Evaluating Health Expenditure Trends and Disease Burden in India: A Cost per DALY Approach.

Background: Efficient allocation of healthcare resources requires a comprehensive evaluation of healthcare spending and its impact on disease burden. This study aims to estimate the costs-per disability-adjusted life years (DALY) in India. Data from 2010 to 2019 on DALYs and health expenditure per capita (HEp) for individual states in India were utilised. Design and Methods: We followed the CHEERS statement 2022 to present our study's methodology and outcomes. Pearson's product-moment correlations were used to analyse associations between DALYs and HEp. A panel regression analysis was conducted using a log regression model to estimate changes in DALYs due to health expenditure changes. All costs are reported in Indian rupee (₹) along with its 95% CI, with a conversion factor of 1 US$ = ₹82.4 applied. Results: The costs-per-DALY were estimated for each state and India. DALY was negatively correlated with HEp. The estimated mean cost-per-DALY for India was ₹82,112 (₹55,810 to ₹1,08,413) [$997 ($667 to $1316)]. The mean cost per-DALY varied across states, with value of ₹27,058 (₹22,250 to ₹31,866) [$328 ($270 to $387)] for states in the first quartile based on Human Development Index (HDI) and ₹2,69,175 (₹1,05,946 to ₹4,32,404) [$3267 ($1286 to $5248)] for those in fourth HDI quartile. States such as Gujarat (0.16), Karnataka (0.17) and Maharashtra (0.22) have lower, and Arunachal Pradesh has the highest cost-per-DALY to Gross state domestic product per-capita ratio (2.41), followed by Nagaland (1.45). Conclusion: Higher healthcare investment has a lower disease burden; however, reduction in DALY varies across states. Study findings provide evidence to aid the setting up of differential willingness-to-pay thresholds across Indian states for efficient and equitable healthcare resource allocation.

Pharmacogenomics-assisted schizophrenia management: A hybrid type 2 effectiveness-implementation study protocol to compare the clinical utility, cost-effectiveness, and barriers.

OBJECTIVES: The response to antipsychotic therapy is highly variable. Pharmacogenomic (PGx) factors play a major role in deciding the effectiveness and safety of antipsychotic drugs. A hybrid type 2 effectiveness-implementation research will be conducted to evaluate the clinical utility (safety and efficacy), cost-effectiveness, and facilitators and barriers in implementing PGx-assisted management compared to standard of care in patients with schizophrenia attending a tertiary care hospital in eastern India. METHODS: In part 1, a randomized controlled trial will be conducted. Adult patients with schizophrenia will be randomized (2: 1) to receive PGx-assisted treatment (drug and regimen selection depending on the results of single-nucleotide polymorphisms in genes DRD2, HTR1A, HTR2C, ABCB1, CYP2D6, CYP3A5, and CYP1A2) or the standard of care. Serum drug levels will be measured. The patients will be followed up for 12 weeks. The primary endpoint is the difference in the Udvalg for Kliniske Undersøgelser Side-Effect Rating Scale score between the two arms. In part 2, the cost-effectiveness of PGx-assisted treatment will be evaluated. In part 3, the facilitators and barriers to implementing PGx-assisted treatment for schizophrenia will be explored using a qualitative design. EXPECTED OUTCOME: The study findings will help in understanding whether PGx-assisted management has a clinical utility, whether it is cost-effective, and what are the facilitators and barriers to implementing it in the management of schizophrenia. TRIAL REGISTRATION: The study has been registered with the Clinical Trials Registry-India (CTRI/2023/08/056210).

Cost Effectiveness of Deep Brain Stimulation for Parkinson's Disease: A Systematic Review.

BACKGROUND AND OBJECTIVE: Deep brain stimulation (DBS) is an established treatment for Parkinson's disease (PD) in patients with advanced motor symptoms with an inadequate response to pharmacotherapies. Despite its effectiveness, the cost effectiveness of DBS remains a subject of debate. This systematic review aims to update and synthesize evidence on the cost effectiveness of DBS for PD. METHODS: To identify full economic evaluations that compared the cost effectiveness of DBS with other best medical treatments, a comprehensive search was conducted of the PubMed, Embase, Scopus, and Tufts Cost-Effective Analysis registry databases. The selected papers were systematically reviewed, and the results were summarized. For the quality appraisal, we used the modified economic evaluations bias checklist. The review protocol was a priori registered with PROSPERO, CRD42022345508. RESULTS: Sixteen identified cost-utility analyses that reported 19 comparisons on the use of DBS for PD were systematically reviewed. The studies were primarily conducted in high-income countries and employed Markov models. The costs considered were direct costs: surgical expenses, calibration, pulse generator replacement, and annual drug expenses. The majority of studies used country-specific thresholds. Fourteen comparisons from 12 studies reported on the cost effectiveness of DBS compared to best medical treatments. Eleven comparisons reported DBS as cost effective based on incremental cost-utility ratio results. CONCLUSIONS: The cost effectiveness of DBS for PD varies by time horizon, costs considered, threshold utilized, and stage of PD progression. Standardizing approaches and comparing DBS with other treatments are needed for future research on effective PD management.

