A Novel Approach to Examine Within-Class Therapeutic Exchangeability of Medications

一种检查药物类内治疗可互换性的新方法

基本信息

批准号：
10599249
负责人：
Tobias Gerhard
金额：
$ 58.06万
依托单位：
RUTGERS BIOMEDICAL AND HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10599249
关键词：
Affect Amputation Anticoagulants Area Atherosclerosis Atrial Fibrillation Atrial Flutter Brain hemorrhage Cardiovascular Diseases Cardiovascular system Cause of Death Cessation of life Characteristics Chronic Clinical Clinical Medicine Cost Savings Data Dipeptidyl Peptidases Disease Drug Insurance Drug Prescriptions Drug usage Economics Elderly Enrollment Ensure Event Face Formularies Future Glucose Head Healthcare Systems Heart failure Hydroxymethylglutaryl-CoA Reductase Inhibitors Individual Ischemic Stroke Knee Knowledge Light Manufacturer Marketing Measures Medical Records Medicare Medicare claim Meta-Analysis Methodology Methods Natural experiment Non-Insulin-Dependent Diabetes Mellitus Oral Outcome Outcome Measure Patient-Focused Outcomes Patients Pharmaceutical Preparations Population Privatization Process Public Health Randomized, Controlled Trials Research Research Design Risk Secondary Prevention Sodium Stroke prevention Structure Therapeutic Therapeutic Equivalency Uncertainty Update Validation Variant Withdrawal Work atorvastatin beneficiary clinical effect clinically relevant comparative comparative effectiveness study cost data resource design drug development economic implication economic incentive evidence base financial incentive high risk improved indexing inhibitor innovation novel novel strategies research and development rosuvastatin stroke risk symporter treatment guidelines

项目摘要

Despite almost complete absence of adequate data from head-to-head randomized controlled trials, treatment guidelines and prescription drug insurance formularies typically consider individual drugs within medication classes as equally effective and equally safe. Yet, incorrect assumptions regarding therapeutic exchangeability expose patients to suboptimal treatments and adverse clinical outcomes, particularly older adults, who are disproportionately affected by chronic conditions and are the largest per capita consumers of prescription medications. Despite its substantial clinical and economic implications, therapeutic exchangeability remains remarkably understudied and represents a problem without a feasible current solution. We thus propose a novel and feasible approach to evaluate the therapeutic exchangeability of same-class drugs. The proposed studies will take advantage of natural experiments created by the structure of the Medicare Part D drug benefit and the variable financial incentives that Part D plans receive from manufacturers. Due to plan- specific formulary management strategies, Part D enrollees initiating a new medication often face substantially different out-of-pocket costs for alternative drugs within the same class. The differences in out-of-pocket costs among alternative same-class drugs among the hundreds of Part D plans will serve as instrumental variables (IVs). Because these financial incentives strongly affect the choice of one drug of a class over another and are independent of the patients’ clinical characteristics (as demonstrated by strong preliminary data), they facilitate valid IV estimation. Outcome validation from primary medical records and cause of death data from the National Death Index further improve the rigor of the study. Using existing data on >22 million Medicare beneficiaries, the proposed study will examine 4 carefully selected drug classes to establish a new methodological framework for the systematic assessment of within-class therapeutic exchangeability from observational data: 1) direct oral anticoagulants (DOACs) for stroke prevention in atrial fibrillation or atrial flutter, 2) dipeptidyl peptidase 4-inhibitors (DPP-4s) for type 2 diabetes, 3) high potency statins for secondary prevention of atherosclerotic cardiovascular (CV) disease, and 4) sodium-glucose co-transporter-2 inhibitors (SGLT-2s) for type 2 diabetes. These were selected based on explicit criteria: high rates of use in Part D beneficiaries, uncertainty about therapeutic exchangeability within the class, sufficient variation in out-of-pocket costs among alternative agents, and ability to validly measure outcomes in Medicare claims. We included examples with strong priors against (DPP-4s and CV outcomes) and for (SGLT-2s and amputations) within-class differences to show we can reproduce expected findings, and others for which differences are uncertain (e.g., DOACs and ischemic stroke). This proposal begins a highly promising novel line of work to feasibly generate valid and critically needed evidence on therapeutic exchangeability within widely-used drug classes among older adults, serve as the basis for future confirmatory studies, and improve clinical medicine, patient outcomes, and public health.

尽管几乎完全缺乏来自头对头随机对照试验的足够数据，治疗指南和处方药保险处方集通常会考虑范围内的个别药物药物类别同样有效且同样安全然而，关于治疗的错误假设。可互换性使患者面临次优的治疗和不良的临床结果，尤其是老年患者成年人，他们受慢性病的影响尤为严重，并且是人均最大的消费者尽管处方药具有重大的临床和经济意义，但治疗的可互换性。仍然很少得到充分研究，并且代表了一个目前没有可行解决方案的问题。提出了一种新颖且可行的方法来评估同类药物的治疗可互换性。拟议的研究将利用 Medicare D 部分结构创建的自然实验 D 部分计划从制造商处获得的药品福利和可变的财务激励措施。特定的处方管理策略，D 部分的参与者开始使用新药物时经常面临很大的困难同一类别的替代药物的自付费用不同。数百种 D 部分计划中的替代同级药物将作为工具变量 (IV) 因为这些经济激励措施强烈影响一类药物相对于另一类药物的选择，并且是独立于患者的临床特征（如强有力的初步数据所证明），它们有助于根据主要医疗记录和死亡原因数据进行有效的 IV 估计。国家死亡指数进一步提高了研究的严谨性，拟议的研究将利用超过 2200 万医疗保险受益人的现有数据来检查 4 种精心挑选的药物类别，以建立新的方法。根据观察数据系统评估类内治疗可互换性的框架： 1) 直接口服抗凝剂 (DOAC) 用于预防心房颤动或心房扑动中风，2) 二肽用于治疗 2 型糖尿病的肽酶 4 抑制剂 (DPP-4s)，3) 用于二级预防动脉粥样硬化性心血管 (CV) 疾病的高效他汀类药物，以及 4) 用于治疗 2 型糖尿病的钠-葡萄糖协同转运蛋白 2 抑制剂 (SGLT-2s) 这些是根据明确的标准选择的：D 部分受益人的高使用率、不确定性。关于类别内的治疗可互换性，替代方案之间的自付费用有足够的差异代理人以及有效衡量医疗保险索赔结果的能力我们纳入了具有强大先验的示例。针对（DPP-4 和 CV 结果）和（SGLT-2 和截肢）组内差异来表明我们可以重现预期的结果，以及其他差异不确定的结果（例如，DOAC 和缺血性该提案开始了一项有前途的高度新颖的工作，以切实可行地产生有效且批判性的结果。关于老年人广泛使用的药物类别中治疗可互换性的必要证据，可以作为为未来验证性研究奠定基础，并改善临床医学、患者治疗结果和公共卫生。