Priority setting in early childhood development: an analytical framework for economic evaluation of interventions

BACKGROUND: Early childhood development (ECD) sets the foundation for healthy and successful lives with important ramifications for education, labour market outcomes and other domains of well-being. Even though a large number of interventions that promote ECD have been implemented and evaluated globally, there is currently no standardised framework that allows a comparison of the relative cost-effectiveness of these interventions. METHODS: We first reviewed the existing literature to document the main approaches that have been used to assess the relative effectiveness of interventions that promote ECD, including early parenting and at-home psychosocial stimulation interventions. We then present an economic evaluation framework that builds on these reviewed approaches and focuses on the immediate impact of interventions on motor, cognitive, language and socioemotional skills. Last, we apply our framework to compute the relative cost-effectiveness of interventions for which recent effectiveness and costing data were published. For this last part, we relied on a recently published review to obtain effect sizes documented in a consistent manner across interventions. FINDINGS: Our framework enables direct value-for-money comparison of interventions across settings. Cost-effectiveness estimates, expressed in $ per units of improvement in ECD outcomes, vary greatly across interventions. Given that estimated costs vary by orders of magnitude across interventions while impacts are relatively similar, cost-effectiveness rankings are dominated by implementation costs and the interventions with higher value for money are generally those with a lower implementation cost (eg, psychosocial interventions involving limited staff). CONCLUSIONS: With increasing attention and investment into ECD programmes, consistent assessments of the relative cost-effectiveness of available interventions are urgently needed. This paper presents a unified analytical framework to address this need and highlights the rather remarkable range in both costs and cost-effectiveness across currently available intervention strategies

A Toxicogenomics Approach to Identify New Plausible Epigenetic Mechanisms of Ochratoxin A Carcinogenicity in Rat

Ochratoxin A (OTA) is a mycotoxin occurring naturally in a wide range of food commodities. In animals, it has been shown to cause a variety of adverse effects, nephrocarcinogenicity being the most prominent. Because of its high toxic potency and the continuous exposure of the human population, OTA has raised public health concerns. There is significant debate on how to use the rat carcinogenicity data to assess the potential risk to humans. In this context, the question of the mechanism of action of OTA appears of key importance and was studied through the application of a toxicogenomics approach. Male Fischer rats were fed OTA for up to 2 years. Renal tumors were discovered during the last 6 months of the study. The total tumor incidence reached 25% at the end of the study. Gene expression profile was analyzed in groups of animals taken in intervals from 7 days to 12 months. Tissue-specific responses were observed in kidney versus liver. For selected genes, microarray data were confirmed at both mRNA and protein levels. In kidney, several genes known as markers of kidney injury and cell regeneration were significantly modulated by OTA. The expression of genes known to be involved in DNA synthesis and repair, or genes induced as a result of DNA damage, was only marginally modulated. Very little or no effect was found amongst genes associated with apoptosis. Alterations of gene expression indicating effects on calcium homeostasis and a disruption of pathways regulated by the transcription factors hepatocyte nuclear factor 4 alpha (HNF4α) and nuclear factor-erythroid 2-related factor 2 (Nrf2) were observed in the kidney but not in the liver. Previous data have suggested that a reduction in HNF4α may be associated with nephrocarcinogenicity. Many Nrf2-regulated genes are involved in chemical detoxication and antioxidant defense. The depletion of these genes is likely to impair the defense potential of the cells, resulting in chronic elevation of oxidative stress in the kidney. The inhibition of defense mechanism appears as a highly plausible new mechanism, which could contribute to OTA carcinogenicit

Estimating the distribution of morbidity and mortality of childhood diarrhea, measles, and pneumonia by wealth group in low- and middle-income countries

__Background:__ Equitable access to vaccines has been suggested as a priority for low- and middle-income countries (LMICs). However, it is unclear whether providing equitable access is enough to ensure health equity. Furthermore, disaggregated data on health outcomes and benefits gained across population subgroups are often unavailable. This paper develops a model to estimate the distribution of childhood disease cases and deaths across socioeconomic groups, and the potential benefits of three vaccine programs in LMICs. __Methods:__ For each country and for three diseases (diarrhea, measles, pneumonia), we estimated the distributions of cases and deaths that would occur across wealth quintiles in the absence of any immunization or treatment programs, using both the prevalence and relative risk of a set of risk and prognostic factors. Building on these baseline estimates, we examined what might be the impact of three vaccines (first dose of measles, pneumococcal conjugate, and rotavirus vaccines), under five scenarios based on different sets of quintile-specific immunization coverage and disease treatment utilization rates. __Results:__ Due to higher prevalence of risk factors among the poor, disproportionately more disease cases and deaths would occur among the two lowest wealth quintiles for all three diseases when vaccines or treatment are unavailable. Country-specific context, including how the baseline risks, immunization coverage, and treatment utilization are currently distributed across quintiles, affects how different policies translate into changes in cases and deaths distribution. __Conclusions:__ Our study highlights several factors that would substantially contribute to the unequal distribution of childhood diseases, and finds that merely ensuring equal access to vaccines will not reduce the health outcomes gap across wealth quintiles. Such information can inform policies and planning of programs that aim to improve equitable delivery of healthcare services

