Evaluating Health and Well-Being Returns on Investment in a Cancer Biobank.

Objectives: To evaluate the population health returns from investment in the Victorian Cancer Biobank (VCB), a research consortium including five hospital-integrated sample repositories located in Melbourne, Australia. Methods: This economic evaluation assigned monetary values to the health gains attributable to VCB-supported research. These were then compared with the total investment in VCB infrastructure since inception (2006-2022) to determine the return on investment (ROI). A time lag of 40 years was incorporated, recognizing the delay from investment to impact in scientific research. Health gains were therefore measured for the years 2046-2066, with a 3% discount rate applied. Health gains were measured in terms of disability-adjusted life years (DALYs) attributable to VCB-associated research, with monetary cost assigned via the standardized value of a statistical life year (AU$227,000). The age-standardized DALY rate attributable to cancer was modeled for two standpoints (1) extrapolating the current decreasing trajectory and (2) assuming nil future improvement from current rates, with 33% of the difference attributed to scientific innovation. The proportion of the aggregate health gain attributable to VCB-supported research was estimated from the number of VCB-credited scientific publications as a proportion of total oncology publications over the same period. Results: The AU$32,628,016 of public funding invested in VCB activities over the years 2006-2022 is projected to generate AU$84,561,373 in total (discounted) savings. ROI was AU$1.59 for each AU$1 invested. Conclusions: The VCB offers a strong ROI in terms of impacts on health, justifying the expenditure of public funds and supporting the use of biobanks to advance scientific research.

Cost-Effectiveness of Screening Strategies for Familial Hypercholesterolaemia: An Updated Systematic Review.

BACKGROUND: OBJECTIVE: This study aimed to systematically synthesise the cost-effectiveness of screening strategies to detect heterozygous familial hypercholesterolemia (FH). METHODS: We searched seven databases from inception to 2 February , 2023, for eligible cost-effective analysis (CEA) that evaluated screening strategies for FH versus the standard care for FH detection. Independent reviewers performed the screening, data extraction and quality evaluation. Cost results were adapted to 2022 US dollars (US$) to facilitate comparisons between studies using the same screening strategies. Cost-effectiveness thresholds were based on the original study criteria. RESULTS: A total of 21 studies evaluating 62 strategies were included in this review, most of the studies (95%) adopted a healthcare perspective in the base case, and majority were set in high-income countries. Strategies analysed included cascade screening (23 strategies), opportunistic screening (13 strategies), systematic screening (11 strategies) and population-wide screening (15 strategies). Most of the strategies relied on genetic diagnosis for case ascertainment. The most common comparator was no screening, but some studies compared the proposed strategy versus current screening strategies or versus the best next alternative. Six studies evaluated screening in children while the remaining were targeted at adults. From a healthcare perspective, cascade screening was cost-effective in 78% of the studies [cost-adapted incremental cost-effectiveness ratios (ICERs) ranged from dominant to 2022 US$ 104,877], opportunistic screening in 85% (ICERs from US$4959 to US$41,705), systematic screening in 80% (ICERs from US$2763 to US$69,969) and population-wide screening in 60% (ICERs from US$1484 to US$223,240). The most common driver of ICER identified in the sensitivity analysis was the long-term cost of lipid-lowering treatment. CONCLUSIONS: Based on reported willingness to pay thresholds for each setting, most CEA studies concluded that screening for FH compared with no screening was cost-effective, regardless of the screening strategy. Cascade screening resulted in the largest health benefits per person tested.

Lipid-Lowering Strategies for Primary Prevention of Coronary Heart Disease in the UK: A Cost-Effectiveness Analysis.

