美国FDA推动老年用药证据优化与信息公开路径

FDA pathways to enhance evidence generation and information transparency for geriatric medication

摘要

随着人口老龄化进程的加快,老年人群的用药安全已成为全球公共卫生领域关注的焦点。本研究聚焦当前老年人群用药面临的三大挑战:临床试验中老年患者纳入不足、老年人群的药动学研究相对缺乏以及药品说明书中老年用药信息不完整,系统回顾了美国FDA为应对这些挑战构建的多层次政策支持体系。该体系重点涵盖优化临床试验资格标准、减少患者参与障碍、实施“药物试验快照”计划等关键举措,逐步完善了老年人群用药的证据生成与信息传递机制。结合我国国情,进一步在临床试验设计优化、药动学研究及药品信息透明化三大核心领域展开讨论。

Abstract

With the accelerating global of population aging, medication safety in older adults has become a global public health concern. This study focuses on three major challenges in geriatric pharmacotherapy: insufficient enrollment of elderly patients in clinical trials, a relative lack of pharmacokinetic studies in older populations, and incomplete geriatric use information in drug labeling. It then systematically reviews the multi-tiered policy support framework established by the U.S. Food and Drug Administration (FDA) to address these challenges. Key measures within this framework include optimizing clinical trial eligibility criteria, reducing barriers to patient participation, and implementing the “Drug Trials Snapshots” program, which have collectively improved evidence generation and information communication mechanisms for geriatric medication use. Based on China's national context, the study further discusses three core areas: clinical trial design optimization, pharmacokinetic research enhancement, and drug information transparency.

