Registry of Senior Australians (ROSA) South Australian Health and Medical Research Institute Adelaide South Australia Australia.
Division of Health Sciences University of South Australia Adelaide Australia.
J Am Heart Assoc. 2020 Nov 3;9(21):e016936. doi: 10.1161/JAHA.120.016936. Epub 2020 Oct 26.
Background Underrepresentation of older people in clinical trials remains. This study aimed to examine the inclusion of older people and associated safety and efficacy reports from clinical trials of new molecular entities for cardiovascular disease indications since commencement of the US Food and Drug Administration Drug Trial Snapshot (DTS) Program. The DTS provides concise information on participants included in clinical trials supporting US Food and Drug Administration approval of new drugs. Methods and Results A cross-sectional analysis between January 1, 2015 and April 30, 2019 of DTS data including approval date, indication, number of trials and participants, age distribution, efficacy, and safety statements was conducted. Participation-to-prevalence ratio (PPR) was used to describe representation of older participants in trials relative to disease population. Efficacy and safety statements regarding age were compared with drug prescribing information. A total of 72 079 participants from 10 DTS reports were identified and 39 625 (55.0%) were aged ≥65 years old. Overall, 63.6% of cardiovascular disease DTS reports were representative of people aged ≥65 years old for specific cardiovascular disease conditions. Underrepresentation was observed in 4 DTS: 2 for heart failure (PPR 0.48 and 0.62), 1 for pulmonary arterial hypertension (PPR 0.72), and 1 for venous thromboembolism (PPR 0.38). Participants in clinical trials for new drugs for the treatment of atrial fibrillation (PPR 0.99 and 1.21) and hypercholesterolemia (PPR 0.84 and 0.97) were reflective of the older population for these diseases. An increased risk of adverse events in older participants was reported in 40% DTS safety statements but no differences were reported in the drug product information. Conclusions Despite the fact that >60% of cardiovascular disease trial participants for new molecular entities included in the DTS program were representative of the older population in real-world clinical practice, concerns remain for conditions including heart failure or venous thromboembolism. Drug product information safety statements regarding age differences in adverse events were not reflective of trial findings. An increased directive is needed to facilitate the generation of real-world evidence and appropriate reporting within drug product information for these potentially at-risk patient populations.
临床试验中老年人代表性不足的情况仍然存在。本研究旨在检查自美国食品和药物管理局（FDA）药物试验快照（DTS）计划启动以来，新分子实体治疗心血管疾病适应证临床试验中老年人的纳入情况，以及相关的安全性和疗效报告。DTS 提供了支持 FDA 批准新药的临床试验中参与者的简明信息。
对 2015 年 1 月 1 日至 2019 年 4 月 30 日期间的 DTS 数据进行了横断面分析，包括批准日期、适应证、试验和参与者数量、年龄分布、疗效和安全性声明。使用参与率与患病率比值（PPR）来描述试验中老年人的代表性与疾病人群的关系。比较了关于年龄的疗效和安全性声明与药物说明书信息。共从 10 份 DTS 报告中确定了 72079 名参与者，其中 39625 名（55.0%）年龄≥65 岁。总体而言，63.6%的心血管疾病 DTS 报告对特定心血管疾病状况下≥65 岁的人群具有代表性。有 4 份 DTS 报告显示代表性不足：心力衰竭 2 份（PPR 分别为 0.48 和 0.62），肺动脉高压 1 份（PPR 为 0.72），静脉血栓栓塞症 1 份（PPR 为 0.38）。治疗心房颤动（PPR 分别为 0.99 和 1.21）和高胆固醇血症（PPR 分别为 0.84 和 0.97）的新药临床试验中，参与者反映了这些疾病中老年人的情况。40%的 DTS 安全性声明报告了老年参与者发生不良事件的风险增加，但药物产品信息中未报告差异。
尽管 DTS 计划中纳入的新分子实体心血管疾病试验中超过 60%的参与者代表了真实世界临床实践中的老年人群，但仍有一些问题需要关注，包括心力衰竭或静脉血栓栓塞症。药物产品信息中关于不良事件年龄差异的安全性声明与试验结果不符。需要增加指令，以促进这些潜在高危患者群体的真实世界证据的生成和在药物产品信息中的适当报告。
