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为什么治疗老年痴呆症的药物这么少?是方法让药物研发失败了吗?

Why so few drugs for Alzheimer's disease? Are methods failing drugs?

机构信息

Drug Design & Development Section, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.

出版信息

Curr Alzheimer Res. 2010 Nov;7(7):642-51. doi: 10.2174/156720510793499075.

Abstract

Recent studies of Alzheimer's disease (AD) and other neuropsychiatric drug developments raise questions whether failures of some drugs occur due to flaws in methods. In three case studies of recent AD drug development failures with phenserine, metrifonate, and tarenflurbil we identified methodological lapses able to account for the failures. Errors in complex systems such as drug developments are both almost inescapable due to human mistakes and most frequently hidden at the time of occurrence and thereafter. We propose preemptive error management as a preventive strategy to exclude or control error intrusions into neuropsychiatric drug developments. We illustrate the functions we anticipate for a preemptive error management preventive strategy with a checklist and identify the limitations of this aspect of the proposal with three drug examples. This strategy applies core scientific practices to insure the quality of data within the current context of AD drug development practices.

摘要

最近对阿尔茨海默病(AD)和其他神经精神药物开发的研究提出了这样一个问题,即某些药物的失败是否是由于方法上的缺陷所致。在对苯海索、美曲膦酯和他克林这三种最近 AD 药物开发失败的案例研究中,我们发现了一些能够解释失败的方法学缺陷。由于人为错误,复杂系统(如药物开发)中的错误几乎是不可避免的,而且在发生时和之后最常被隐藏。我们提出了先发制人的错误管理作为一种预防策略,以排除或控制错误侵入神经精神药物开发。我们用清单说明了我们预期的先发制人的错误管理预防策略的功能,并通过三个药物示例确定了该建议这一方面的局限性。该策略应用核心科学实践,以确保当前 AD 药物开发实践中数据的质量。

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本文引用的文献

1
Lost in translation: neuropsychiatric drug development.
Sci Transl Med. 2010 Dec 8;2(61):61rv6. doi: 10.1126/scitranslmed.3000446.
2
Phenserine efficacy in Alzheimer's disease.
J Alzheimers Dis. 2010;22(4):1201-8. doi: 10.3233/JAD-2010-101311.
3
Pharmacology. The puzzling rise and fall of a dark-horse Alzheimer's drug.
Science. 2010 Mar 12;327(5971):1309. doi: 10.1126/science.327.5971.1309.
5
Dimebon as a potential therapy for Alzheimer's disease.
CNS Spectr. 2009 Aug;14(8 Suppl 7):14-6; discussion 16-8. doi: 10.1017/s1092852900024913.
7
What we have learned from the Myriad trials.
J Nutr Health Aging. 2009 Apr;13(4):362-4. doi: 10.1007/s12603-009-0044-7.
8
Resurrecting clinical pharmacology as a context for Alzheimer disease drug development.
Curr Alzheimer Res. 2009 Feb;6(1):79-81. doi: 10.2174/156720509787313916.
9
The perils of Alzheimer's drug development.
Curr Alzheimer Res. 2009 Feb;6(1):77-8. doi: 10.2174/156720509787313871.
10
Neuropsychiatric clinical trials: should they accommodate real-world practices or set standards for clinical practices?
J Clin Psychopharmacol. 2009 Feb;29(1):56-64. doi: 10.1097/JCP.0b013e318192e2fa.

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