First-line Treatment with Empagliflozin and Metformin Combination Versus Standard Care for Patients with Type 2 Diabetes Mellitus and Cardiovascular Disease in Qatar. A Cost-Effectiveness Analysis

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown to reduce cardiovascular events and mortality in patients with type 2 diabetes mellitus (T2DM), but they are currently not used as first-line therapy in clinical practice. This study sought to evaluate the cost-effectiveness of first-line empagliflozin plus standard care for patients with newly diagnosed T2DM and existing cardiovascular disease (CVD). A decision-analytic Markov model with one-year cycles and a lifetime time horizon was developed from the perspective of the Qatari healthcare system to compare first-line empagliflozin combined with metformin versus metformin monotherapy for patients aged 50 to 79 years with T2DM and existing CVD. Two health states were considered: ‘Alive with CVD and T2DM’ and ‘Dead’. Patients could experience non-fatal myocardial infarction, non-fatal stroke, hospitalization for heart failure, hospitalization for unstable angina, and cardiovascular or non-cardiovascular death. Model inputs were ascertained from published and publicly available sources in Qatar. Costs and outcomes were discounted at 3% per annum. Sensitivity analyses were conducted to evaluate parameter uncertainty. The model predicted that adding empagliflozin to current standard care led to additional 1.9 years of life saved (YoLS) and 1.5 quality-adjusted life year (QALYs) per person, and an incremental cost of QAR 56,869 (USD 15,619), which equated to an incremental cost-effectiveness ratio of QAR 30,675 (USD 8,425) per YoLS and QAR 39,245 (USD 10,779) per QALY. Sensitivity analyses showed the findings to be robust. First-line empagliflozin combined with metformin appears to be a cost-effective therapeutic option for patients with T2DM and CVD

Cost-Effectiveness of Non-Statin Lipid-Modifying Agents for Primary and Secondary Prevention of Cardiovascular Disease among Patients with Type 2 diabetes mellitus: A Systematic Review

Background: Non-statin therapies (NSTs) have been shown to provide additional benefits for cardiovascular risk reduction among patients with type 2 diabetes mellitus (T2DM), but their economic merits have not been confirmed. The objective of this systematic review is to evaluate the cost-effectiveness of NSTs for primary and secondary prevention of cardiovascular disease (CVD) in T2DM patients. 1 Methods: A literature search was systematically performed using MeSH terms (Table 1) from January 1990 to January 2021 in ten databases (e.g. MEDLINE, PubMed, and EconLit). Two reviewers independently screened the included studies that evaluated the cost-effectiveness of NSTs versus any comparator. Quality of Health Economic Studies (QHES) checklist was used for quality assessment. 2 Cost outputs were adapted to 2019 United States dollars (USD) to facilitate comparisons between studies. 3 Results: The search identified 21,182 records. Of which, 10,781 records were screened based on the title and abstract, and 185 articles based on the full text (Figure 1). After a full-text review, 12 studies were included in this study, where eight studies evaluated ezetimibe, four evaluated Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors, two evaluated fenofibrate, one evaluated nicotinic acid, and one evaluated extended-release niacin/laropiprant (ER-ERN/LRPT). Six out of eight studies considered ezetimibe plus statin to be a cost-effective therapy for patients with T2DM and with or without CVD, three out of four studies suggested that PCSK9 inhibitors were not cost-effective. Fenofibrate, nicotinic acid, and ER- ERN/LRPT were cost-effective. Based on QHES, the majority of economic evaluations had good quality of reporting. The ICERs were consistent in the majority of studies after adaptation to 2019 USD values. 1-3 Conclusion: The systematic review demonstrated that most cost-effectiveness studies considered NSTs to be cost-effective compared with standard care but not PCSK9 inhibitors for primary and secondary prevention of CVD in T2DM patients.qscienc

Projecting the Health and Economic Burden of Cardiovascular Disease Among People with Type 2 Diabetes, 2022–2031