关键词

老年用药 / FDA / 临床试验 / 药品监管

Key words

geriatric pharmacotherapy / FDA / clinical trials / drug regulation

[1] GENSUS. The Graying of America: More Older Adults Than Kids by 2035[EB/OL].(2018-03-13)[2024-11-21].https://www.census.gov/library/stories/2018/03/graying-america.html.
[2] LIU Q, SCHWARTZ JB, SLATTUM PW, et al. Roadmap to 2030 for drug evaluation in older adults[J]. Clin Pharmacol Ther, 2022, 112(2): 210-223.
[3] VAN MARUM RJ. Underrepresentation of the elderly in clinical trials, time for action[J]. Br J Clin Pharmacol, 2020, 86(10): 2014-2016.
[4] JOHNNY LAU SW, HUANG Y, HSIEH J, et al. Participation of older adults in clinical trials for new drug applications and biologics license applications from 2010 through 2019[J]. JAMA Netw Open, 2022, 5(10): e2236149.
[5] NIH. Drug Research and Development for Adults Across the Older Age Span: Proceedings of a Workshop[EB/OL].(2021-01-22)[2025-05-02].https://www.ncbi.nlm.nih.gov/books/NBK575973.
[6] TOWNSLEY CA, CHAN KK, POND GR, et al. Understanding the attitudes of the elderly towards enrolment into cancer clinical trials[J]. BMC Cancer, 2006, 6: 34.
[7] IIJIMA H, SHIMIZU H, MORI-ANAI K, et al. Evaluation of age-related changes in teneligliptin pharmacokinetics in Japanese and European descent subjects using a physiologically based pharmacokinetic model[J]. Diabetes Ther, 2024, 15(4): 763-777.
[8] TAN YW, SUPPIAH SD, CHAN A, et al. Older adult and family caregiver experiences with prescription medication labels and their suggestions for label improvement[J]. Explor Res Clin Soc Pharm, 2021, 4: 100087.
[9] FDA. Study of drugs likely to be used in the Elderly[EB/OL].(1989)[2025-05-04].https://www.fda.gov/media/71114/download.
[10] FDA. E7 Studies in Support of Special Populations: Geriatrics[EB/OL].(1994)[2025-05-04].https://www.fda.gov/media/71317/download.
[11] FDA. E7 Studies in Support of Special Populations; Geriatrics; Questions and Answers[EB/OL].(2012)(2025-06-04).https://www.fda.gov/media/78220/download.
[12] US Government. PUBLIC LAW 112-144-JULY 9, 2012[EB/OL].(2012)[2025-02-07].https://www.fda.gov/regulatory-information/selected-amendments-fdc-act/food-and-drug-administration-safety-and-innovation-act-fdasia.
[13] FDA. FDA report: FDA action plan to enhance the collection and availability of demographic subgroup data[EB/OL].(2014)(2025-06-04).https://www.fda.gov/media/89307/download.
[14] FDA. Reports and Plans Mandated by FDARA[EB/OL].(2017)[2025-02-11].https://www.fda.gov/regulatory-information/fda-reauthorization-act-2017-fdara/reports-and-plans-mandated-fdara.
[15] FDA. Public Workshop: Evaluating Inclusion and Exclusion Criteria in Clinical Trials[EB/OL].(2018)[2025-05-19].https://www.fda.gov/media/134754/download.
[16] FDA.Enhancing the Diversity of Clinical Trial Populations-Eligibility Criteria, Enrollment Practices, and Trial Designs Guidance for Industry[EB/OL].(2020)[2025-05-21].https://www.fda.gov/media/127712/download.
[17] FDA. Inclusion of Older Adults in Cancer Clinical Trials-Final Guidance for Industry[EB/OL].(2022)[2025-05-27].https://www.fda.gov/media/156616/download.
[18] FDA. FDA Enhancing Clinical Study Diversity Workshop Report[EB/OL].(2023)[2025-03-15].https://www.fda.gov/media/179261/download.
[19] SUN ZX, ZHAO N, ZHAO X, et al. Application of physiologically based pharmacokinetic modeling of novel drugs approved by the U.S. food and drug administration[J]. Eur J Pharm Sci, 2024, 200: 106838.
[20] FDA. Pharmacokinetics in Patients with Impaired Hepatic Function: Study Design, Data Analysis, and Impact on Dosing and Labeling[EB/OL].(2003)[2025-04-14].https://www.fda.gov/media/71311/download.
[21] FDA. Pharmacokinetics in Patients with Impaired Renal Function-Study Design, Data Analysis, and Impact on Dosing Guidance for Industry[EB/OL].(2024)[2025-04-18].https://www.fda.gov/media/78573/download.
[22] FDA. New Drug and Antibiotic Regulations[EB/OL].(1985)[2025-04-21].https://www.fda.gov/science-research/clinical-trials-and-human-subject-protection/new-drug-and-antibiotic-regulations.
[23] FDA. Format and Content of the Clinical and Statistical Sections of an Application[EB/OL].(1988)[2025-04-24].https://www.fda.gov/media/71436/download.
[24] FDA. Investigational New Drug Applications and New Drug Applications[EB/OL].(1998)[2025-05-01].https://www.fda.gov/science-research/clinical-trials-and-human-subject-protection/investigational-new-drug-applications-and-new-drug-applications-2111998.
[25] FDA. Drug Trials Snapshots[EB/OL].(2015)[2025-05-04].https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots.
[26] U.S. Government Publishing Office. 62 FR 45313-Specific Requirements on Content and Format of Labeling for Human Prescription Drugs; Addition of “Geriatric Use” Subsection in the Labeling[EB/OL].(1997)[2025-05-08].https://www.federalregister.gov/documents/1997/08/27/97-22701/specific-requirements-on-content-and-format-of-labeling-for-human-prescription-drugs-addition-of.
[27] FDA. Guidance for Industry: Content and Format for Geriatric Labeling[EB/OL].(2001)[2025-05-13].https://www.fda.gov/media/72141/download.
[28] FDA. Geriatric Information in Human Prescription Drug and Biological Product Labeling Guidance for Industry[EB/OL].(2020)[2025-05-18].https://www.fda.gov/media/142162/download.
[29] FDA. History of FDA guidance on drug evaluation in older adult patients[EB/OL].(2021)[2025-05-29].https://www.fda.gov/media/147956/download.
[30] GRIMSTEIN M, YANG Y, ZHANG XY, et al. Physiologically based pharmacokinetic modeling in regulatory science: an update from the U.S. food and drug administration's office of clinical pharmacology[J]. J Pharm Sci, 2019, 108(1): 21-25.
[31] FDA. Impact Story: Supporting Drug Development Through Physiologically Based Pharmacokinetic Modeling[EB/OL].(2025-01-27)[2025-06-14].https://www.fda.gov/drugs/regulatory-science-action/impact-story-supporting-drug-development-through-physiologically-based-pharmacokinetic-modeling.
[32] 国家药品监督管理局药品审评中心. 生理药代动力学模型在儿科人群药物研发中应用的技术指导原则[EB/OL].(2023)[2025-06-17].https://www.cde.org.cn/zdyz/downloadAtt?idCODE=372dcccb234979069f5f922d6d6068fa.
[33] 丁静, 徐杨, 杨悦, 等. 美国FDA批准的新药在临床试验中老年人群纳入情况分析[J]. 中国新药杂志, 2026, 35(5): 449-454.
[34] 尉海波, 杨悦. 欧盟老年用药科学监管策略与制度分析[J]. 中国医药导刊, 2025, 27(8): 753-759.

基金资助

药品监管科学全国重点实验室课题资助项目(2023SKLDRS0141)