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

• 批准号: 10370353
• 负责人: Tobias Gerhard
• 金额: $ 60.8万
• 依托单位: RUTGERS BIOMEDICAL/HEALTH SCIENCES-RBHS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10370353
• 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 Name; 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; Process; Public Health; Randomized Controlled Trials; Research; Research Design; Risk; Secondary Prevention; Sodium; Stroke prevention; Structure; Therapeutic; Uncertainty; Update; Validation; Variant; Withdrawal; Work; atorvastatin; base; 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

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.

尽管几乎完全没有来自正面随机对照试验的足够数据，但 治疗指南和处方药保险配置通常会考虑在内 药物类别同样有效且同样安全。但是，关于治疗的假设不正确 交换性使患者暴露于次优治疗和不良临床结果，尤其是年龄较大 成年人，受到慢性疾病的影响不成比例的，是人均消费者的 处方药。尽管具有重大的临床和经济影响，但治疗性交换性 在没有可行的当前解决方案的情况下，仍然非常了解并代表一个问题。因此，我们 提出一种新型且可行的方法，可以评估同一级药物的治疗性交换性。 拟议的研究将利用Medicare D部分的结构创建的自然实验 药物福利和D部分计划从制造商那里获得的可变财务激励措施。由于计划 - 特定的配方管理策略，D部分注册会启动一种新药物通常面对 同一类中替代药物的自付费用不同。自付费用的差异 在数百个D部分计划中的替代同类药物中，将作为工具变量 （IVS）。因为这些经济激励措施严重影响了一种班级的一种药物而不是另一种药物 独立于患者的临床特征（如强的初步数据所证明），他们准备了 有效的IV估计。主要病历和死亡原因的结果验证 国家死亡指数进一步改善了该研究的严格性。使用> 2200万Medicare受益人的现有数据，拟议的研究将研究4个精心选择的药物类别，以建立新的方法论 从观察数据中系统地评估课堂内治疗性交换性的框架： 1）直接口服抗凝剂（DOAC）用于预防房颤或房间颤动，2）二肽基 2型糖尿病的肽酶4抑制剂（DPP-4S），3）高效力汀类药物用于预防动脉粥样硬化心血管疾病（CV）疾病，4）钠 - 葡萄糖co-Co-Transporter-2 糖尿病。这些是根据明确标准选择的：D部分受益人的高使用率，不确定性 关于班级的热交换性，替代方案之间有足够的自付成本差异 代理商以及有效衡量Medicare索赔结果的能力。我们包括了有很强先验的例子 反对（DPP-4和CV结果）和（SGLT-2S和截肢）的类差异，以表明我们 可以再现预期的发现，而其他差异不确定的发现（例如，DOAC和缺血性 中风）。该提议开始了一项高度有希望的小说工作，以可行地产生有效和批判性 需要证据证明老年人中广泛使用药物类别中的热交换性，作为 未来确认研究的基础，改善临床医学，患者结果和公共卫生。