AIM: We aimed to assess the cost effectiveness of four different lipid-lowering strategies for primary prevention of coronary heart disease initiated at ages 30, 40, 50, and 60 years from the UK National Health Service perspective. METHODS: We developed a microsimulation model comparing the initiation of a lipid-lowering strategy to current standard of care (control). We included 458,692 participants of the UK Biobank study. The four lipid-lowering strategies were: (1) low/moderate-intensity statins; (2) high-intensity statins; (3) low/moderate-intensity statins and ezetimibe; and (4) inclisiran. The main outcome was the incremental cost-effectiveness ratio for each lipid-lowering strategy compared to the control, with 3.5% annual discounting using 2021 GBP (£); incremental cost-effectiveness ratios were compared to the UK willingness-to-pay threshold of £20,000-£30,000 per quality-adjusted life-year. RESULTS: The most effective intervention, low/moderate-intensity statins and ezetimibe, was projected to lead to a gain in quality-adjusted life-years of 0.067 per person initiated at 30 and 0.026 at age 60 years. Initiating therapy at 40 years of age was the most cost effective for all lipid-lowering strategies, with incremental cost-effectiveness ratios of £2553 (95% uncertainty interval: 1270, 3969), £4511 (3138, 6401), £11,107 (8655, 14,508), and £1,406,296 (1,121,775, 1,796,281) per quality-adjusted life-year gained for strategies 1-4, respectively. Incremental cost-effectiveness ratios were lower for male individuals (vs female individuals) and for people with higher (vs lower) low-density lipoprotein-cholesterol. For example, low/moderate-intensity statin use initiated from age 40 years had an incremental cost-effectiveness ratio of £5891 (3822, 9348), £2174 (772, 4216), and was dominant (i.e. cost saving; -2,760, 350) in female individuals with a low-density lipoprotein-cholesterol of ≥ 3.0, ≥ 4.0 and ≥ 5.0 mmol/L, respectively. Inclisiran was not cost effective in any sub-group at its current price. CONCLUSIONS: Low-density lipoprotein-cholesterol lowering from early ages is a more cost-effective strategy than late intervention and cost effectiveness increased with the increasing lifetime risk of coronary heart disease.

Health economics of detection and treatment of children with familial hypercholesterolemia: to screen or not to screen is no longer the question.

PURPOSE OF REVIEW: Heterozygous familial hypercholesterolemia (HeFH) is one of the most common monogenic disorders and is safely treatable with lipid-lowering medication. However, most individuals with HeFH remain untreated and undetected, especially in paediatric populations where the potential for long-term therapeutic benefit is higher. Here, we review the recent literature on health economic outcomes for the detection and management of FH in children. RECENT FINDINGS: A targeted literature review identified eight studies evaluating detection and management strategies for paediatric FH populations in the last 25 years. Most studies conducted modelled cost-effectiveness analyses to understand the long-term impact of these strategies on health outcomes and the financial impact on the healthcare system. All studies reported that detection and management of HeFH in paediatric populations was cost-effective, regardless of the age of the children. However, cost-effectiveness varied depending on the method of case ascertainment - targeted screening was generally cheaper overall, but less effective, than whole-of-population screening, although both methods were generally cost-effective. SUMMARY: Detection and management of HeFH in paediatric populations is a cost-effective way to significantly lower the burden of disease later in life for these individuals. These strategies should be implemented across healthcare systems.

Societal health and economic burden of cardiovascular diseases in the population with type 2 diabetes in Qatar. A 10-year forecasting model.

AIMS: To predict the future health and economic burden of cardiovascular disease (CVD) in type 2 diabetes (T2D) in Qatar. MATERIALS AND METHODS: A dynamic multistate model was designed to simulate the progression of fatal and non-fatal CVD events among people with T2D in Qatar aged 40-79 years. First CVD events [i.e. myocardial infarction (MI) and stroke] were calculated via the 2013 Pooled Cohort Equation, while recurrent CVD events were sourced from the REACH registry. Key model outcomes were fatal and non-fatal MI and stroke, years of life lived, quality-adjusted life years, total direct medical costs and total productivity loss costs. Utility and cost model inputs were drawn from published sources. The model adopted a Qatari societal perspective. Sensitivity analyses were performed to test the robustness of estimates. RESULTS: Over 10 years among people with T2D, model estimates 108 195 [95% uncertainty interval (UI) 104 249-112 172] non-fatal MIs, 62 366 (95% UI 60 283-65 520) non-fatal strokes and 14 612 (95% UI 14 472-14 744) CVD deaths. The T2D population accrued 4 786 605 (95% UI 4 743 454, 4 858 705) total years of life lived and 3 781 833 (95% UI 3 724 718-3 830 669) total quality-adjusted life years. Direct costs accounted for 57.85% of the total costs, with a projection of QAR41.60 billion (US$11.40 billion) [95% UI 7.53-147.40 billion (US$2.06-40.38 billion)], while the total indirect costs were expected to exceed QAR30.31 billion (US$8.30 billion) [95% UI 1.07-162.60 billion (US$292.05 million-44.55 billion)]. CONCLUSIONS: The findings suggest a significant economic and health burden of CVD among people with T2D in Qatar and highlight the need for more enhanced preventive strategies targeting this population group.