Objective: The aim was to project the health and economic outcomes of cardiovascular disease (CVD) among people with type 2 diabetes from Australian public healthcare and societal perspectives over the next decade. Methods: A dynamic multistate model with yearly cycles was developed to project cardiovascular events among Australians with type 2 diabetes aged 40–89 years from 2022 to 2031. CVD risk (myocardial infarction [MI] and stroke) in the type 2 diabetes population was estimated using the 2013 pooled cohort equation, and recurrent cardiovascular event rates in the type 2 diabetes with established CVD population were obtained from the global Reduction of Atherothrombosis for Continued Health (REACH) registry. Costs and utilities were derived from published sources. Outcomes included fatal and non-fatal MI and stroke, years of life lived, quality-adjusted life years (QALYs), total healthcare costs, and total productivity losses. The annual discount rate was 5%, applied to outcomes and costs. Results: Between 2022 and 2031, a total of 83,618 non-fatal MIs (95% uncertainty interval [UI] 83,170–84,053) and 58,774 non-fatal strokes (95% UI 58,458–59,013) were projected. Total years of life lived and QALYs (discounted) were projected to be 9,549,487 (95% UI 9,416,423–9,654,043) and 6,632,897 (95% UI 5,065,606–7,591,679), respectively. Total healthcare costs and total lost productivity costs (discounted) were projected to be 9.59 billion Australian dollars (AU$) (95$9.07 billion (95% UI 663.53 million–33.19 billion), respectively. Conclusions: CVD in people with type 2 diabetes will substantially impact the Australian healthcare system and society over the next decade. Future work to investigate different strategies to optimize the control of risk factors for the prevention and treatment of CVD in type 2 diabetes in Australia is warranted

The effectiveness of non-pharmaceutical interventions in reducing SARS-CoV-2 transmission and COVID-19 incidence and mortality:systematic review and meta-analysis

OBJECTIVE: To review the evidence on the effectiveness of public health measures in reducing the incidence of covid-19, SARS-CoV-2 transmission, and covid-19 mortality. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, CINAHL, Biosis, Joanna Briggs, Global Health, and World Health Organization COVID-19 database (preprints). ELIGIBILITY CRITERIA FOR STUDY SELECTION: Observational and interventional studies that assessed the effectiveness of public health measures in reducing the incidence of covid-19, SARS-CoV-2 transmission, and covid-19 mortality. MAIN OUTCOME MEASURES: The main outcome measure was incidence of covid-19. Secondary outcomes included SARS-CoV-2 transmission and covid-19 mortality. DATA SYNTHESIS: DerSimonian Laird random effects meta-analysis was performed to investigate the effect of mask wearing, handwashing, and physical distancing measures on incidence of covid-19. Pooled effect estimates with corresponding 95% confidence intervals were computed, and heterogeneity among studies was assessed using Cochran’s Q test and the I(2) metrics, with two tailed P values. RESULTS: 72 studies met the inclusion criteria, of which 35 evaluated individual public health measures and 37 assessed multiple public health measures as a “package of interventions.” Eight of 35 studies were included in the meta-analysis, which indicated a reduction in incidence of covid-19 associated with handwashing (relative risk 0.47, 95% confidence interval 0.19 to 1.12, I(2)=12%), mask wearing (0.47, 0.29 to 0.75, I(2)=84%), and physical distancing (0.75, 0.59 to 0.95, I(2)=87%). Owing to heterogeneity of the studies, meta-analysis was not possible for the outcomes of quarantine and isolation, universal lockdowns, and closures of borders, schools, and workplaces. The effects of these interventions were synthesised descriptively. CONCLUSIONS: This systematic review and meta-analysis suggests that several personal protective and social measures, including handwashing, mask wearing, and physical distancing are associated with reductions in the incidence covid-19. Public health efforts to implement public health measures should consider community health and sociocultural needs, and future research is needed to better understand the effectiveness of public health measures in the context of covid-19 vaccination. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020178692

Considering equity and cost-effectiveness in assessing a parenting intervention to promote early childhood development in rural Vietnam

Considering equity in early childhood development (ECD) is important to ensure healthy development for every child. Equity-informative cost-effectiveness analysis can further guide decision makers to maximize outcomes with limited resources while promoting equity. This cost-effectiveness study aimed to examine the equity impacts of a multicomponent ECD intervention in rural Vietnam. We estimated the cost-effectiveness of the intervention with a 30-month time horizon from the service provider and household perspectives with equity considerations. Data were from a cluster-randomized controlled trial comparing the intervention with the local standard of care. The incremental cost-effectiveness ratios (ICERs) per child cognitive development score gained were estimated by household wealth quintile and maternal education level, adjusted for cluster effects and baseline characteristics such as maternal parity and age. A 3% discount rate was applied to costs, and non-parametric cluster bootstrapping was used to examine uncertainty around ICERs. Children in the intervention had higher cognitive development scores than those in the control arm across all subgroups. Based on intervention recurrent cost, the ICER per cognitive development score gained was lower in children from the poorest quintile (−US$6) compared to those from the richest quintile (US$16). Similarly, the ICER per cognitive development score gained was lower in children whose mothers had the lowest education level (−US$0.02) than those with mothers who had the highest education level (US$7). Even though our findings should be interpreted with caution due to the insufficient study power, the findings suggest that the intervention could promote equity while improving child cognitive development with greater cost-effectiveness in disadvantaged groups