Household catastrophic health expenditures for rheumatoid arthritis: a single centre study from South India.

Rheumatoid arthritis (RA) not only has a physical and emotional toll but also has a substantial economic impact. This study aims to estimate the burden of catastrophic health expenditure (CHE) on households due to RA in Tamil Nadu, India. We conducted cross-sectional descriptive hospital-based single-centre study at a tertiary care private multispecialty hospital in Tamil Nadu, India. The study comprised 320 RA patients who visited the outpatient clinic from April to October 2022. Demographic and baseline descriptive characteristics were reported. Multivariable logistic regression analyses were performed to identify major determinants associated with CHE. We also examined the inequality in household annual income and CHE. Most study participants were females (88.1%) with a mean age (SD) of 55.57 ± 12.29 years. About 93% of RA patients were from urban areas, and 89.4% were literate. Only 8.1% of respondents reported having health insurance. Households experiencing CHE owing to RA were 51.4% (n = 162). The mean (95% CI) annual health expenditure for treating RA is ₹44,700 (₹41,710 to 47,690) with a median (IQR) of ₹39,210 (₹25,500) [$476 ($310)]. The corresponding mean (95% CI) and median (IQR) Out of pocket expenditure among RA patients per household were ₹40,698 (₹38,249 to 43,148) [$494 ($464 to $524)] and ₹36,450 (23,070) [$442 ($280)] respectively. Nearly half of the households with RA patients had a financial catastrophe due to healthcare costs being paid out-of-pocket and limited health insurance coverage. The results underscore the need for comprehensive approaches to strengthening public health policies along with financial risk protection and quality care in India.

Cost-effectiveness of tumor necrosis factor-alpha inhibitors: a systematic review and meta-analysis of cost-utility studies.

OBJECTIVE: To systematically review the cost-utility evidence of TNF-a-i treatment for rheumatoid arthritis (RA) and to estimate the pooled incremental net benefit (INBp). METHODS: We selected economic evaluation studies reporting the cost-utility of TNF-a-i compared to other disease-modifying anti-rheumatic drugs (DMARDs) after a systematic search in PubMed, Embase, Scopus, and Tufts Medical Centers' cost-effective analysis registry. The results were reported as pooled INB in purchasing power parity-adjusted US dollars, along with 95% confidence intervals. We used GRADE quality assessment to present summaries of evidence and random-effects meta-analysis to synthesize cost-utility of TNF-a-i. RESULTS: We included 86 studies for systematic review, of which 27 for meta-analysis. TNF-a-i is not cost-effective [$ -4,129(-6,789 to -1,469)] compared to other DMARDs but with high heterogeneity. There was no evidence of publication bias (p = 0.447). On separate analysis, TNF-a-i is not cost-effective [$ -4,805(-7,882 to -1,728)] compared to conventional synthetic DMARDs for RA treatment. GRADE assessment indicated very low confidence in pooled cost-utility results and likely presence of risk of bias on the overall ECOBIAS checklist in studies. CONCLUSION: Based on the available evidence during the study period, TNF-a-i is not a cost-effective option for treating RA compared to other DMARDs. However, high heterogeneity and low confidence in GRADE quality assessment preclude the results from being generalizable.

Cost-utility of Ranolazine for Chronic Stable Angina Pectoris: Systematic Review and Meta-analysis.