Estimation of distribution of childhood diarrhoea, measles, and pneumonia morbidity and mortality by socio-economic group in low-income and middle-income countries

Background Vaccines are one of the most successful interventions in improving population health in low-income and middle-income countries (LMICs). In addition to the direct improvements in health outcomes, we are interested in their distributional effects—that is, whether vaccines promote or reduce health equity across socioeconomic groups. Empirical data on incidence and mortality of vaccine-preventable diseases across socioeconomic groups is not available. Therefore, we developed a method to estimate the distribution of childhood diseases and deaths across income groups and the benefits of three vaccines—for diarrhoea, measles, and pneumonia—in 41 LMICs. Methods For every country and disease (diarrhoea, measles, pneumonia), we estimated the distribution of cases and deaths that would occur in each income quintile had there been no immunisation or treatment programme, using both the prevalence and relative risk of a set of risk and prognostic factors. Building on these baseline estimates, we assessed the effect of three vaccines (first dose of measles vaccine, pneumococcal conjugate vaccine, and rotavirus vaccine) under five scenarios based on sets of quintile-specific immunisation coverage and uptake of disease treatment. Findings Because the prevalence of risk factors is higher in the poorest two quintiles than in the rest of the population, more disease cases and deaths would occur in the poorest two quintiles for all three diseases when vaccines or treatment are unavailable. However, we noted that current immunisation coverage and treatment utilisation rates have resulted in greater inequity in the distribution of cases and deaths. Even if in absolute terms the poorest quintiles benefit more from vaccines, the wealthier two quintiles sees a higher percentage decrease in cases and deaths. Thus, in terms of overall distribution of remaining cases and deaths with vaccine coverage, the poorest quintiles would see a higher comparative burden of disease than they would without vaccine coverage. Country-specific context, including how the baseline risks, immunisation coverage, and treatment utilisation are currently distributed across quintiles, affects how different policies translate to improvements in the distribution of cases and deaths. Interpretation Our analysis highlights several factors, including risk and prognostic factors, and vaccine and treatment coverage that would substantially contribute to the unequal distribution of childhood diseases, and we found that merely ensuring equal access to vaccines will not reduce the health outcomes gap between income quintiles. Such information can inform policies and planning of programmes that aim to improve equitable delivery of healthcare services

Timing and cost of scaling up surgical services in low-income and middle-income countries from 2012 to 2030 : a modelling study

Background: Given the large burden of surgical conditions and the crosscutting nature of surgery, scale-up of basic surgical services is crucial to health-system strengthening. The Lancet Commission on Global Surgery proposed that, to meet populations' needs, countries should achieve 5000 major operations per 100 000 population per year. We modelled the possible scale-up of surgical services in 88 low-income and middle-income countries with a population greater than 1 million from 2012 to 2030 at various rates and quantified the associated costs. Methods: Major surgery includes any intervention within an operating room involving tissue manipulation and anaesthesia. We used estimates for the number of major operations achieved per country annually and the number of operating rooms per region, and data from Mongolia and Mexico for trends in the number of operations. Unit costs included a cost per operation, proxied by caesarean section cost estimates; hospital construction data were used to estimate cost per operating room construction. We determined the year by which each country would achieve the Commission's target. We modelled three scenarios for the scale-up rate: actual rates (5·1% per year) and two "aspirational" rates, the rates achieved by Mongolia (8·9% annual) and Mexico (22·5% annual). We subsequently estimated the associated costs. Findings: About half of the 88 countries would achieve the target by 2030 at actual rates of improvements, with up to two-thirds if the rate were increased to Mongolian rates. We estimate the total costs of achieving scale-up at US$300-420 billion (95% UI 190-600 billion) over 2012-30, which represents 4-8% of total annual health expenditures among low-income and lower middle-income countries and 1% among upper middle-income countries. Interpretation: Scale-up of surgical services will not reach the target of 5000 operations per 100 000 by 2030 in about half of low-income and middle-income countries without increased funding, which countries and the international community must seek to achieve expansion of quality surgical services

Comparing the impact on COVID-19 mortality of self-imposed behavior change and of government regulations across 13 countries.

