Defining Disease Modifying Therapy for Alzheimer's Disease.
Defining Disease Modifying Therapy for Alzheimer's Disease.
复制标题
DOI：
10.14283/jpad.2017.12
复制
发表时间：
2017
影响因子：
--
通讯作者：
Fox N
中科院分区：
文献类型：
--
作者：
Cummings J;Fox N
迫切需要疾病修正疗法(DMT)来治疗越来越多的阿尔茨海默病(AD)患者或具有AD内在风险的患者。需要对DMT进行定义，以促进DMT药物的开发过程。这是关于DMT的定义和发展的科学状态的回顾。DMT是一种干预措施，通过干扰导致细胞死亡的疾病过程的潜在病理生理机制，在AD的临床进展中产生持久的变化。DMT疗效的证明是通过临床试验设计和生物标记物获得的。药物开发过程中疾病修改的证据基于试验设计，如交错开始和延迟停药，显示对病程或综合临床结果的持久影响，以及对疾病潜在病理生理过程产生影响的相关生物标记物证据。分析方法，如显示认知下降斜率的变化，随着时间的推移增加药物与安慰剂的差异，以及推迟疾病里程碑本身并不是决定性的，但支持疾病改善效果的存在。神经保护是一个相关的概念，其论证依赖于对疾病的修改。任何单一类型的证据本身都不足以证明疾病修改--一致性、稳健性和数据来源的多样性都将有助于说服利益相关者某一制剂是一种DMT。DMT的定义是其对导致细胞死亡的过程的持久影响。各种类型的数据可以用来支持疾病改变已经发生的假设。
Disease-modifying therapies (DMTs) are urgently needed to treat the growing number of individuals with Alzheimer’s disease (AD) or at immanent risk for AD. A definition of DMT is required to facilitate the process of DMT drug development. This is a review of the state of the science with regard to definition and development of DMTs. A DMT is as an intervention that produces an enduring change in the clinical progression of AD by interfering in the underlying pathophysiological mechanisms of the disease process that lead to cell death. Demonstration of DMT efficacy is garnered through clinical trial designs and biomarkers. Evidence of disease modification in the drug development process is based on trial designs such as staggered start and delayed withdrawal showing an enduring effect on disease course or on combined clinical outcomes and correlated biomarker evidence of an effect on the underlying pathophysiological processes of the disease. Analytic approaches such as showing change in slope of cognitive decline, increasing drug-placebo difference over time, and delay of disease milestones are not conclusive by themselves but support the presence of a disease modifying effect. Neuroprotection is a related concept whose demonstration depends on substantiating disease modification. No single type of evidence in itself is sufficient to prove disease modification – consistency, robustness, and variety of sources of data will all contribute to convincing stakeholders that an agent is a DMT. DMT is defined by its enduring effect on processes leading to cell death. A variety of types of data can be used to support the hypothesis that disease modification has occurred.
登录
查看更多内容
DOI：
10.1016/j.jalz.2011.03.005
发表时间：
2011-05
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
McKhann GM;Knopman DS;Chertkow H;Hyman BT;Jack CR Jr;Kawas CH;Klunk WE;Koroshetz WJ;Manly JJ;Mayeux R;Mohs RC;Morris JC;Rossor MN;Scheltens P;Carrillo MC;Thies B;Weintraub S;Phelps CH
通讯作者：
Phelps CH
影响因子：
2.2
作者：
Amur, Shashi G.;Sanyal, Sarmistha;Buckman-Garner, ShaAvhree Y.
通讯作者：
Buckman-Garner, ShaAvhree Y.
影响因子：
5.4
作者：
Blennow, Kaj;Zetterberg, Henrik;Fagan, Anne M.
通讯作者：
Fagan, Anne M.
影响因子：
168.9
作者：
Holmes, Clive;Boche, Delphine;Nicoll, James A. R.
通讯作者：
Nicoll, James A. R.
影响因子：
14
作者：
Cummings, Jeffrey L.
通讯作者：
Cummings, Jeffrey L.