Why has therapy development for dementia failed in the last two decades?
Why has therapy development for dementia failed in the last two decades?
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DOI：
10.1016/j.jalz.2015.12.003
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发表时间：
2016-01-01
影响因子：
14
通讯作者：
Middleton, Lefkos T.
中科院分区：
文献类型：
--
作者：
Gauthier, Serge;Albert, Marilyn;Middleton, Lefkos T.
在过去的二十年里，痴呆症药物的药物研究和开发（R&D）的成功率非常低。与其他治疗领域相比，正在开发的管道药物数量也很低。然而，在大多数试验中没有报告提前终止的理由。这些是英国卫生经济学办公室（OHE）最近发表的药品管道分析的关键发现。我们对主要挑战的理解包括：（1）在最常见而非家族性的迟发性痴呆的疾病分类学和基础生物学机制的复杂性方面存在重大知识差距;（2）低信噪比，尽管缺乏经验证的生物标志物作为进入和/或终点标准;（3）招募和保留，特别是在无症状和早期疾病阶段。一些当前和未来的战略，旨在改善药物开发的概述和讨论。(C)2016年阿尔茨海默氏症协会。爱思唯尔公司出版All rights reserved.
The success rate of the pharmaceutical research and development (R&D) for dementia drugs has been abysmally low, in the last two decades. Also low has been the number of pipeline drugs in development, compared to other therapy areas. However, the rationale of early terminations has not been reported in the majority of trials. These are key findings of the recently published pharmaceutical pipeline analysis by the UK-based Office of Health Economics (OHE). Our understanding of main challenges include (1) the significant gaps of knowledge in the nosology and complexity of the underpinning biological mechanisms of the commonest, not familial, forms of late onset dementias; (2) low signal-to-noise ratio, notwithstanding the lack of validated biomarkers as entry and/or end-point criteria; (3) recruitment and retention, particularly in the asymptomatic and early disease stages. A number of current and future strategies aimed at ameliorating drug development are outlined and discussed. (C) 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.