PURPOSE: Ranolazine is used to treat stable angina pectoris, the most common symptom of ischemic heart disease. Appropriate management of chronic stable angina pectoris is essential from both a clinical and an economic view point. METHODS: This systematic review and meta-analysis adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included cost-utility analyses, which compared ranolazine with other standard treatments for treating stable angina pectoris. The search was conducted in PubMed, EMBASE, and Scopus databases. A random-effects model based on the DerSimonian and Laird method was used to pool the incremental net benefit reported in purchasing power parity adjusted US dollars. The modified economic evaluation checklist was used to assess the risk of bias. FINDINGS: The pooled results from 7 selected studies with a time horizon of 1 year show that add-on ranolazine was significantly cost-effective compared with standard treatment, with a pooled incremental net benefit of US$1335 (95% CI, 500 to 2169) but with substantial heterogeneity (I2 = 79.46%). On subgroup analysis, ranolazine was cost-effective from the payers' perspective (US$1975; 95% CI, 1042 to 2908; I2 = 69.23) but not from a societal perspective (US$297; 95% CI, -241 to 715; I2 = 0%)]. There was limited evidence from lower economies. IMPLICATIONS: Pooled evidence suggests that add-on ranolazine therapy is cost-effective for chronic stable angina pectoris up to a 1-year time horizon. There is a lacuna of evidence from low- and middle-income countries and on long-term cost-effectiveness. The current evidence synthesis may provide a macroeconomic point of view for policy makers regarding the direction of ranolazine's cost-effectiveness for evidence-informed policy-making. PROSPERO identifier: CRD42022332454.

Cost Effectiveness of Rituximab Therapy for Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of Cost-Utility Studies.

BACKGROUND AND OBJECTIVES: Depletion of B cells is shown to be clinically effective for rheumatoid arthritis (RA) treatment. Although B-cell depletion therapy with rituximab is indicated for RA patients who have failed to other disease-modifying anti-rheumatic drugs (DMARDs), primary cost-effectiveness evidence is inconsistent. We aimed to provide synthesised cost-effectiveness evidence of rituximab in the treatment of RA compared to other DMARDs, since the published cost-effectiveness evidence is mixed. METHODS: We identified economic evaluation studies reporting cost-utility of rituximab compared to other DMARDs by searching PubMed, Embase, Scopus, and Tufts Cost-Effective Analysis registry. Using random-effects meta-analysis, we pooled incremental net benefit (INB) in (purchasing power parity) adjusted US$ with 95% confidence intervals. We used the modified economic evaluations bias checklist and Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) instrument for quality appraisal. The study protocol was pre-registered with PROSPERO, CRD 42021222541. RESULTS: Of the selected 18 studies, the majority were from high-income countries (n = 14) followed by upper middle-income countries (n = 3) and lower middle-income countries (n = 1), with minimal risk of bias. Rituximab is significantly cost effective with a pooled INB (95% CI) of $8767 (720 to 16,814). On subgroup analysis, rituximab is significantly cost effective from a health system perspective [$12,832 (3392 to 22,272)], for studies using 3.5% discount rate [$15,468 (5973 to 24,963)] and a for a time horizon of less than 5 years [$8496 (1547 to 15,445)]. In a separate analysis, rituximab as third-line therapy (for conventional synthetic DMARDs followed by any other biologic DMARD failed patients) was not cost effective compared to DMARDs [$5314 (-2278 to 12,905)]. Further, the GRADE assessment indicated very-low confidence in the pooled results. CONCLUSION: Rituximab is cost effective compared to other DMARDs but not if used as third-line therapy after failure of biologics. There is a need to generate context-specific evidence for the lower income settings.

Household catastrophic health expenditure for COVID-19 during March-August 2021, in South India: a cross-sectional study.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic increased the utilisation of healthcare services. Such utilization could lead to higher out-of-pocket expenditure (OOPE) and catastrophic health expenditures (CHE). We estimated OOPE and the proportion of households that experienced CHE by conducting a cross-sectional survey of 1200 randomly selected confirmed COVID-19 cases. METHODS: A cross-sectional survey was conducted by telephonic interviews of 1200 randomly selected COVID-19 patients who tested positive between 1 March and 31 August 2021. We collected household-level information on demographics, income, expenditure, insurance coverage, direct medical and non-medical costs incurred toward COVID-19 management. We estimated the proportion of CHE with a 95% confidence interval. We examined the association of household characteristics; COVID-19 cases, severity, and hospitalisation status with CHE. A multivariable logistic regression analysis was conducted to ascertain the effects of variables of interest on the likelihood that households face CHE due to COVID-19. RESULTS: The mean (95%CI) OOPE per household was INR 122,221 (92,744-1,51,698) [US$1,643 (1,247-2,040)]. Among households, 61.7% faced OOPE, and 25.8% experienced CHE due to COVID-19. The odds of facing CHE were high among the households; with a family member over 65 years [OR = 2.89 (2.03-4.12)], with a comorbid individual [OR = 3.38 (2.41-4.75)], in the lowest income quintile [OR = 1.82 (1.12-2.95)], any member visited private hospital [OR = 11.85 (7.68-18.27)]. The odds of having CHE in a household who have received insurance claims [OR = 5.8 (2.81- 11.97)] were high. Households with one and more than one severe COVID-19 increased the risk of CHE by more than two-times and three-times respectively [AOR = 2.67 (1.27-5.58); AOR = 3.18 (1.49-6.81)]. CONCLUSION: COVID-19 severity increases household OOPE and CHE. Strengthening the public healthcare and health insurance with higher health financing is indispensable for financial risk protection of households with severe COVID-19 from CHE.