Enhancing the Detection and Care of Heterozygous Familial Hypercholesterolemia in Primary Care: Cost-Effectiveness and Return on Investment.

BACKGROUND: Heterozygous familial hypercholesterolemia (HeFH) is under-detected and undertreated. A general practitioner-led screening and care program for HeFH effectively identified and managed patients with HeFH. We evaluated the cost-effectiveness and the return on investment of an enhanced-care strategy for HeFH in primary care in Australia. METHODS: We developed a multistate Markov model to estimate the outcomes and costs of a general practitioner-led detection and management strategy for HeFH in primary care compared with the standard of care in Australia. The population comprised individuals aged 50 to 80 years, of which 44% had prior cardiovascular disease. Cardiovascular risk, HeFH prevalence, treatment effects, and acute and chronic health care costs were derived from published sources. The study involved screening for HeFH using a validated data-extraction tool (TARB-Ex), followed by a consultation to improve care. The detection rate of HeFH was 16%, and 74% of the patients achieved target LDL-C (low-density lipoprotein cholesterol). Quality-adjusted life years, health care costs, productivity losses, incremental cost-effectiveness ratio, and return on investment ratio were evaluated, outcomes discounted by 5% annually, adopting a health care and a societal perspective. RESULTS: Over the lifetime horizon, the model estimated a gain of 870 years of life lived and 1033 quality-adjusted life years when the general practitioner-led program was employed compared with standard of care. This resulted in an incremental cost-effectiveness ratio of AU$14 664/quality-adjusted life year gained from a health care perspective. From a societal perspective, this strategy, compared with standard of care was cost-saving, with a return on investment of AU$5.64 per dollar invested. CONCLUSIONS: An enhanced general practitioner-led model of care for HeFH is likely to be cost-effective.

Systematic Review of Cost-Effectiveness Analysis for Surgical and Neurostimulation Treatments for Drug-Resistant Epilepsy in Adults.

BACKGROUND AND OBJECTIVES: Surgical and neurostimulator treatments are effective for reducing seizure burden in selected individuals living with drug-resistant epilepsy (DRE). We aimed to determine the presence and key model determinants for cost-effectiveness of these interventions, compared with medical management alone, to assist with decisions about resource allocation. METHODS: A systematic literature search was conducted on June 1, 2022, using MEDLINE, EMBASE, the NHS Economic Evaluation Database, and the Cost-Effectiveness Analysis database. Included studies were economic evaluations in adult DRE cohorts, comparing surgical and neurostimulator treatments (vagus nerve stimulation [VNS], responsive neurostimulation [RNS], and deep brain stimulation [DBS]) vs medical management alone and reporting cost-benefit analysis, cost-utility, or cost-effectiveness. Exclusion criteria were studies with pediatric cohorts and those published in a language other than English. Three independent reviewers screened, extracted, and assessed data against the Consolidated Health Economic Evaluation Reporting Standards checklist, and a fourth reviewer adjudicated discrepancies. RESULTS: Ten studies met inclusion criteria. Seven studies evaluated epilepsy surgery, and 3 evaluated neurostimulation treatments. All relevant studies established that epilepsy surgery is a cost-effective intervention compared with medical management alone, for quality-adjusted life-years and seizure freedom at 2 and 5 years. All relevant studies found neurostimulator treatments to be potentially cost-effective. The incremental cost-effectiveness ratio (ICER), with lower ICER indicating greater cost-effectiveness, was reported for 9 studies and varied between GBP £3,013 and US $61,333. Cost adaptation revealed ICERs from US $170 to US $121,726. Key model determinants included, but were not limited to, improved surgical outcomes and quality of life, reduced surgical and presurgical evaluation costs, higher rates of surgical eligibility after referral and evaluation, epilepsy subtype, less expensive neurostimulator devices with improved longevity, and cost analysis strategy used in the analysis. DISCUSSION: There is consistent evidence that epilepsy surgery is a cost-effective treatment of eligible candidates with DRE. Limited evidence suggests that VNS, RNS, and DBS may be cost-effective therapies for DRE, although more health economic evaluations alongside prospective clinical trials are needed to validate these findings. STUDY REGISTRATION INFORMATION: PROSPERO CRD42021278436.