OBJECTIVE: Countries have adopted different approaches, at different times, to reduce the transmission of coronavirus disease 2019 (COVID-19). Cross-country comparison could indicate the relative efficacy of these approaches. We assess various nonpharmaceutical interventions (NPIs), comparing the effects of voluntary behavior change and of changes enforced via official regulations, by examining their impacts on subsequent death rates. DATA SOURCES: Secondary data on COVID-19 deaths from 13 European countries, over March-May 2020. STUDY DESIGN: We examine two types of NPI: the introduction of government-enforced closure policies and self-imposed alteration of individual behaviors in the period prior to regulations. Our proxy for the latter is Google mobility data, which captures voluntary behavior change when disease salience is sufficiently high. The primary outcome variable is the rate of change in COVID-19 fatalities per day, 16-20 days after interventions take place. Linear multivariate regression analysis is used to evaluate impacts. DATA COLLECTION/EXTRACTION METHODS: publicly available. PRINCIPAL FINDINGS: Voluntarily reduced mobility, occurring prior to government policies, decreases the percent change in deaths per day by 9.2 percentage points (pp) (95% confidence interval [CI] 4.5-14.0 pp). Government closure policies decrease the percent change in deaths per day by 14.0 pp (95% CI 10.8-17.2 pp). Disaggregating government policies, the most beneficial for reducing fatality, are intercity travel restrictions, canceling public events, requiring face masks in some situations, and closing nonessential workplaces. Other sub-components, such as closing schools and imposing stay-at-home rules, show smaller and statistically insignificant impacts. CONCLUSIONS: NPIs have substantially reduced fatalities arising from COVID-19. Importantly, the effect of voluntary behavior change is of the same order of magnitude as government-mandated regulations. These findings, including the substantial variation across dimensions of closure, have implications for the optimal targeted mix of government policies as the pandemic waxes and wanes, especially given the economic and human welfare consequences of strict regulations

Accounting for Equity Considerations in Cost-Effectiveness Analysis : A Systematic Review of Rotavirus Vaccine in Low- and Middle-Income Countries

Additional file 3: Appendix C. Full data table of results

The impact of the introduction of new recognition criteria for overwork-related cardiovascular and cerebrovascular diseases: a cross-country comparison

Cardiovascular and cerebrovascular diseases (CVDs) related to overwork are common in Asia, as is death from overwork, known as karoshi. Japan was the first country in the world to introduce criteria for recognizing overwork-related CVDs in 1961. Taiwan followed Japan in putting in place new policies and then updating these in 2010. We aimed to investigate the effect of introducing the new criteria for recognizing overwork-related CVDs in both countries. We defined the baseline period as the 5 years before launch of the new criteria, then collected data to 5 years after the new criteria. We applied a Poisson regression model to analyze the longitudinal change in rates of overwork-related CVDs before and after, adjusting for indicators of working conditions. Implementation of the new criteria was associated with a 2.58-fold increase in the rate of overwork-related CVDs (p-value < 0.05). However, the examined policy framework in Taiwan still appears to miss a substantial number of cases compared to that are captured by a similar policy framework used to capture overwork-related CVD rates in Japan by a factor of 0.42 (p-value < 0.05). Accordingly, we make a case for enhancements of Taiwan’s system for reporting and recognizing overwork-related diseases and deaths

How can we evaluate the cost-effectiveness of health system strengthening? A typology and illustrations

Health interventions often depend on a complex system of human and capital infrastructure that is shared with other interventions, in the form of service delivery platforms, such as healthcare facilities, hospitals, or community services. Most forms of health system strengthening seek to improve the efficiency or effectiveness of such delivery platforms. This paper presents a typology of ways in which health system strengthening can improve the economic efficiency of health services. Three types of health system strengthening are identified and modelled: (1) investment in the efficiency of an existing shared platform that generates positive benefits across a range of existing interventions; (2) relaxing a capacity constraint of an existing shared platform that inhibits the optimization of existing interventions; (3) providing an entirely new shared platform that supports a number of existing or new interventions. Theoretical models are illustrated with examples, and illustrate the importance of considering the portfolio of interventions using a platform, and not just piecemeal individual analysis of those interventions. They show how it is possible to extend principles of conventional cost-effectiveness analysis to identify an optimal balance between investing in health system strengthening and expenditure on specific interventions. The models developed in this paper provide a conceptual framework for evaluating the cost-effectiveness of investments in strengthening healthcare systems and, more broadly, shed light on the role that platforms play in promoting the cost-effectiveness of different interventions

The equity impact vaccines may have on averting deaths and medical impoverishment in developing countries

With social policies increasingly directed toward enhancing equity through health programs, it is important that methods for estimating the health and economic benefits of these programs by subpopulation be developed, to assess both equity concerns and the programs’ total impact. We estimated the differential health impact (measured as the number of deaths averted) and household economic impact (measured as the number of cases of medical impoverishment averted) of ten antigens and their corresponding vaccines across income quintiles for forty-one low- and middle-income countries. Our analysis indicated that benefits across these vaccines would accrue predominantly in the lowest income quintiles. Policy makers should be informed about the large health and economic distributional impact that vaccines could have, and they should view vaccination policies as potentially important channels for improving health equity. Our results provide insight into the distribution of vaccine-preventable diseases and the health benefits associated with their prevention