccine decision-making, but this may vary in contexts. We investigated the role of stakeholders in India who influence caregivers' vaccination perceptions, as this is essential to developing strategies to promote vaccine acceptance and improve uptake. METHODS: This research was conducted in 2019 in Mewat District in Haryana, an area in India with extremely low vaccination coverage. We conducted six focus group discussions with 60 participants in the following categories: fathers of children under-5 years old, expectant mothers, mothers-in-law, community health workers, and community influencers such as locally elected officials and religious leaders. RESULTS: Our results highlighted four themes that influence vaccine uptake. First, while caregivers associated vaccination with reductions in specific diseases, they also noted that vaccination services brought broad health gains, including improved nutrition, antenatal guidance, and social support. Second, community health workers critically influenced, positively or negatively, caregivers' vaccination perceptions. Third, community health workers faced gaps in their education such as limited training on vaccine side-effects, placing them at a disadvantage when dealing with families. Finally, we found that mothers-in-law, fathers, and religious leaders influence caregivers' perceptions of vaccination. CONCLUSIONS: Communication of broader benefits of vaccines and vaccination services by community health workers could be impactful in increasing vaccine acceptance. Vaccine uptake could potentially be improved by facilitating community health workers' ownership over vaccine acceptance and uptake by involving them in the design and implementation of interventions to target mothers and mothers-in-law. A 'bottom-up' approach, leveraging community health workers' knowledge to design interventions, and giving a voice to key members of the household and society beyond mothers alone, may sustain health improvement in low vaccine coverage areas.

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.

Emerging infectious diseases: A proactive approach.

Infectious diseases are now emerging or reemerging almost every year. This trend will continue because a number of factors, including the increased global population, aging, travel, urbanization, and climate change, favor the emergence, evolution, and spread of new pathogens. The approach used so far for emerging infectious diseases (EIDs) does not work from the technical point of view, and it is not sustainable. However, the advent of platform technologies offers vaccine manufacturers an opportunity to develop new vaccines faster and to reduce the investment to build manufacturing facilities, in addition to allowing for the possible streamlining of regulatory processes. The new technologies also make possible the rapid development of human monoclonal antibodies that could become a potent immediate response to an emergency. So far, several proposals to approach EIDs have been made independently by scientists, the private sector, national governments, and international organizations such as the World Health Organization (WHO). While each of them has merit, there is a need for a global governance that is capable of taking a strong leadership role and making it attractive to all partners to come to the same table and to coordinate the global approach.

Impact of Pneumococcal Vaccination on Pneumonia Hospitalizations and Related Costs in Ontario: A Population-Based Ecological Study.

Background: In Ontario, Canada, pneumococcal conjugate vaccine (PCV) was approved for infants in 2001 and became part of the publicly funded routine immunization schedule in 2005. We assessed the population-level impact of PCV on pneumonia hospitalizations and related costs. Methods: We used the difference-in-differences approach to evaluate the impact of pneumococcal vaccination on pneumonia hospitalizations and related costs, using nonpneumonia hospitalization as the control condition. We extracted monthly hospitalization costs, stratified by age group, from population-based health administrative data between April 1992 and March 2014. The study period was divided into 5 intervals: prevaccine period, availability of 7-valent PCV (PCV7) for private purchase, public funding for PCV7, replacement of PCV7 with 10-valent PCV (PCV10), and replacement of PCV10 with 13-valent PCV (PCV13). Results: A total of 1063700 pneumonia hospitalizations were recorded during the study period. In the vaccine-eligible age group, pneumonia hospitalizations declined by 34% (95% confidence interval, 32%-37%), 38% (32%-43%), and 45% (40%-51%) and hospitalization-related costs declined by 38% (25%-51%), 39% (33%-45%), and 46% (41%-52%) after public funding for PCV7, PCV10, and PCV13, respectively. Pneumonia hospitalizations and related costs also declined substantially for PCV-ineligible older children and elderly persons (aged >65 years). Conclusions: Our results suggest that the publicly funded PCV immunization program is responsible for substantial reductions in pneumonia hospitalizations and related healthcare costs, among both young children eligible for publicly funded vaccination and other age groups not included in the publicly funded program.

Priority setting in health: development and application of a multi-criteria algorithm for the population of New Zealand's Waikato region.