Long-term cost-effectiveness of implementing a lifestyle intervention during pregnancy to reduce the incidence of gestational diabetes and type 2 diabetes.

AIMS/HYPOTHESIS: The aim of this study was to determine the long-term cost-effectiveness and return on investment of implementing a structured lifestyle intervention to reduce excessive gestational weight gain and associated incidence of gestational diabetes mellitus (GDM) and type 2 diabetes mellitus. METHODS: A decision-analytic Markov model was used to compare the health and cost-effectiveness outcomes for (1) a structured lifestyle intervention during pregnancy to prevent GDM and subsequent type 2 diabetes; and (2) current usual antenatal care. Life table modelling was used to capture type 2 diabetes morbidity, mortality and quality-adjusted life years over a lifetime horizon for all women giving birth in Australia. Costs incorporated both healthcare and societal perspectives. The intervention effect was derived from published meta-analyses. Deterministic and probabilistic sensitivity analyses were used to capture the impact of uncertainty in the model. RESULTS: The model projected a 10% reduction in the number of women subsequently diagnosed with type 2 diabetes through implementation of the lifestyle intervention compared with current usual care. The total net incremental cost of intervention was approximately AU$70 million, and the cost savings from the reduction in costs of antenatal care for GDM, birth complications and type 2 diabetes management were approximately AU$85 million. The intervention was dominant (cost-saving) compared with usual care from a healthcare perspective, and returned AU$1.22 (95% CI 0.53, 2.13) per dollar invested. The results were robust to sensitivity analysis, and remained cost-saving or highly cost-effective in each of the scenarios explored. CONCLUSIONS/INTERPRETATION: This study demonstrates significant cost savings from implementation of a structured lifestyle intervention during pregnancy, due to a reduction in adverse health outcomes for women during both the perinatal period and over their lifetime.

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% UI 1.90-30.45 billion) and AU$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.

Targeting Diabetes Prevention to More Disadvantaged Groups Improves Cost-Effectiveness: Implications of Inequality in Type 2 Diabetes From Theoretical Interventions.

OBJECTIVES: To determine the effect of socioeconomic status on efficacy and cost thresholds at which theoretical diabetes prevention policies become cost-effective. METHODS: We designed a life table model using real-world data that captured diabetes incidence and all-cause mortality in people with and without diabetes by socioeconomic disadvantage. The model used data from the Australian diabetes registry for people with diabetes and the Australian Institute of Health and Welfare for the general population. We simulated theoretical diabetes prevention policies and estimated the threshold at which they would be cost-effective and cost saving, overall, and by socioeconomic disadvantage, from the public healthcare perspective. RESULTS: From 2020 to 2029, 653 980 people were projected to develop type 2 diabetes, 101 583 in the least disadvantaged quintile and 166 744 in the most. Theoretical diabetes prevention policies that reduce diabetes incidence by 10% and 25% would be cost-effective in the total population at a maximum per person cost of Australian dollar (AU$) 74 (95% uncertainty interval: 53-99) and AU$187 (133-249) and cost saving at AU$26 (20-33) and AU$65 (50-84). Theoretical diabetes prevention policies remained cost-effective at a higher cost in the most versus least disadvantaged quintile (eg, a policy that reduces type 2 diabetes incidence by 25% would be cost-effective at AU$238 [169-319] per person in the most disadvantaged quintile vs AU$144 [103-192] in the least). CONCLUSIONS: Policies targeted at more disadvantaged populations will likely be cost-effective at higher costs and lower efficacy compared to untargeted policies. Future health economic models should incorporate measures of socioeconomic disadvantage to improve targeting of interventions.