Combined population genomic screening for three high-risk conditions in Australia: a modelling study

BACKGROUND: No previous health-economic evaluation has assessed the impact and cost-effectiveness of offering combined adult population genomic screening for mutliple high-risk conditions in a national public healthcare system. METHODS: This modeling study assessed the impact of offering combined genomic screening for hereditary breast and ovarian cancer, Lynch syndrome and familial hypercholesterolaemia to all young adults in Australia, compared with the current practice of clinical criteria-based testing for each condition separately. The intervention of genomic screening, assumed as an up-front single cost in the first annual model cycle, would detect pathogenic variants in seven high-risk genes. The simulated population was 18–40 year-olds (8,324,242 individuals), modelling per-sample test costs ranging AU$100–$1200 (base-case AU$200) from the year 2023 onwards with testing uptake of 50 FINDINGS: Over the population lifetime (to age 80 years), the model estimated that genomic screening per-100,000 individuals would lead to 747 QALYs gained by preventing 63 cancers, 31 CHD cases and 97 deaths. In the total model population, this would translate to 31,094 QALYs gained by preventing 2612 cancers, 542 non-fatal CHD events and 4047 total deaths. At AU$200 per-test, genomic screening would require an investment of AU$832 million for screening of 50$23,926 (∼£12,050/€14,110/US$15,345) per QALY gained over the status quo. In scenario analysis with 3$4758/QALY was obtained. Sensitivity analysis for the base case indicated that combined genomic screening would be cost-effective under 70% of simulations, cost-saving under 25% and not cost-effective under 5%. Threshold analysis showed that genomic screening would be cost-effective under the AU$50,000/QALY willingness-to-pay threshold at per-test costs up to AU$325 (∼£164/€192/US$208). INTERPRETATION: Our findings suggest that offering combined genomic screening for high-risk conditions to young adults would be cost-effective in the Australian public healthcare system, at currently realistic testing costs. Other matters, including psychosocial impacts, ethical and societal issues, and implementation challenges, also need consideration. FUNDING: Australian Government, Department of Health, Medical Research Future Fund, Genomics Health Futures Mission (APP2009024). National Heart Foundation Future Leader Fellowship (102604)

The burden and trend of diseases and their risk factors in Australia, 1990 – 2019 : a systematic analysis for the Global Burden of Disease Study 2019

Background: A comprehensive understanding of temporal trends in the disease burden in Australia is lacking, and these trends are required to inform health service planning and improve population health. We explored the burden and trends of diseases and their risk factors in Australia from 1990 to 2019 through a comprehensive analysis of the Global Burden of Disease Study (GBD) 2019. Methods: In this systematic analysis for GBD 2019, we estimated all-cause mortality using the standardised GBD methodology. Data sources included primarily vital registration systems with additional data from sample registrations, censuses, surveys, surveillance, registries, and verbal autopsies. A composite measure of health loss caused by fatal and non-fatal disease burden (disability-adjusted life-years [DALYs]) was calculated as the sum of years of life lost (YLLs) and years of life lived with disability (YLDs). Comparisons between Australia and 14 other high-income countries were made. Findings: Life expectancy at birth in Australia improved from 77·0 years (95% uncertainty interval [UI] 76·9–77·1) in 1990 to 82·9 years (82·7–83·1) in 2019. Between 1990 and 2019, the age-standardised death rate decreased from 637·7 deaths (95% UI 634·1–641·3) to 389·2 deaths (381·4–397·6) per 100 000 population. In 2019, non-communicable diseases remained the major cause of mortality in Australia, accounting for 90·9% (95% UI 90·4–91·9) of total deaths, followed by injuries (5·7%, 5·3–6·1) and communicable, maternal, neonatal, and nutritional diseases (3·3%, 2·9–3·7). Ischaemic heart disease, self-harm, tracheal, bronchus, and lung cancer, stroke, and colorectal cancer were the leading causes of YLLs. The leading causes of YLDs were low back pain, depressive disorders, other musculoskeletal diseases, falls, and anxiety disorders. The leading risk factors for DALYs were high BMI, smoking, high blood pressure, high fasting plasma glucose, and drug use. Between 1990 and 2019, all-cause DALYs decreased by 24·6% (95% UI 21·5–28·1). Relative to similar countries, Australia's ranking improved for age-standardised death rates and life expectancy at birth but not for YLDs and YLLs between 1990 and 2019. Interpretation: An important challenge for Australia is to address the health needs of people with non-communicable diseases. The health systems must be prepared to address the increasing demands of non-communicable diseases and ageing