Cost-effectiveness of cholecystectomy compared to conservative management in people presenting with uncomplicated symptomatic gallstones or cholecystitis in India.

OBJECTIVES: Gallstone diseases impose a significant economic burden on the health care system; thus, determining cost-effective management for gallstones is essential. We aim to estimate the cost-effectiveness of cholecystectomy compared with conservative management in individuals with uncomplicated symptomatic gallstones or cholecystitis in India. METHODS: A decision-analytic Markov model was used to compare the costs and QALY of early laparoscopic cholecystectomy (ELC), delayed laparoscopic cholecystectomy (DLC), and conservative management (CM) in patients with symptomatic uncomplicated gallstone/cholecystitis from an Indian health system perspective. Incremental cost-effectiveness ratio (ICER) was calculated. One-way and probabilistic sensitivity analyses were performed to test parameter uncertainties. RESULTS: ELC and DLC, compared to CM, incurred an incremental cost of -₹10,948 ($146) and ₹1,054 ($14) for the 0.032 QALYs gained. The ICER was -₹3,42,758 ($4577) for ELC vs. CM, and ₹33,183 ($443) for DLC vs. CM, suggesting ELC and DLC are cost-effective. ELC saved ₹12,001 ($160) for 0.0002 QALYs gained compared to DLC, resulting in an ICER of -₹6,43,89,441 ($8,59,733). The results were robust to changes in the input parameters in sensitivity analyses. CONCLUSION: ELC is dominant compared to both DLC and CM, and DLC is more cost-effective than CM. Thus, ELC may be preferable to other gallstone disease managements.

Air Pollution and Cardiovascular Disease Burden: Changing Patterns and Implications for Public Health in India.

INTRODUCTION: The link between air pollution-attributed cardiovascular disease (APACVD) burden and its contributing factors can aid in detecting vulnerabilities and providing forewarnings for India. METHODS: We examined the association between the status and trends of the APACVD burden obtained from the Global Burden of Diseases and Injuries study with the two development metrics in India; the human development index (HDI) and indirect indices of economic development, namely annual new motor vehicle registration and the number of functional factories for 10 years from 2009 to 2019. Lorenz curves and concentration index were used to estimate the inequalities in the state-APACVD burden and the burden per 100,000 population. RESULTS: At the state level, APACVD burden was inversely related to the HDI value in India for the years 2009 (r=-0.48), 2014 (r=-0.47), and 2019 (r=-0.37), and the association was statistically significant (p<0.05). The correlation between state-level APACVD burden with the annual new motor vehicle registration and the number of functional factories in India for these years was also positive and significant (p<0.05). The APACVD was 53% unequally distributed across the states, with a concentration index of 0.53 in 2009. DISCUSSION: We observed that at the state level, the APACVD burden was inversely related to HDI. But the APACVD burden increased with the country's economic development. Also, the excess APACVD burden appears to be attributable to the economically developed states. CONCLUSION: At the state level, APACVD burden decreased as HDI rose over time, indicating that the burden increased with the country's economic development. It is noticeable that the economically developed states may be contributing a higher share of the APACVD burden in India.

Cost-effectiveness of janus kinase inhibitors for rheumatoid arthritis: A systematic review and meta-analysis of cost-utility studies.