BACKGROUND: Priority setting in a climate of diverse needs and limited resources is one of the most significant challenges faced by health care policymakers. This paper develops and applies a comprehensive multi-criteria algorithm to help determine the relative importance of health conditions that affect a defined population. METHODS: Our algorithm is implemented in the context of the Waikato District Health Board (WDHB) in New Zealand, which serves approximately 10% of the New Zealand population. Strategic priorities of the WDHB are operationalized into five criteria along which the algorithm is structured-scale of disease, household financial impact of disease, health equity, cost-effectiveness, and multimorbidity burden. Using national-level data and published literature from New Zealand, the World Health Organization, and other high-income Commonwealth countries, 25 health conditions in Waikato are identified and mapped to these five criteria. These disease-criteria mappings are weighted with data from an ordered choice survey administered to the general public of the Waikato region. The resulting output of health conditions ranked in order of relative importance is validated against an explicit list of health concerns, provided by the survey respondents. RESULTS: Heart disease and cancerous disorders are assigned highest priority rankings according to both the algorithm and the survey data, suggesting that our model is aligned with the primary health concerns of the general public. All five criteria are weighted near-equal across survey respondents, though the average health equity preference score is 9.2% higher for Maori compared to non-Maori respondents. Older respondents (50 years and above) ranked issues of multimorbidity 4.2% higher than younger respondents. CONCLUSIONS: Health preferences of the general population can be elicited using ordered-choice surveys and can be used to weight data for health conditions across multiple criteria, providing policymakers with a practical tool to inform which health conditions deserve the most attention. Our model connects public health strategic priorities, the health impacts and financial costs of particular health conditions, and the underlying preferences of the general public. We illustrate a practical approach to quantifying the foundational criteria that drive public preferences, for the purpose of relevant, legitimate, and evidence-based priority setting in health.

The economic burden of noncommunicable diseases and mental health conditions: results for Costa Rica, Jamaica, and Peru.

OBJECTIVE: We extend the EPIC model of the World Health Organization (WHO) and apply it to analyze the macroeconomic impact of noncommunicable diseases (NCDs) and mental health conditions in Costa Rica, Jamaica, and Peru. METHODS: The EPIC model quantifies the impact of NCDs and mental health conditions on aggregate output solely through the effect of chronic conditions on labor supply due to mortality. In contrast, the expanded EPIC-H Plus framework also incorporates reductions in effective labor supply due to morbidity and negative effects of health expenditure on output via the diversion of productive savings and reduced capital accumulation. We apply this methodology to Costa Rica, Jamaica, and Peru and estimate gross domestic product (GDP) output lost due to four leading NCDs (cardiovascular disease, cancer, chronic respiratory disease, and diabetes) and mental health conditions in these countries from 2015 to 2030. We also estimate losses from all NCDs and mental health conditions combined. RESULTS: Overall, our results show total losses associated with all NCDs and mental health conditions over the period 2015-2030 of US$ 81.96 billion (2015 US$) for Costa Rica, US$ 18.45 billion for Jamaica, and US$ 477.33 billion for Peru. Moderate variation exists in the magnitude of the burdens of diseases for the three countries. In Costa Rica and Peru, respiratory disease and mental health conditions are two leading contributors to lost output, while in Jamaica, cardiovascular disease alone accounts for 20.8% of the total loss, followed by cancer. CONCLUSIONS: These results indicate that the economic impact of NCDs and mental health conditions is substantial and that interventions to reduce the prevalence of chronic conditions in countries of Latin America and the Caribbean are likely to be highly cost-beneficial.

Market mechanisms for newborn health in Nepal.

BACKGROUND: In Nepal, hypothermia is a major risk factor for newborn survival, but the country's public health care sector has insufficient capacity to improve newborn survival given the burden imposed by distance to health facilities and cost. Low-cost technology to provide newborn thermal care in resource-limited environments exists, but lacks effective distribution channels. This study aims to develop a private sector distribution model for dedicated newborn thermal care technology to ensure equitable access to thermal protection and ultimately improve newborn health in Nepal. METHODS: We conducted a document analysis of newborn health policy in Nepal and a scoping literature review of approaches to newborn hypothermia in the region, followed by qualitative interviews with key stakeholders of newborn health in Nepal. RESULTS: Current solutions addressing newborn hypothermia range from high-technology, high-cost incubators to low-cost behavioral interventions such as skin-to-skin care. However, none of these interventions  are currently implemented at scale. A distribution model that provides incentives for community health volunteers and existing public health services in Nepal can deliver existing low-cost infant warmers to disadvantaged mothers where and when needed. Newborn technology can serve as an adjunct to skin-to-skin care and potentially create demand for newborn care practices. CONCLUSION: Harnessing market forces could promote public health by raising awareness of newborn challenges, such as newborn hypothermia, and triggering demand for appropriate health technology and related health promotion behaviors. Market approaches to promoting public health have been somewhat neglected, especially in economically disadvantaged and vulnerable populations, and deserve greater attention in Nepal and other settings with limited public health service delivery capacity.