Health economic analysis of polygenic risk score use in primary prevention of coronary artery disease - A system dynamics model.

Background: Primary prevention programs utilising traditional risk scores fail to identify all individuals who suffer acute cardiovascular events. We aimed to model the impact and cost effectiveness of incorporating a Polygenic risk scores (PRS) into the cardiovascular disease CVD primary prevention program in Australia, using a whole-of-system model. Methods: System dynamics models, encompassing acute and chronic CVD care in the Australian healthcare setting, assessing the cost-effectiveness of incorporating a CAD-PRS in the primary prevention setting. The time horizon was 10-years. Results: Pragmatically incorporating a CAD-PRS in the Australian primary prevention setting in middle-aged individuals already attending a Heart Health Check (HHC) who are determined to be at low or moderate risk based on the 5-year Framingham risk score (FRS), with conservative assumptions regarding uptake of PRS, could have prevented 2, 052 deaths over 10-years, and resulted in 24, 085 QALYs gained at a cost of $19, 945 per QALY with a net benefit of $724 million. If all Australians overs the age of 35 years old had their FRS and PRS performed, and acted upon, 12, 374 deaths and 60, 284 acute coronary events would be prevented, with 183, 682 QALYs gained at a cost of $18, 531 per QALY, with a net benefit of $5, 780 million. Conclusions: Incorporating a CAD-PRS in a contemporary primary prevention setting in Australia would result in substantial health and societal benefits and is cost-effective. The broader the uptake of CAD-PRS in the primary prevention setting in middle-aged Australians, the greater the impact and the more cost-effective the strategy.

The economic costs and cost-effectiveness of HIV self-testing among truck drivers in Kenya.

HIV status awareness is critical for ending the HIV epidemic but remains low in high-HIV-risk and hard-to-reach sub-populations. Targeted, efficient interventions are needed to improve HIV test-uptake. We examined the incremental cost-effectiveness of offering the choice of self-administered oral HIV-testing (HIVST-Choice) compared with provider-administered testing only [standard-of-care (SOC)] among long-distance truck drivers. Effectiveness data came from a randomized-controlled trial conducted at two roadside wellness clinics in Kenya (HIVST-Choice arm, n = 150; SOC arm, n = 155). Economic cost data came from the literature, reflected a societal perspective and were reported in 2020 international dollars (I$), a hypothetical currency with equivalent purchasing power as the US dollar. Generalized Poisson and linear gamma regression models were used to estimate effectiveness and incremental costs, respectively; incremental effectiveness was reported as the number of long-distance truck drivers needing to receive HIVST-Choice for an additional HIV test-uptake. We calculated the incremental cost-effectiveness ratio (ICER) of HIVST-Choice compared with SOC and estimated 95% confidence intervals (CIs) using non-parametric bootstrapping. Uncertainty was assessed using deterministic sensitivity analysis and the cost-effectiveness acceptability curve. HIV test-uptake was 23% more likely for HIVST-Choice, with six individuals needing to be offered HIVST-Choice for an additional HIV test-uptake. The mean per-patient cost was nearly 4-fold higher in HIVST-Choice (I$39.28) versus SOC (I$10.80), with an ICER of I$174.51, 95% CI [165.72, 194.59] for each additional test-uptake. HIV self-test kit and cell phone service costs were the main drivers of the ICER, although findings were robust even at highest possible costs. The probability of cost-effectiveness approached 1 at a willingness-to-pay of I$200 for each additional HIV test-uptake. HIVST-Choice improves HIV-test-uptake among truck drivers at low willingness-to-pay thresholds, suggesting that HIV self-testing is an efficient use of resources. Policies supporting HIV self-testing in similar high risk, hard-to-reach sub-populations may expedite achievement of international targets.

Cost-effectiveness analysis of implementing polygenic risk score in a workplace cardiovascular disease prevention program.

Background: Polygenic risk score for coronary artery disease (CAD-PRS) improves precision in assessing the risk of cardiovascular diseases and is cost-effective in preventing cardiovascular diseases in a health system and may be cost-effective in other settings and prevention programs such as workplace cardiovascular prevention programs. Workplaces provide a conducitve environment for cardiovascular prevention interventions, but the cost-effectiveness of CAD-PRS in a workplace setting remains unknown. This study examined the cost-effectiveness of integrating CAD-PRS in a workplace cardiovascular disease prevention program compared to the standard cardiovascular workplace program without CAD-PRS and no-workplace prevention program. Methods: We developed a cohort simulation model to project health benefits (quality-adjusted life years gained) and costs over a period of 5 years in a cohort of employees with a mean age of 50 years. The model health states reflected the risk of disease (coronary artery disease and ischemic stroke) and statin prevention therapy side effects (diabetes, hemorrhagic stroke, and myopathy). We considered medical and lost productivity costs. Data were obtained from the literature, and the analysis was performed from a self-insured employer perspective with future costs and quality-adjusted life years discounted at 3% annually. Uncertainty in model parameter inputs was assessed using deterministic and probabilistic sensitivity analyses. Three programs were compared: (1) a workplace cardiovascular program that integrated CAD-PRS with the pooled cohort equation-a standard of care for assessing the risk of cardiovascular diseases (CardioriskSCORE); (2) a workplace cardiovascular prevention program without CAD-PRS (Standard-WHP); and (3) no-workplace health program (No-WHP). The main outcomes were total costs (US $2019), incremental costs, incremental quality-adjusted life years, and incremental cost-effectiveness ratio. Results: CardioriskSCORE lowered employer costs ($53 and $575) and improved employee quality-adjusted life years (0.001 and 0.005) per employee screened compared to Standard-WHP and No-WHP, respectively. The effectiveness of statin prevention therapy, employees' baseline cardiovascular risk, the proportion of employees that enrolled in the program, and statin adherence had the largest effect size on the incremental net monetary benefit. However, despite the variation in parameter input values, base case results remained robust. Conclusion: Polygenic testing in a workplace cardiovascular prevention program improves employees' quality of life and simultaneously lowers health costs and productivity monetary loss for employers.