Introduction: Janus kinase inhibitors (JAK-i), a class of targeted synthetic disease-modifying antirheumatic drugs (tDMARDs), are suggested as second or third-line therapies in rheumatoid arthritis (RA). Synthesized cost-effective evidence would aid in informed decision-making given the similar clinical effectiveness of JAKi, but incongruent cost-effectiveness reports. Methods: Literature search was conducted in PubMed, Embase, Scopus, and Tufts Medical Centers' cost-effective analysis registry. We pooled the incremental net benefit (INB) with 95% confidence interval (CI) using random-effects model and the heterogeneity was assessed using Cochrane-Q test and I2 statistic. Modified economic evaluation bias checklist was used to assess the quality of selected studies. Publication bias was assessed using a funnel plot and Egger's test. The Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) assessment was performed to assess the certainty of outcomes presented. Results: We included seventeen relevant studies for systematic review, of which fifteen were eligible for meta-analysis. The meta-analysis results showed that JAK-i is cost-effective compared to csDMARDS/bDMARDs with a pooled INB (INBp) of $19,886 (95% CI, 1,635 to 38,137) but with considerable heterogeneity (I2 = 99.14). As a second-line treatment for csDMARD failed RA, JAK-i is cost-effective than csDMARD/bDMARD with a pooled INB of $23,144 (74.1-46,214) and high heterogeneity (I2 = 99.67). But on a separate analysis JAK-i as second-line treatment is not cost-effective than TNF-a-i (INBp = $25,813, -5,714 to 57,340). However, leave-one-out analysis found that omitting a single outlier makes JAK-i cost-effective. Further, JAK-i is not cost-effective as a third-line treatment for csDMARD-TNF-a-I failed RA, compared to csDMARDs/bDMARDs with INBp $26,157 (-7,284 to 59,598). Conclusion: Meta-analysis suggests that JAK-i is cost-effective when used after csDMARD failure but not cost-effective when used after csDMARD-TNF-a-i failure with low certainty of evidence. Clinical Trial Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021222541, identifier CRD42021222541.

Is State-Wise Healthcare Budget Allocation Consistent With the Disease Burden in India? A Quinquennial Account (2015-2019).

Introduction: Evidence-based resource allocation may help to achieve immense health gains in resource-limited settings like India. Understanding healthcare expenditure and the corresponding disease burden could provide insights to plan optimal allocation of limited resources. Hence, we aimed to investigate the status and trends of state-wise healthcare budget allocation and the corresponding disease burden. Methods: We retrieved state-wise healthcare budget allocation information in India for the years 2015 to 2019. Corresponding state-wise disability-adjusted-life-year (DALY) estimates from the Global Burden of Disease, injuries, and Risk Factors Study (GBD) was used to measure disease burden. The allocated budget (in rupees) per DALY was calculated for overall, communicable, and non-communicable diseases (NCDs). Descriptive statistics, correlation and graphical representations were used to identify and evaluate the trends and relationships between state-wise health budget allocation and disease burden. Results: The allocated budget per DALY in 2019 was highest for Goa ( 34,260 or US$ 486.66) and lowest for Bihar ( 2,408 or US $ 34.20). Smaller, less populous states had higher budget allocations per DALY than larger states. Health budget allocation had an inverse relationship with infectious diseases and an identical linear relationship with NCDs. Most state-wise health budget allocations, as well as total disease burden, increased over the years except for Assam, Karnataka, and Himachal Pradesh. Also, such trends are not similar for the injuries and NCD disease burden. Discussion: The health budget allocation is variable across states as well as between infectious and NCDs. The current increase in the allocated budget is incongruent with the increasing disease burden. There is a need for rapid expansion of healthcare resource allocation guided by evidence in India.

Cost-effectiveness of Ezetimibe plus statin lipid-lowering therapy: A systematic review and meta-analysis of cost-utility studies.

In addition to statin therapy, Ezetimibe, a non-statin lipid-modifying agent, is increasingly used to reduce low-density lipoprotein cholesterol and atherosclerotic cardiovascular disease risk. Literature suggests the clinical effectiveness of Ezetimibe plus statin (EPS) therapy; however, primary evidence on its economic effectiveness is inconsistent. Hence, we pooled incremental net benefit to synthesise the cost-effectiveness of EPS therapy. We identified economic evaluation studies reporting outcomes of EPS therapy compared with other lipid-lowering therapeutic agents or placebo by searching PubMed, Embase, Scopus, and Tufts Cost-Effective Analysis registry. Using random-effects meta-analysis, we pooled Incremental Net Benefit (INB) in the US $ with a 95% confidence interval (CI). We used the modified economic evaluations bias checklist and GRADE quality assessment for quality appraisal. The pooled INB from twenty-one eligible studies showed that EPS therapy was significantly cost-effective compared to other lipid-lowering therapeutic agents or placebo. The pooled INB (95% CI) was $4,274 (621 to 7,927), but there was considerable heterogeneity (I2 = 84.21). On subgroup analysis EPS therapy is significantly cost-effective in high-income countries [$4,356 (621 to 8,092)], for primary prevention [$4,814 (2,523 to 7,106)], and for payers' perspective [$3,255 (571 to 5,939)], and from lifetime horizon [$4,571 (746 to 8,395)]. EPS therapy is cost-effective compared to other lipid-lowering therapeutic agents or placebo in high-income countries and for primary prevention. However, there is a dearth of evidence from lower-middle-income countries and the societal perspective.