Promoting early childhood development in Viet Nam: cost-effectiveness analysis alongside a cluster-randomised trial

Economic evaluations are critical to ensure effective resource use to implement and scale up child development interventions. This study aimed to estimate the cost-effectiveness of a multicomponent early childhood development intervention in rural Viet Nam. We did a cost-effectiveness study alongside a cluster-randomised trial with a 30-month time horizon. The study included 669 mothers from 42 communes in the intervention group, and 576 mothers from 42 communes in the control group. Mothers in the intervention group attended Learning Clubs sessions from mid-pregnancy to 12 months after delivery. The primary outcomes were child cognitive, language, motor, and social-emotional development at age 2 years. In this analysis, we estimated the incremental cost-effectiveness ratios (ICERs) of the intervention compared with the usual standard of care from the service provider and household perspectives. We used non-parametric bootstrapping to examine uncertainty, and applied a 3% discount rate. The total intervention cost was US$169 898 (start-up cost$133 692 and recurrent cost $36 206). The recurrent cost per child was$58 (1 341 741 Vietnamese dong). Considering the recurrent cost alone, the base-case ICER was $14 and mean ICER of 1000 bootstrap samples was$14 (95% CI -0·48 to 30) per cognitive development score gained with a 3% discount rate to costs. The ICER per language and motor development score gained was $22 and$20, respectively, with a 3% discount rate to costs. The intervention was cost-effective: the ICER per child cognitive development score gained was 0·5% of Viet Nam's gross domestic product per capita, alongside other benefits in language and motor development. This finding supports the scaling up of this intervention in similar socioeconomic settings. Australian National Health and Medical Research Council and Grand Challenges Canada. For the Vietnamese translation of the abstract see Supplementary Materials section

Cost-effectiveness of everolimus-eluting versus bare-metal stents in ST-segment elevation myocardial infarction: An analysis from the EXAMINATION randomized controlled trial.

BACKGROUND: Use of everolimus-eluting stents (EES) has proven to be clinically effective and safe in patients with ST-segment elevation myocardial infarction but it remains unclear whether it is cost-effective compared to bare-metal stents (BMS) in the long-term. We sought to assess the cost-effectiveness of EES versus BMS based on the 5-year results of the EXAMINATION trial, from a Spanish health service perspective. METHODS: Decision analysis of the use of EES versus BMS was based on the patient-level clinical outcome data of the EXAMINATION trial. The analysis adopted a lifelong time horizon, assuming that long-term survival was independent of the initial treatment strategy after the end of follow-up. Life-expectancy, health-state utility scores and unit costs were extracted from published literature and publicly available sources. Non-parametric bootstrapping was combined with probabilistic sensitivity analysis to co-assess the impact of patient-level variation and parameter uncertainty. The main outcomes were total costs and quality-adjusted life-years. The incremental cost-effectiveness ratio was expressed as cost per quality-adjusted life-years gained. Costs and effects were discounted at 3%. RESULTS: The model predicted an average survival time in patients receiving EES and BMS of 10.52 and 10.38 undiscounted years, respectively. Over the life-long time horizon, the EES strategy was ¿430 more costly than BMS (¿8,305 vs. ¿7,874), but went along with incremental gains of 0.10 quality-adjusted life-years. This resulted in an average incremental cost-effectiveness ratio over all simulations of ¿3,948 per quality-adjusted life-years gained and was below a willingness-to-pay threshold of ¿25,000 per quality-adjusted life-years gained in 86.9% of simulation runs. CONCLUSIONS: Despite higher total costs relative to BMS, EES appeared to be a cost-effective therapy for ST-segment elevation myocardial infarction patients due to their incremental effectiveness. Predicted incremental cost-effectiveness ratios were below generally acceptable threshold values