Projecting the incidence and costs of major cardiovascular and kidney complications of type 2 diabetes with widespread SGLT2i and GLP-1 RA use: a cost-effectiveness analysis.

AIMS/HYPOTHESIS: Whether sodium-glucose co-transporter 2 inhibitors (SGLT2is) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are cost-effective based solely on their cardiovascular and kidney benefits is unknown. We projected the health and economic outcomes due to myocardial infarction (MI), stroke, heart failure (HF) and end-stage kidney disease (ESKD) among people with type 2 diabetes, with and without CVD, under scenarios of widespread use of these drugs. METHODS: We designed a microsimulation model using real-world data that captured CVD and ESKD morbidity and mortality from 2020 to 2040. The populations and transition probabilities were derived by linking the Australian Diabetes Registry (1.1 million people with type 2 diabetes) to hospital admissions databases, the National Death Index and the ESKD Registry using data from 2010 to 2019. We modelled four interventions: increase in use of SGLT2is or GLP-1 RAs to 75% of the total population with type 2 diabetes, and increase in use of SGLT2is or GLP-1 RAs to 75% of the secondary prevention population (i.e. people with type 2 diabetes and prior CVD). All interventions were compared with current use of SGLT2is (20% of the total population) and GLP-1 RAs (5% of the total population). Outcomes of interest included quality-adjusted life years (QALYs), total costs (from the Australian public healthcare perspective) and the incremental cost-effectiveness ratio (ICER). We applied 5% annual discounting for health economic outcomes. The willingness-to-pay threshold was set at AU$28,000 per QALY gained. RESULTS: The numbers of QALYs gained from 2020 to 2040 with increased SGLT2i and GLP-1 RA use in the total population (n=1.1 million in 2020; n=1.5 million in 2040) were 176,446 and 200,932, respectively, compared with current use. Net cost differences were AU$4.2 billion for SGLT2is and AU$20.2 billion for GLP-1 RAs, and the ICERs were AU$23,717 and AU$100,705 per QALY gained, respectively. In the secondary prevention population, the ICERs were AU$8878 for SGLT2is and AU$79,742 for GLP-1 RAs. CONCLUSIONS/INTERPRETATION: At current prices, use of SGLT2is, but not GLP-1 RAs, would be cost-effective when considering only their cardiovascular and kidney disease benefits for people with type 2 diabetes.

Economic Evaluation of the Community Benefit of the Australian Pregnancy Register of Antiseizure Medications.

BACKGROUND AND OBJECTIVE: The Raoul Wallenberg Australian Pregnancy Register (APR) was established to collect, analyze, and publish data on the risks to babies exposed to antiseizure medications (ASMs) and to facilitate quality improvements in management care over time. It is one of the seveal prospective observational pregnancy registers of ASMs that has been established around the world. Although the APR and other registries have contributed to knowledge gain that has been applied to decrease adverse pregnancy outcomes, their cost-effectiveness remains unknown. Here, we aimed to evaluate the economic impacts of the APR from both societal and health care system perspectives. METHODS: Using decision analytic modeling, we estimated the effectiveness (prevention of adverse pregnancy outcomes) and costs (costs of adverse pregnancy outcomes and the register itself) of the APR over a 20-year time horizon (2000-2019). The comparator was set as the adverse pregnancy outcomes collected by the APR between 1998 and 2002 (i.e., no APR derived improvements in care). In the scenario analysis, we conservatively assumed a 2.5% and 5% contribution of the APR to the savings in health care and societal costs. Adverse pregnancy outcomes included stillbirth, birth defects, and induced abortion. All cost data were derived from published sources. Health and economic outcomes were extrapolated to the total target Australian epilepsy population. The primary outcomes of interest were the return of investment (ROI) for the APR and incremental cost-effectiveness ratio (ICER) for cost per adverse outcome avoided. RESULTS: Over the 20-year time horizon, the ROI from the APR from a societal perspective was Australian dollars (AUD) 2,250 (i.e., every dollar spent on the program resulted in a return of AUD2,250). Over this time, it was estimated that 9,609 adverse pregnancy outcomes were avoided, and health care and societal costs were reduced by AUD 191 million and AUD 9.0 billion, respectively. Hence, from a health economic point of view, the APR was dominant, providing cost saving ICERs from both perspectives. DISCUSSION: Following its inception 20+ years ago, the APR has represented excellent value for investment for Australia, being also health-saving and cost saving from a societal and a health care perspective. With the growing number of marketed ASMs, the APR is expected to continue to have a major impact in the foreseeable future.