Meta-analysis of economic evaluation studies: data harmonisation and methodological issues.

BACKGROUND: In the context of ever-growing health expenditure and limited resources, economic evaluations aid in making evidence-informed policy decisions. Cost-utility analysis (CUA) is often used, and CUA data synthesis is also desirable, but methodological issues are challenged. Hence, we aim to provide a step-by-step process to prepare the CUA data for meta-analysis. METHODS: Data harmonisation methods were constructed specifically considering CUA methodology, including inconsistent reports, economic parameters, heterogeneity (i.e., country's income, time horizon, perspective, modelling approaches, currency, willingness to pay). An incremental net benefit (INB) and its variance were estimated and pooled across studies using a basic meta-analysis by COMER. RESULTS: Five scenarios show how to obtain INB and variance with various reported data: Study reports the mean and variance (Scenario 1) or 95% confidence interval (Scenario 2) of ΔC, ΔE, and ICER for INB/variance calculations. Scenario 3: ΔC, ΔE, and variances are available, but not for the ICER; a Monte Carlo was used to simulate ΔC and ΔE data, variance and covariance can be then estimated leading INB calculation. Scenario-4: Only the CE plane was available, ΔC and ΔE data can be extracted; means of ΔC, ΔE, and variance/covariance can be estimated accordingly, leading to INB/variance estimates. Scenario-5: Only mean cost/outcomes and ICER are available but not for variance and the CE-plane. A variance INB can be borrowed from other studies which are similar characteristics, including country income, ICERs, intervention-comparator, time period, country region, and model type and inputs (i.e., discounting, time horizon). CONCLUSION: Out data harmonisation and meta-analytic methods should be useful for researchers for the synthesis of economic evidence to aid policymakers in decision making.

Incremental net benefit of cholecystectomy compared with alternative treatments in people with gallstones or cholecystitis: a systematic review and meta-analysis of cost-utility studies.

INTRODUCTION: Cholecystectomy is a standard treatment in the management of symptomatic gallstone disease. Current literature has contradicting views on the cost-effectiveness of different cholecystectomy treatments. We have conducted a systematic reappraisal of literature concerning the cost-effectiveness of cholecystectomy in management of gallstone disease. METHODS: We systematically searched for economic evaluation studies from PubMed, Embase and Scopus for eligible studies from inception up to July 2020. We pooled the incremental net benefit (INB) with a 95% CI using a random-effects model. We assessed the heterogeneity using the Cochrane-Q test, I2 statistic. We have used the modified economic evaluation bias (ECOBIAS) checklist for quality assessment of the selected studies. We assessed the possibility of publication bias using a funnel plot and Egger's test. RESULTS: We have selected 28 studies for systematic review from a search that retrieved 8710 studies. Among them, seven studies were eligible for meta-analysis, all from high-income countries (HIC). Studies mainly reported comparisons between surgical treatments, but non-surgical gallstone disease management studies were limited. The early laparoscopic cholecystectomy (ELC) was significantly more cost-effective compared with the delayed laparoscopic cholecystectomy (DLC) with an INB of US$1221 (US$187 to US$2255) but with high heterogeneity (I2=73.32%). The subgroup and sensitivity analysis also supported that ELC is the most cost-effective option for managing gallstone disease or cholecystitis. CONCLUSION: ELC is more cost-effective than DLC in the treatment of gallstone disease or cholecystitis in HICs. There was insufficient literature on comparison with other treatment options, such as conservative management and limited evidence from other economies. PROSPERO REGISTRATION NUMBER: CRD42020194052.

Health-related quality of life among COVID-19 individuals: A cross-sectional study in Tamil Nadu, India.

