未来已来：阿尔茨海默病基于模型的临床试验设计
The future is now: model-based clinical trial design for Alzheimer's disease.
作者信息
Romero K, Ito K, Rogers J A, Polhamus D, Qiu R, Stephenson D, Mohs R, Lalonde R, Sinha V, Wang Y, Brown D, Isaac M, Vamvakas S, Hemmings R, Pani L, Bain L J, Corrigan B
机构信息
Critical Path Institute, Tucson, Arizona, USA.
出版信息
Clin Pharmacol Ther. 2015 Mar;97(3):210-4. doi: 10.1002/cpt.16. Epub 2014 Dec 27.
Abstract
Failures in trials for Alzheimer's disease (AD) may be attributable to inadequate dosing, population selection, drug inefficacy, or insufficient design optimization. The Coalition Against Major Diseases (CAMD) was formed in 2008 to develop drug development tools (DDT) to expedite drug development for AD and Parkinson's disease. CAMD led a process that successfully advanced a clinical trial simulation (CTS) tool for AD through the formal regulatory review process at the US Food and Drug Administration (FDA) and European Medicines Agency (EMA).
摘要
阿尔茨海默病（AD）试验的失败可能归因于给药剂量不足、人群选择不当、药物无效或设计优化不足。抗重大疾病联盟（CAMD）成立于2008年，旨在开发药物研发工具（DDT），以加速AD和帕金森病的药物研发。CAMD主导了一个过程，成功地将一种用于AD的临床试验模拟（CTS）工具推进到美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）的正式监管审查程序中。
相似文献
1
The future is now: model-based clinical trial design for Alzheimer's disease.未来已来：阿尔茨海默病基于模型的临床试验设计
Clin Pharmacol Ther. 2015 Mar;97(3):210-4. doi: 10.1002/cpt.16. Epub 2014 Dec 27.
2
Approval of Cancer Drugs With Uncertain Therapeutic Value: A Comparison of Regulatory Decisions in Europe and the United States.具有不确定治疗价值的癌症药物的批准：欧洲和美国的监管决策比较。
Milbank Q. 2020 Dec;98(4):1219-1256. doi: 10.1111/1468-0009.12476. Epub 2020 Oct 6.
3
The approval of Aduhelm risks eroding public trust in Alzheimer research and the FDA.阿杜海姆（Aduhelm）的获批有削弱公众对阿尔茨海默病研究及美国食品药品监督管理局（FDA）信任的风险。
Nat Rev Neurol. 2021 Sep;17(9):523-524. doi: 10.1038/s41582-021-00540-6.
4
Advancing Alzheimer's disease drug review as a national priority.将推进阿尔茨海默病药物审查作为国家优先事项。
Alzheimers Dement. 2009 Mar;5(2):180-1. doi: 10.1016/j.jalz.2008.08.007.
5
Controversial Alzheimer's drug approval could affect other diseases.有争议的阿尔茨海默病药物获批可能会影响其他疾病。
Nature. 2021 Jul;595(7866):162-163. doi: 10.1038/d41586-021-01763-9.
6
Development of Novel Pharmaceutical Agents for Alzheimer's Disease: The Impact of Regulatory Initiatives in Japan and the United States.用于阿尔茨海默病的新型药物制剂的研发：日本和美国监管举措的影响。
Clin Ther. 2015 Aug;37(8):1652-60. doi: 10.1016/j.clinthera.2015.02.024. Epub 2015 Mar 21.
7
The US Food and Drug Administration's use of regular approval for cancer drugs based on single-arm studies: implications for subsequent evidence generation.美国食品药品监督管理局基于单臂研究对癌症药物进行常规批准的情况：对后续证据生成的影响。
Ann Oncol. 2018 Mar 1;29(3):527-529. doi: 10.1093/annonc/mdy008.
8
Communicating with the FDA: the "third rail" of a new model for drug development.与美国食品药品监督管理局沟通：药物研发新模式的“高压线”
J Clin Pharmacol. 2008 Feb;48(2):144-5. doi: 10.1177/0091270007313560.
9
The evaluation of disease modifying therapies in Alzheimer's disease: a regulatory viewpoint.阿尔茨海默病疾病修饰疗法的评估：监管视角
Stat Med. 2004 Jan 30;23(2):305-14. doi: 10.1002/sim.1718.
10
Characteristics of orphan drug applications that fail to achieve marketing approval in the USA.美国未获得营销批准的孤儿药申请的特征。
Drug Discov Today. 2011 Jan;16(1-2):73-80. doi: 10.1016/j.drudis.2010.11.006. Epub 2010 Nov 20.
引用本文的文献
1
The Potential of Disease Progression Modeling to Advance Clinical Development and Decision Making.疾病进展建模在推进临床开发和决策制定方面的潜力。
Clin Pharmacol Ther. 2025 Feb;117(2):343-352. doi: 10.1002/cpt.3467. Epub 2024 Oct 15.
2
Relationship between sex, APOE genotype, endocannabinoids and cognitive change in older adults with metabolic syndrome during a 3-year Mediterranean diet intervention.在一项为期 3 年的地中海饮食干预研究中，探讨了代谢综合征老年患者的性别、APOE 基因型、内源性大麻素与认知变化之间的关系。
Nutr J. 2024 Jun 12;23(1):61. doi: 10.1186/s12937-024-00966-w.
