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      Integrating the Biology of Cardiovascular Disease into the Epidemiology of Economic Decision Modelling via Mendelian Randomisation

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          Abstract

          Health economic analyses are essential for health services research, providing decision-makers and payers with evidence about the value of interventions relative to their opportunity cost. However, many health economic approaches are still limited, especially regarding the primary prevention of cardiovascular disease (CVD). In this article, we discuss some limitations to current health economic models and then outline an approach to address these via the incorporation of genomics into the design of health economic models for CVD. We propose that when a randomised clinical trial is not possible or practical, health economic models for primary prevention of CVD can be based on Mendelian randomisation analyses, a technique to assess causality in observational data. We discuss the advantages of this approach, such as integrating well-known disease biology into health economic models and how this may overcome current statistical approaches to assessing the benefits of interventions. We argue that this approach may provide the economic argument for integrating genomics into clinical practice and the efficient targeting of newer therapeutics, transforming our approach to the primary prevention of CVD, thereby moving from reactive to preventive healthcare. We end by discussing some limitations and potential pitfalls of this approach.

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          Most cited references42

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          UK Biobank: An Open Access Resource for Identifying the Causes of a Wide Range of Complex Diseases of Middle and Old Age

          Cathie Sudlow and colleagues describe the UK Biobank, a large population-based prospective study, established to allow investigation of the genetic and non-genetic determinants of the diseases of middle and old age.
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            General cardiovascular risk profile for use in primary care: the Framingham Heart Study.

            Separate multivariable risk algorithms are commonly used to assess risk of specific atherosclerotic cardiovascular disease (CVD) events, ie, coronary heart disease, cerebrovascular disease, peripheral vascular disease, and heart failure. The present report presents a single multivariable risk function that predicts risk of developing all CVD and of its constituents. We used Cox proportional-hazards regression to evaluate the risk of developing a first CVD event in 8491 Framingham study participants (mean age, 49 years; 4522 women) who attended a routine examination between 30 and 74 years of age and were free of CVD. Sex-specific multivariable risk functions ("general CVD" algorithms) were derived that incorporated age, total and high-density lipoprotein cholesterol, systolic blood pressure, treatment for hypertension, smoking, and diabetes status. We assessed the performance of the general CVD algorithms for predicting individual CVD events (coronary heart disease, stroke, peripheral artery disease, or heart failure). Over 12 years of follow-up, 1174 participants (456 women) developed a first CVD event. All traditional risk factors evaluated predicted CVD risk (multivariable-adjusted P<0.0001). The general CVD algorithm demonstrated good discrimination (C statistic, 0.763 [men] and 0.793 [women]) and calibration. Simple adjustments to the general CVD risk algorithms allowed estimation of the risks of each CVD component. Two simple risk scores are presented, 1 based on all traditional risk factors and the other based on non-laboratory-based predictors. A sex-specific multivariable risk factor algorithm can be conveniently used to assess general CVD risk and risk of individual CVD events (coronary, cerebrovascular, and peripheral arterial disease and heart failure). The estimated absolute CVD event rates can be used to quantify risk and to guide preventive care.
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              Comparison of Sociodemographic and Health-Related Characteristics of UK Biobank Participants With Those of the General Population

              Abstract The UK Biobank cohort is a population-based cohort of 500,000 participants recruited in the United Kingdom (UK) between 2006 and 2010. Approximately 9.2 million individuals aged 40–69 years who lived within 25 miles (40 km) of one of 22 assessment centers in England, Wales, and Scotland were invited to enter the cohort, and 5.5% participated in the baseline assessment. The representativeness of the UK Biobank cohort was investigated by comparing demographic characteristics between nonresponders and responders. Sociodemographic, physical, lifestyle, and health-related characteristics of the cohort were compared with nationally representative data sources. UK Biobank participants were more likely to be older, to be female, and to live in less socioeconomically deprived areas than nonparticipants. Compared with the general population, participants were less likely to be obese, to smoke, and to drink alcohol on a daily basis and had fewer self-reported health conditions. At age 70–74 years, rates of all-cause mortality and total cancer incidence were 46.2% and 11.8% lower, respectively, in men and 55.5% and 18.1% lower, respectively, in women than in the general population of the same age. UK Biobank is not representative of the sampling population; there is evidence of a “healthy volunteer” selection bias. Nonetheless, valid assessment of exposure-disease relationships may be widely generalizable and does not require participants to be representative of the population at large.
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                Author and article information

                Contributors
                zanfina.ademi@monash.edu
                Journal
                Pharmacoeconomics
                Pharmacoeconomics
                Pharmacoeconomics
                Springer International Publishing (Cham )
                1170-7690
                1179-2027
                25 August 2022
                25 August 2022
                2022
                : 40
                : 11
                : 1033-1042
                Affiliations
                [1 ]GRID grid.1002.3, ISNI 0000 0004 1936 7857, Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, , Monash University, ; 381 Royal Parade, Parkville, Melbourne, 3052 Australia
                [2 ]GRID grid.1002.3, ISNI 0000 0004 1936 7857, School of Public Health and Preventive Medicine, , Monash University, ; Melbourne, Australia
                [3 ]GRID grid.1051.5, ISNI 0000 0000 9760 5620, Baker Heart and Diabetes Institute, ; Melbourne, Australia
                [4 ]GRID grid.1010.0, ISNI 0000 0004 1936 7304, Adelaide Medical School, , University of Adelaide, ; Adelaide, Australia
                [5 ]GRID grid.1002.3, ISNI 0000 0004 1936 7857, Victorian Heart Institute, , Monash University, ; Melbourne, Australia
                [6 ]GRID grid.5335.0, ISNI 0000000121885934, Centre for Naturally Randomised Trials, , University of Cambridge, ; Cambridge, UK
                Author information
                http://orcid.org/0000-0002-0625-3522
                Article
                1183
                10.1007/s40273-022-01183-1
                9550676
                36006601
                7be1416e-4fcb-44d8-92b3-e2db6f8d2ff4
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 10 August 2022
                Funding
                Funded by: National Health and Medical Research Council Ideas Grants
                Award ID: 2012582
                Award Recipient :
                Funded by: Monash University
                Categories
                Review Article
                Custom metadata
                © Springer Nature Switzerland AG 2022

                Economics of health & social care
                Economics of health & social care

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