INTRODUCTION: The EQ-5D-5L questionnaire is a tool that is a very generic and preference-based instrument to describe the health-related quality of life. We have generated the stratified index utility value for the Tamil Nadu population and compared the utility values based on socio-demographic and clinical characteristics. METHODS: We conducted a community-based analytical cross-sectional study using telephonic interviews from November 2020 till December 2020 among individuals aged 18 years and above who were infected by the coronavirus confirmed with an RT-PCR within 30 days in Tamil Nadu State. EQ-5D-5L profile, socio-demographic and clinical characteristics of the study participants were collected and analysed. RESULTS: We interviewed 372 participants, with 57.5% were males, and their mean age was 44.5 ± 15.3 years. About 40% of participants reported as having comorbidities, such as diabetes (19.4%), hypertension (12.4%), heart disease (2.4%), kidney disease (0.8%) and others. The mean EQ-5D utility score was 0.925 ± 0.150, and the mean EQ-VAS was 90.68 ± 11.81. Overall, men had a higher utility value (0.938 ± 0.130) than women, (0.907 ± 0.170). Individuals with comorbidities, requiring longer hospitalisation were having lower utility scores than their counterparts. CONCLUSION: We report the EQ-5D-5L utility values for the COVID-19 illness. These values would help to estimate quality-adjusted life years in health economic evaluation studies.

Air pollution attributed disease burden and economic growth in India: Estimating trends and inequality between states.

Background: Air pollution is one of the major contributors to the disease burden in India after malnutrition. We examined the relation, and state-wise disparities in air pollution attributed to disease burden (APADB) concerning gross state domestic product (GSDP) and growth in motor vehicles in India. Methods: We retrieved disability-adjusted life year (DALY) estimates for India due to air pollution from the Global Burden of Disease Studies, injuries, and Risk Factors Study (GBD). We examined the association between APADB with GSDP and the growth in the number of registered motor vehicles in India during the 2011 to 2019 period. Concentration indices and Lorenz curves were used to explore the variation in APADB across individual states. Findings: Except for a few states, APADB is inversely proportional to GSDP. Growth in motor vehicles was also negatively correlated with the APADB in n=19 states. The concentration index explained a 47% inequality in APADB between individual states and exhibited a decline (45%) during 2019 compared to 2011. The unevenness in APADB among Indian states is evident from the analysis as the states occupying the 6th or 7th decile and above in terms of GDP, urbanization and population contribute more than 60 per cent of the total APADB. Interpretation: The APADB is inversely correlated with GSDP for most of the states, and the negative correlations were conspicuous when APADB per 100,000 population was analysed. The concentration index and Lorenz revealed the presence of APADB inequality between states in terms of GSDP, population, urbanisation, and total factories. Funding: Not applicable.

Electronic versus paper-based data collection for conducting health-care research: A cost-comparison analysis.

Background: Containing expenditure and efficient resource use is essential to limit the increasing costs of health research. Electronic data collection (EDC) is thought to reduce the costs compared to paper-based data collection (PDC). Objectives: As economic evidence in this area is scanty, especially in low- and middle-income countries, the objectives of the study are to perform an economic evaluation and compare the cost between EDC and PDC. Methods: A cost-comparison study was conducted to compare between EDC and PDC from the institutional perspective for the year 2018, based on a community-based survey. Step-down cost accounting was adopted with a bottom-up approach for cost estimation. Total and unit costs were estimated with the base case comparison between EDC and PDC while using SPSS software (e-SPSS and p-SPSS, respectively). We conducted scenario analyses based on the usage of different software, R and STATA for both EDC and PDC (e-R, p-R, e-STATA, and p-STATA, respectively). One-way and probabilistic sensitivity analysis (PSA) was performed to examine the robustness of the observed results. Results: In the base-case analysis, total costs of EDC and PDC were ₹72,617 ($1060.9) and 87,717 ($1281.5), respectively, with estimated cost reduction of ₹15,100 ($220.6). In other scenarios, the estimated cost reduction for e-R, e-STATA, p-R, p-STATA was ₹-274 ($4.0), 98 ($1.4), 14826 ($216.6), and 15,002 ($219.2), respectively, when compared to EDC-SPSS. On one-way and PSA, the results of the cost-comparison analysis were robust. Conclusion: EDC minimizes institutional cost for conducting health research. This finding will help researchers in efficiently planning for the budget for their research.

Economic evaluation of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) for stroke prevention in patients with atrial fibrillation: a systematic review and meta-analysis.

