An Economic Framework for Evaluating Biomarkers Used to Target CVD Prevention

描述(由申请人提供)：指南建议计算全球心血管(CVD)风险，以便将有效的预防干预措施，如阿司匹林和他汀类药物，定向到最有可能受益的人，并通过不治疗低风险者来限制不良反应和成本。通过使用新的生物标记物提高我们预测未来谁将遭受心血管疾病事件的能力，应该有助于我们改善预防干预的针对性，从而改善健康结果。近年来已经发现了许多这样的标记物，其中一些已经得到了广泛的研究；然而，人们普遍认为，知识中存在着一个“关键差距”，这阻碍了关于是否应该在临床实践中采用这些生物标记物的有效决策。我们认为，这一关键差距是缺乏关于生物标记物靶向战略的净健康和经济影响的证据的结果。为了解决这一差距，我们建议开发一个决策分析/成本效益建模框架，以评估任何可用于靶向使用阿司匹林和他汀类药物作为心血管疾病一级预防的生物标记物(目标1)。对于这项任务，我们将使用UNC/RTI CHD预防模型，这是一个已建立的模型，重点是阿司匹林和他汀类药物预防CHD和中风的成本效益。该模型将通过一系列系统评估进行更新，以纳入有关阿司匹林和他汀类药物有效性和副作用的最新数据，然后进行重组，以允许基于生物标记物测量的“测试-治疗”策略(需要对4种不同的“子场景”进行并行建模，以允许3种可能的测试-治疗阈值)，并促进测试-治疗策略与“全部治疗”和“无治疗”(不会招致成本和与测试本身相关的任何不良影响的策略)的比较。然后，该框架将用于评估冠状动脉钙化(目标2)。这种极具争议的生物标志物是冠心病风险的一个强有力的独立预测指标，但它的测量成本很高，并使患者暴露在电离辐射中。我们将根据年龄、性别、低密度脂蛋白水平和心血管疾病风险的不同，在一套全面的临床情景中对不同的冠状动脉钙治疗阈值进行系统评估，并在成本和健康影响以及增量成本效益方面进行比较。最后，我们将建立一个在线界面，允许用户通过输入生物标记物出版物中常见的信息来筛选用于靶向阿司匹林和他汀类药物治疗的任何生物标记物(在相对理想的情况下)，并允许用户改变关键参数，如他汀类药物的成本(目标3)。我们的项目将弥合关于心血管疾病生物标记物使用的知识的关键差距，产生可立即用于驱动理性决策的冠状动脉钙的关键证据，一个允许研究人员和政策制定者筛选其他生物标记物用于这一环境的在线工具，以及评估生物标记物靶向预防在其他环境中的使用的路线图。 与公共健康相关：“心脏扫描”冠状动脉钙和其他新发现的测试(“生物标志物”)可以帮助确定谁有心脏病发作和中风的风险，谁应该接受药物治疗，以降低他们的风险。通过估计在美国常规使用这些测试可以预防多少心脏病发作、中风和死亡，以及这将花费多少钱，我们的研究将帮助政策制定者决定医生何时应该下令进行心脏扫描或其他生物标志物测试。

DESCRIPTION (provided by applicant): Guidelines recommend calculation of global cardiovascular (CVD) risk in order to target effective prevention interventions such as aspirin and statins to those most likely to benefit and to limit adverse effects and costs by not treating those at low risk. Improving our ability to predict who will suffer future CVD events through use of novel biomarkers should help us improve targeting of preventive interventions and thereby improve health outcomes. Many such markers have been identified over recent years, and some have been studied extensively; however, a widely-acknowledged "critical gap" in knowledge exists that has hindered effective decision-making about whether such biomarkers should be adopted in clinical practice. It is our view that this critical gap is the result of a lack of evidence about the net health and economic impact of biomarker targeting strategies. To address this gap, we propose to develop a decision analysis/cost-effectiveness modeling framework for evaluating any biomarker that could be used to target use of aspirin and statins for primary prevention of CVD (Aim 1). For this task, we will use the UNC/RTI CHD Prevention Model, an established model focusing on the cost-effectiveness of aspirin and statin prescribing for prevention of CHD and stroke. The model will be updated via a series of systematic reviews to incorporate the latest data on effectiveness and adverse effects of aspirin and statins, and then restructured to allow "Test-and-Treat" strategies based on biomarker measurements (requiring parallel modeling of 4 different "sub-scenarios" to allow for 3 possible Test-and-Treat treatment thresholds), and to facilitate comparison of Test-and-Treat strategies with Treat All and Treat None (strategies not incurring the cost and any adverse effects associated with the test itself). This framework will then be used to evaluate coronary calcium (Aim 2). This extremely controversial biomarker is a strong independent predictor of CHD risk, but it is expensive to measure and exposes the patient to ionizing radiation. We will undertake a systematic evaluation of different coronary calcium treatment thresholds in a comprehensive set of clinical scenarios varied in terms of age, sex, LDL level and CVD risk, and compared in terms of cost and health impact, and incremental cost-effectiveness. Finally, we will build an online interface allowing users to screen ANY biomarker for use in targeting aspirin and statin therapy (in a relatively ideal scenario) by inputting information commonly available in biomarker publications, and allowing users to vary key parameters such as the cost of statins (Aim 3). Our project would close the critical gap in knowledge on CVD biomarker use, produce key evidence for coronary calcium that could be used immediately to drive rational policy-making, an online tool allowing researchers and policymakers to screen other biomarkers for use in this setting, and a roadmap for evaluating use of biomarker targeted prevention in other settings. PUBLIC HEALTH RELEVANCE: "Heart scans" for coronary calcium and other newly discovered tests ("biomarkers") can help identify persons at risk for heart attacks and stroke who should be treated with medications to lower their risk. By estimating how many heart attacks, strokes and deaths could be prevented by using these tests routinely in the U.S. and how much money this would cost, our study will help policymakers decide when doctors should order a heart scan or other biomarker test.