Lost Therapeutic Benefit of Delayed Low-Density Lipoprotein Cholesterol Control in Statin-Treated Patients and Cost-Effectiveness Analysis of Lipid-Lowering Intensification.

OBJECTIVES: Attainment of low-density lipoprotein cholesterol (LDL-C) therapeutic goals in statin-treated patients remains suboptimal. We quantified the health economic impact of delayed lipid-lowering intensification from an Australian healthcare and societal perspective. METHODS: A lifetime Markov cohort model (n = 1000) estimating the impact on coronary heart disease (CHD) of intensifying lipid-lowering treatment in statin-treated patients with uncontrolled LDL-C, at moderate to high risk of CHD with no delay or after a 5-year delay, compared with standard of care (no intensification), starting at age 40 years. Intensification was tested with high-intensity statins or statins + ezetimibe. LDL-C levels were extracted from a primary care cohort. CHD risk was estimated using the pooled cohort equation. The effect of cumulative exposure to LDL-C on CHD risk was derived from Mendelian randomization data. Outcomes included CHD events, quality-adjusted life-years (QALYs), healthcare and productivity costs, and incremental cost-effectiveness ratios (ICERs). All outcomes were discounted annually by 5%. RESULTS: Over the lifetime horizon, compared with standard of care, achieving LDL-C control with no delay with high-intensity statins prevented 29 CHD events and yielded 30 extra QALYs (ICERs AU$13 205/QALY) versus 22 CHD events and 16 QALYs (ICER AU$20 270/QALY) with a 5-year delay. For statins + ezetimibe, no delay prevented 53 CHD events and gave 45 extra QALYs (ICER AU$37 271/QALY) versus 40 CHD events and 29 QALYs (ICER of AU$44 218/QALY) after a 5-year delay. CONCLUSIONS: Delaying attainment of LDL-C goals translates into lost therapeutic benefit and a waste of resources. Urgent policies are needed to improve LDL-C goal attainment in statin-treated patients.

The Hospitalizations for Cardiovascular and Respiratory Conditions, Emergency Department Presentations and Economic Burden of Bushfires in Australia Between 2021 and 2030: A Modelling Study.

The health and environmental impacts of bushfires results in substantial economic costs to society. The present analysis sought to estimate the burden of bushfires in Australia over 10 years from 2021 to 2030 inclusive. A dynamic model with yearly cycles was constructed to simulate follow-up of the entire Australian population from 2021 to 2030, capturing deaths and years of life lived. Estimated numbers of bushfire-related-deaths, costs of related-hospitalizations, and broader economic costs were derived from published sources. A 5% annual discount rate was applied to all costs incurred and life years lived from 2022 onwards. Over the 10 years from 2021 to 2030, the modelled analysis predicted that 2418 [95% confidence interval (CI) 2412 - 2422] lives would be lost to bushfires, as well as 8590 [95% CI 8573 - 8606] years of life lost (discounted). Healthcare costs arising from deaths for smoke-related conditions, hospitalizations amounted to AUD $110 million [95% CI 91-129 million] (discounted). The impact on gross domestic product (GDP) totaled AUD $17.2 billion. A hypothetical intervention that reduces the impact of bushfires by 10% would save $11 million in healthcare costs and $1.9 billion in GDP. The health and economic burden of bushfires in Australia looms large during 2021 and 2030. This underscores the importance of actions to mitigate bushfire risk. The findings are useful for the future design and delivery and help policy makers to make informed decisions about investment in strategies to reduce the incidence and severity of future bushfires.

A Systematic Review of Cost-Effectiveness of Non-Statin Lipid-Lowering Drugs for Primary and Secondary Prevention of Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus.