OBJECTIVES: To assess cost-effectiveness of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF) by pooling incremental net benefits (INBs). DESIGN: Systematic review and meta-analysis. SETTING: We searched PubMed, Scopus and Centre for Evaluation of Value and Risks in Health Registry from inception to December 2019. PARTICIPANTS: Patients with AF. MAIN OUTCOME MEASURES: The INB was defined as a difference of incremental effectiveness multiplied by willing to pay threshold minus the incremental cost; a positive INB indicated favour treatment. These INBs were pooled (stratified by level of country income, perspective, time-horizon, model types) with a random-effects model if heterogeneity existed, otherwise a fixed effects model was applied. Heterogeneity was assessed using Q test and I2 statistic. Risk of bias was assessed using the economic evaluations bias (ECOBIAS) checklist. RESULTS: A total of 100 eligible economic evaluation studies (224 comparisons) were included. For high-income countries (HICs) from a third-party payer (TPP) perspective, the pooled INBs for DOAC versus VKA pairs were significantly cost-effective with INBs (95% CI) of $6632 ($2961.67 to $10 303.72; I2=59.9%), $6353.24 ($4076.03 to $8630.45; I2=0%), $7664.58 ($2979.79 to $12 349.37; I2=0%) and $8573.07 ($1877.05 to $15 269.09; I2=0%) for dabigatran, apixaban, rivaroxaban and edoxaban relative to VKA, respectively but only dabigatran was significantly cost-effective from societal perspective (SP) with an INB of $11 746.96 ($2429.34 to $21 064.59; I2=52.4%). The pooled INBs of all comparisons for upper-middle income countries (UMICs) were not significantly cost-effective. The ECOBIAS checklist indicated that risk of bias was mostly low for most items with the exception of five items which should be less influenced on pooling INBs. CONCLUSIONS: Our meta-analysis provides comprehensive economic evidence that allows policy makers to generalise cost-effectiveness data to their local context. All DOACs may be cost-effective compared with VKA in HICs with TPP perspective. The pooling results produced moderate to high heterogeneity particularly in UMICs. Further studies are required to inform UMICs with SP. PROSPERO REGISTERATION NUMBER: CRD 42019146610.

Incremental net benefit of lipid-lowering therapy with PCSK9 inhibitors: a systematic review and meta-analysis of cost-utility studies.

INTRODUCTION: Proprotein convertase subtilisin/kexin 9 inhibitors (PCSK9i) are monoclonal antibodies that lower lipid levels. Although several cardiovascular outcome trials reported the effectiveness of PCSK9i, the evidence on cost-effectiveness is mixed. We systematically reviewed the evidence and synthesized incremental net benefit (INB) to quantify pooled cost-effectiveness. METHODS: We systematically searched for full economic evaluation studies reporting outcomes of PCSK9i compared with other lipid-lowering pharmacotherapies. We searched PubMed, Embase, Scopus, and Tufts Registry for eligible studies up to August 2021, adhering to preferred reporting items for systematic reviews and meta-analyses guidelines. We pooled INB in US$ with a 95% confidence interval using a random-effects model. We assessed heterogeneity using the Cochran Q test and I2 statistics. We used the modified economic evaluations bias (ECOBIAS) checklist to evaluate the quality of selected studies. RESULTS: Twenty-three studies were eligible, mainly from high-income countries (HIC). The pooled INB (INBp) of PCSK9i versus other lipid-lowering pharmacotherapies were estimated from n = 24 comparisons, with high heterogeneity (I2 = 99.99). The INBp (95% CI) was $ - 78,207 (- 120,422; - 35,993) or € - 52,526 (- 80,879; - 24,174) (conversion factor 1 US$ = 0.67€) which shows that PCSK9i was not significantly cost-effective when compared to other standard therapies. On subgroup analysis PCSK9i was significantly not cost-effective [$ - 23,672 (- 24,061; - 23,282)] compared to other lipid-lowering pharmacotherapies in HICs, upper-middle-income countries [$ - 158,412 (- 241,738; - 75,086)] or when the target population was CVD [$ - 109,343 (- 158,968; - 59,717)]; and for treatment subgroup: against placebo or no treatment [$ - 79,018 (- 79,649; - 78,388 PCSK9)] and standard statin therapies [$ - 131,833 (- 173,449; - 90,216)]. The sensitivity analysis revealed that the findings are not robust for HICs and the treatment subgroups. CONCLUSION: PCSK9 inhibitors are not cost-effective compared to other lipid-lowering pharmacotherapies in HICs. Further, current pieces of evidence are predominantly from HICs with largely lacking evidence from other economies. PROSPERO REGISTRATION: ID CRD42020206043.