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: 10133498
• 负责人: Shirley Wang
• 金额: $ 36.56万
• 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 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10133498
• 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; comparative safety; 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.

当一种新药进入市场时，比较有效性证据通常仅由证据组成。 来自导致监管机构批准的随机临床试验(RCT)。老年人是主要的 药物和其他治疗药物的消费者，在随机临床试验中代表性不足。在.期间 在新药进入市场后的关键早期，来自随机对照试验的证据可能不能反映平均水平 对于实际接受治疗的患者类型的经验，以及在以下方面的“真实世界”经验不足 用于可靠证据生成的纵向医疗保健数据库。 在这个关键时刻，结合证据可以加强对新药净效益的理解 实际接受治疗的老年、病情较重的人群。然而，集成的适当方法 指导临床实践的上市前随机对照试验和上市后早期比较有效性证据尚未 但已被确认身份。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 来自上市前随机对照试验的个人水平数据，并创建由新的 使用医疗保险数据的药品和比较器。我们将评估结合证据的不同方法 根据随机对照试验生成的数据，这些数据来自联邦医疗保险中老年人日常护理中观察到的数据，这些证据是真实世界的 在新药上市的早期和后期都有经验。这些方法包括复杂的 加权和交叉设计综合方法结合了随机对照试验和“真实世界”数据中的信息。 具体来说，我们将研究：(1)如何创新应用方法结合个人层面的数据 根据上市前随机对照试验和早期上市后观察数据，加快对有效性和 新上市药物在随机对照试验中代表性不足的老年患者中的安全性？(2)如何 我们能否评估和理解上市前随机对照试验的治疗效果估计不同的原因 以及上市后早期的观测数据？ 该项目将产生一个框架，将上市前的随机对照试验和早期的上市后证据结合起来，作为 加速了解患有多种合并症的老年人的治疗效果的手段。使用 这一框架的实施将为老年医生提供早期的见解和临床指导，帮助他们在 患者在进入市场后不久。因为此项目中使用的方法旨在提供早期 反映实际接受治疗的患者的类型(和亚型)的平均有效性的证据 常规护理相对于试验参与者的平均疗效，该项目的影响将是 尤其是针对老年、病情较重的患者的新药，这些患者在试验中通常代表较少。