Although studies of nonstatin lipid-lowering therapies have demonstrated cardiovascular benefits; whether these benefits provide good value has not been evaluated in type 2 diabetes mellitus patients. A systematic review was performed to include studies on the cost-effectiveness of non-statin lipid-lowering therapies in type 2 diabetes mellitus patients with/without cardiovascular disease. Thirteen studies were included; ezetimibe (n = 8), proprotein convertase subtilisin/kexin type 9 inhibitors (n = 4), fenofibrate (n = 2), nicotinic acid (n = 1), extended-release niacin/laropiprant (n = 1), and icosapent ethyl (n = 1). Six studies considered ezetimibe + statin to be a cost-effective compared to statins monotherapy, three studies suggested that proprotein convertase subtilisin/kexin type 9inhibitors + statins were not cost-effective compared to statin + ezetimibe. Fenofibrate was a cost-effective either as monotherapy or combined with a statin compared to statin or fenofibrate monotherapy. Nicotinic acid and proprotein convertase subtilisin/kexin type 9 compared to statin monotherapy were also cost-effective. Icosapent ethyl was cost-effective compared to standard care but not using the wholesale acquisition cost.

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%. Interventions for identified high-risk variant carriers follow current Australian guidelines, modelling imperfect uptake and adherence. Outcome measures were morbidity and mortality due to cancer (breast, ovarian, colorectal and endometrial) and coronary heart disease (CHD) over a lifetime horizon, from healthcare-system and societal perspectives. Outcomes included quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER), discounted 5% annually (with 3% discounting in scenario analysis). 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% of the population. Our findings suggest that this intervention would be cost-effective from a healthcare-system perspective, yielding an ICER of AU$23,926 (∼£12,050/€14,110/US$15,345) per QALY gained over the status quo. In scenario analysis with 3% discounting, an ICER of AU$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).

Projected New-Onset Cardiovascular Disease by Socioeconomic Group in Australia.

BACKGROUND: Socioeconomic status has an important effect on cardiovascular disease (CVD). Data on the economic implications of CVD by socioeconomic status are needed to inform healthcare planning. OBJECTIVES: The aim of this study was to project new-onset CVD and related health economic outcomes in Australia by socioeconomic status from 2021 to 2030. METHODS: A dynamic population model was built to project annual new-onset CVD by socioeconomic quintile in Australians aged 40-79 years from 2021 to 2030. Cardiovascular risk was estimated using the Pooled Cohort Equation (PCE) from Australian-specific data, stratified for each socioeconomic quintile. The model projected years of life lived, quality- adjusted life-years (QALYs), acute healthcare medical costs, and productivity losses due to new-onset CVD. All outcomes were discounted by 5% annually. RESULTS: PCE estimates showed that 8.4% of people in the most disadvantaged quintile were at high risk of CVD, compared with 3.7% in the least disadvantaged quintile (p < 0.001). From 2021 to 2030, the model projected 32% more cardiovascular events in the most disadvantaged quintile compared with the least disadvantaged (127,070 in SE 1 vs. 96,222 in SE 5). Acute healthcare costs in the most disadvantaged quintile were Australian dollars (AU$) 183 million higher than the least disadvantaged, and the difference in productivity costs was AU$959 million. Removing the equity gap (by applying the cardiovascular risk from the least disadvantaged quintile to the whole population) would prevent 114,822 cardiovascular events and save AU$704 million of healthcare costs and AU$3844 million of lost earnings over the next 10 years. CONCLUSION: Our results highlight the pressing need to implement primary prevention interventions to reduce cardiovascular health inequity. This model provides a platform to incorporate socioeconomic status into health economic models by estimating which interventions are likely to yield more benefits in each socioeconomic quintile.

Population genomic screening of young adults for familial hypercholesterolaemia: a cost-effectiveness analysis.