3
Transforming Drug Development for Neurological Disorders: Proceedings from a Multidisease Area Workshop.转化神经疾病药物研发：多疾病领域研讨会论文集
Neurotherapeutics. 2023 Oct;20(6):1682-1691. doi: 10.1007/s13311-023-01440-x. Epub 2023 Oct 12.
4
Rationale for the selection of dual primary endpoints in prevention studies of cognitively unimpaired individuals at genetic risk for developing symptoms of Alzheimer's disease.在预防认知正常、有阿尔茨海默病症状遗传风险的个体的研究中选择双重主要终点的理由。
Alzheimers Res Ther. 2023 Mar 6;15(1):45. doi: 10.1186/s13195-023-01183-z.
5
Early termination of pivotal trials in Alzheimer's disease-Preserving optimal value for participants and science.早期终止阿尔茨海默病关键试验-为参与者和科学保留最佳价值。
Alzheimers Dement. 2022 Oct;18(10):1980-1987. doi: 10.1002/alz.12605. Epub 2022 Feb 27.
6
The role of machine learning in clinical research: transforming the future of evidence generation.机器学习在临床研究中的作用：改变证据生成的未来。
Trials. 2021 Aug 16;22(1):537. doi: 10.1186/s13063-021-05489-x.
7
Pharmacometrics meets statistics-A synergy for modern drug development.药物代谢动力学与统计学的结合——现代药物研发的协同作用。
CPT Pharmacometrics Syst Pharmacol. 2021 Oct;10(10):1134-1149. doi: 10.1002/psp4.12696. Epub 2021 Aug 19.
8
Exploring the feasibility of using real-world data from a large clinical data research network to simulate clinical trials of Alzheimer's disease.探索利用大型临床数据研究网络中的真实世界数据来模拟阿尔茨海默病临床试验的可行性。
NPJ Digit Med. 2021 May 14;4(1):84. doi: 10.1038/s41746-021-00452-1.
9
Rates of Brain Atrophy Across Disease Stages in Familial Frontotemporal Dementia Associated With MAPT, GRN, and C9orf72 Pathogenic Variants.携带 MAPT、GRN 和 C9orf72 致病性变异的家族性额颞叶痴呆在疾病各阶段的脑萎缩率。
JAMA Netw Open. 2020 Oct 1;3(10):e2022847. doi: 10.1001/jamanetworkopen.2020.22847.
10
Standardized Data Structures in Rare Diseases: CDISC User Guides for Duchenne Muscular Dystrophy and Huntington's Disease.罕见病标准化数据结构：Duchenne 肌营养不良症和亨廷顿病的 CDISC 用户指南。
Clin Transl Sci. 2021 Jan;14(1):214-221. doi: 10.1111/cts.12845. Epub 2020 Aug 25.
本文引用的文献
1
Development of a unified clinical trial database for Alzheimer's disease.开发一个用于阿尔茨海默病的统一临床试验数据库。
Alzheimers Dement. 2015 Oct;11(10):1212-21. doi: 10.1016/j.jalz.2014.11.005. Epub 2015 Feb 9.
2
Combining patient-level and summary-level data for Alzheimer's disease modeling and simulation: a β regression meta-analysis.结合阿尔茨海默病建模和模拟的患者水平和汇总水平数据：β回归荟萃分析。
J Pharmacokinet Pharmacodyn. 2012 Oct;39(5):479-98. doi: 10.1007/s10928-012-9263-3. Epub 2012 Jul 21.
3
An improved model for disease progression in patients from the Alzheimer's disease neuroimaging initiative.阿尔茨海默病神经影像学倡议患者疾病进展的改进模型。
J Clin Pharmacol. 2012 May;52(5):629-44. doi: 10.1177/0091270011405497. Epub 2011 Jun 9.
4
A double-blind, delayed-start trial of rasagiline in Parkinson's disease (the ADAGIO study): prespecified and post-hoc analyses of the need for additional therapies, changes in UPDRS scores, and non-motor outcomes.一项针对帕金森病的雷沙吉兰双盲、延迟启动试验（ADAGIO 研究）：对额外治疗需求、UPDRS 评分变化和非运动结果的预先指定和事后分析。
Lancet Neurol. 2011 May;10(5):415-23. doi: 10.1016/S1474-4422(11)70073-4. Epub 2011 Apr 7.
5
The Coalition Against Major Diseases: developing tools for an integrated drug development process for Alzheimer's and Parkinson's diseases.重大疾病防治联盟：为阿尔茨海默病和帕金森病开发综合药物研发流程工具。
Clin Pharmacol Ther. 2009 Oct;86(4):365-7. doi: 10.1038/clpt.2009.165.
6
Methodologic aspects of a population pharmacodynamic model for cognitive effects in Alzheimer patients treated with tacrine.他克林治疗阿尔茨海默病患者认知效应的群体药效学模型的方法学方面
Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11466-70. doi: 10.1073/pnas.89.23.11466.
Zotero 插件