Understanding effectiveness of new drugs in older adults shortly after market entry

了解新药进入市场后不久对老年人的有效性

• 批准号: 9908033
• 负责人: Shirley Wang
• 金额: $ 36.41万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9908033
• 关键词: Adherence; Adult; Caring; Case Study; Characteristics; Clinical; Complex; Data; Databases; Effectiveness; Elderly; Future; Generations; Healthcare; Heterogeneity; Individual; Marketing; Measurement; Measures; Medicare; Methods; Outcome; Participant; Patients; Pattern; Pharmaceutical Preparations; Physicians; Population; Population Heterogeneity; Randomized Clinical Trials; Research; Research Personnel; Risk; Safety; Source; Techniques; Therapeutic; Time; Treatment Effectiveness; Weight; clinical development; clinical practice; clinical trial participant; cohort; comorbidity; comparative effectiveness; design; drug market; early experience; experience; inclusion criteria; innovation; insight; interest; novel therapeutics; older patient; patient population; post-market; prospective; routine care; tool; treatment effect

When a new drug enters the market, comparative effectiveness evidence is often comprised solely of evidence from the randomized clinical trials (RCTs) which led to regulatory agency approval. Older adults are major consumers of drugs and other therapeutics and underrepresented in randomized clinical trials. During the critical early period after a new drug enters the market, evidence from RCTs may not reflect the average experience for the types of patients actually treated and there is insufficient accrual of ‘real world’ experience in longitudinal healthcare databases for robust evidence generation. At this critical juncture, combining evidence can enhance understanding of net benefit of new drugs in the older, sicker populations who are actually treated in practice. However, appropriate methods for integrating pre-market RCT and early post-market comparative effectiveness evidence to guide clinical practice have not yet been identified. We will explore these issues in three case studies. For each case study, we will obtain individual level data from pre-market RCTs and create observational cohorts comprised of initiators of the new drug and comparator using Medicare data. We will evaluate different methods which combine evidence generated from RCT with ‘real world’ evidence from data observed in routine care of older adults in Medicare during early as well as later post-market experience with the new drugs. These methods include complex weighting as well as cross-design synthesis methods that combine information from RCT and ‘real world’ data. Specifically we will research: (1) How can innovative application of methods to combine individual-level data from pre-market RCTs and early post-market observational data accelerate understanding of effectiveness and safety of new to market medications in older patients who are typically underrepresented in RCTs? (2) How can we evaluate and understand reasons for differences in treatment effect estimates from pre-market RCTs and observational data in the early post-market time period? This project will produce a framework for combining pre-market RCT and early post-market evidence as a means to accelerate understanding of treatment effectiveness in older adults with multiple comorbidities. Use of this framework will provide early insights and clinical guidance to geriatricians on use of new drugs in their patients shortly after market entry. Because the methods used in this project are designed to provide early evidence that reflect average effectiveness in the types (and subtypes) of patients actually treated as part of routine care as opposed to average effectiveness in participants of a trial, the impact of this project will be particularly profound for new medications that target older, sicker patients typically underrepresented in trials.

当新药进入市场时，通常仅通过证据来完成比较有效性证据 从导致监管机构批准的随机临床试验（RCT）中。老年人是主要的 药物和其他治疗剂的消费者，在随机临床试验中的代表性不足。在 新药进入市场后的关键早期，RCT的证据可能不反映平均水平 实际治疗的患者类型的经验，“现实世界”经验的准确性不足 纵向医疗保健数据库，可用于稳健的证据产生。 在这个关键时刻，结合证据可以增强对新药净益处的理解 实际上在实践中实际接受治疗的年龄较大，患病的人群。但是，集成的适当方法 预市场RCT和早期市场后的比较有效性证据指导临床实践尚未 尚未确定。我们将在三个案例研究中探讨这些问题。对于每个案例研究，我们将获得 来自前市场RCT的个人级别数据，并创建了新的启动者的观察人群 使用Medicare数据的药物和比较器。我们将评估结合证据的不同方法 由RCT产生的，并从Medicare的老年人的常规护理中观察到的“现实世界”证据产生 在早期以及后来的新药后市场经验。这些方法包括复杂 加权以及结合RCT和“现实世界”数据信息的跨设计语法方法。 具体而言，我们将研究：（1）如何创新的方法结合个人级别数据 来自市场前RCT和市场后的观测数据，可以加速对有效性和的理解 在RCT中通常代表性不足的老年患者中新手药物的安全性？ （2）如何 我们可以评估和理解治疗效应估计的原因 以及在市场后早期期间的观察数据？ 该项目将产生一个框架，用于将前市场的RCT和早期市场证据相结合为 意味着要加快多种合并症老年人的治疗效果的理解。使用 此框架将为老年医生提供有关新药的早期见解和临床指导 市场进入后不久。因为该项目中使用的方法旨在提早提供 反映实际上被视为一部分的患者类型（和亚型）的平均效率的证据 常规护理而不是试验参与者的平均效率，该项目的影响将是 对于针对年龄较大，病患者的新药物通常在试验中代表性不足的新药物特别深刻。