AIMS: The aim of this study was to assess the impact and cost-effectiveness of offering population genomic screening to all young adults in Australia to detect heterozygous familial hypercholesterolaemia (FH). METHODS AND RESULTS: We designed a decision analytic Markov model to compare the current standard of care for heterozygous FH diagnosis in Australia (opportunistic cholesterol screening and genetic cascade testing) with the alternate strategy of population genomic screening of adults aged 18-40 years to detect pathogenic variants in the LDLR/APOB/PCSK9 genes. We used a validated cost-adaptation method to adapt findings to eight high-income countries. The model captured coronary heart disease (CHD) morbidity/mortality over a lifetime horizon, from healthcare and societal perspectives. Risk of CHD, treatment effects, prevalence, and healthcare costs were estimated from published studies. Outcomes included quality-adjusted life years (QALYs), costs and incremental cost-effectiveness ratio (ICER), discounted 5% annually. Sensitivity analyses were undertaken to explore the impact of key input parameters on the robustness of the model. Over the lifetime of the population (4 167 768 men; 4 129 961 women), the model estimated a gain of 33 488years of life lived and 51 790 QALYs due to CHD prevention. Population genomic screening for FH would be cost-effective from a healthcare perspective if the per-test cost was ≤AU$250, yielding an ICER of

Future burden of cardiovascular disease in Australia: impact on health and economic outcomes between 2020 and 2029.

AIMS: To estimate the health and economic burden of new and established cardiovascular disease from 2020 to 2029 in Australia. METHODS AND RESULTS: A two-stage multistate dynamic model was developed to predict the burden of the incident and prevalent cardiovascular disease, for Australians 40-90 years old from 2020 to 2029. The model captured morbidity, mortality, years of life lived, quality-adjusted life years, healthcare costs, and productivity losses. Cardiovascular risk for the primary prevention population was derived using Australian demographic data and the Pooled Cohort Equation. Risk for the secondary prevention population was derived from the REACH registry. Input data for costs and utilities were extracted from published sources. All outcomes were annually discounted by 5%. A number of sensitivity analyses were undertaken to test the robustness of the study. Between 2020 and 2029, the model estimates 377 754 fatal and 991 375 non-fatal cardiovascular events. By 2029, 1 061 756 Australians will have prevalent cardiovascular disease (CVD). The population accrued 8 815 271 [95% uncertainty interval (UI) 8 805 083-8 841 432] years of life lived with CVD and 5 876 975 (5 551 484-6 226 045) QALYs. The total healthcare costs of CVD were projected to exceed Australian dollars (AUD) 61.89 (61.79-88.66) billion, and productivity losses will account for AUD 78.75 (49.40-295.25) billion, driving the total cost to surpass AUD 140.65 (123.13-370.23) billion. CONCLUSION: Cardiovascular disease in Australia has substantial impacts in terms of morbidity, mortality, and lost revenue to the healthcare system and the society. Our modelling provides important information for decision making in relation to the future burden of cardiovascular disease.

Cost-Effectiveness of Empagliflozin and Metformin Combination Versus Standard Care as First-Line Therapy in Patients With Type 2 Diabetes Mellitus.

OBJECTIVE: Sodium-glucose cotransporter 2 inhibitors have been shown to reduce cardiovascular events but are currently not used as the first-line therapy. This study was conducted to evaluate the cost-effectiveness of first-line empagliflozin plus metformin versus metformin monotherapy among Australians with type 2 diabetes mellitus (T2DM) and existing cardiovascular disease (CVD). METHODS: A Markov model with 1-year cycles and a 5-year time horizon was constructed to simulate the occurrence of recurrent cardiovascular events among Australians aged 50 to 84 years with T2DM and CVD. Efficacy results were derived from the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose trial. Costs and utilities were drawn from published sources. The evaluation adopted both health care and societal perspectives, with the latter ascribing the Australian government's "value of statistical life year" (A$213 000) to each year lived by a person. Future outcomes were discounted at 5% annually. Sensitivity analyses were conducted to enhance the robustness of conclusions. RESULTS: Compared with metformin monotherapy, first-line empagliflozin plus metformin reduced overall cardiovascular events by 0.82% and overall deaths by 7.72% over 5 years. There were 0.2 years of life saved per person and 0.16 quality-adjusted life years gained, at a net health care cost of A$4408. These equated to incremental cost-effectiveness ratios of A$22 076 per year of life saved and A$28 244 per quality-adjusted life year gained. The gains in the value of statistical life year equated to A$42 530 per person, meaning that from a societal perspective, the intervention was cost-saving. CONCLUSION: First-line empagliflozin plus metformin may represent a cost-effective strategy for the management of T2DM and CVD in Australia.