Integrating a Polygenic Risk Score for Coronary Artery Disease as a Risk-Enhancing Factor in the Pooled Cohort Equation: A Cost-Effectiveness Analysis Study.

Background Cardiovascular diseases are the leading cause of death in the United States, yet a significant proportion of adults at high risk remain undetected by standard screening practices. Polygenic risk score for coronary artery disease (CAD-PRS) improves precision in determining the 10-year risk of atherosclerotic cardiovascular disease but health benefits and health care costs associated with CAD-PRS are unknown. We examined the cost-effectiveness of including CAD-PRS as a risk-enhancing factor in the pooled cohort equation (PCE)-the standard of care for determining the risk of atherosclerotic cardiovascular disease-versus PCE alone. Methods and Results We applied a Markov model on a cohort of 40-year-old individuals with borderline or intermediate 10-year risk (5% to <20%) for atherosclerotic cardiovascular disease to identify those in the top quintile of the CAD-PRS distribution who are at high risk and eligible for statin prevention therapy. Health outcomes examined included coronary artery disease (CAD; ie, myocardial infarction) and ischemic stroke. The model projected medical costs (2019 US$) of screening for CAD, statin prevention therapy, treatment, and monitoring patients living with CAD or ischemic stroke and quality-adjusted life-years for PCE+CAD-PRS versus PCE alone. Deterministic and probabilistic sensitivity analyses and scenario analyses were performed to examine uncertainty in parameter inputs. PCE+CAD-PRS was dominant compared with PCE alone in the 5- and 10-year time horizons. We found that, respectively, PCE+CAD-PRS had 0.003 and 0.011 higher mean quality-adjusted life-years and $40 and $181 lower mean costs per person screened, with 29 and 50 fewer events of CAD and ischemic stroke in a cohort of 10 000 individuals compared with PCE alone. The risk of developing CAD, the effectiveness of statin prevention therapy, and the cost of treating CAD had the largest impact on the cost per quality-adjusted life-year gained. However, this cost remained below the $50 000 willingness-to-pay threshold except when the annual risk of developing CAD was <0.006 in the 5-year time horizon. Results from Monte Carlo simulation indicated that PCE+CAD-PRS would be cost-effective. with the probability of 94% and 99% at $50 000 willingness-to-pay threshold in the 5- and 10-year time horizon, respectively. Conclusions Implementing CAD-PRS as a risk-enhancing factor in the PCE to determine the risk of atherosclerotic cardiovascular disease reduced the mean cost per individual, improved quality-adjusted life-years, and averted future events of CAD and ischemic stroke when compared with PCE alone.

Mathematical modelling to inform 'treat all' implementation in sub-Saharan Africa: a scoping review.

OBJECTIVE: Despite widespread uptake, only half of sub-Saharan African countries have fully implemented the World Health Organization's 'treat all' policy, hindering achievement of global HIV targets. We examined literature on mathematical modelling studies that sought to inform scale-up and implementation of 'treat all' in sub-Saharan Africa. METHODS: We conducted a scoping review, a research synthesis to assess emerging evidence and identify gaps, of peer-reviewed literature, extracting study characteristics on 'treat all' policies and assumptions, setting, key populations, outcomes and findings. Studies were narratively summarised and potential gaps characterised. RESULTS: We identified 16 studies examining 'treat all' alone (n=12) or with expanded testing (n=7) and/or care continuum improvements (n=6). Twelve studies examined 'treat all' for Southern African countries, while none did so for Central Africa. Four included the role of resistance; one evaluated any key population. A range of health and economic outcomes were reported, although fewer studies formally assessed budget impact. Fourteen studies involved co-authors with any in-country affiliation; one study also had co-authors with local government affiliation. Overall, 'treat all' improves health outcomes and is cost-effective compared to deferred HIV treatment; 'treat all' with expanded testing or care continuum improvements may provide further health benefits. However, studies generally used optimistic assumptions about the implementation of expanded testing or care continuum improvements. CONCLUSIONS: The modelling literature demonstrates improved health and economic benefits of 'treat all'. Using mathematical modelling to inform real-world implementation of 'treat all' requires realistic assumptions about expanded testing and care continuum interventions across a wide range of settings and populations.