Methodological Issues in Randomized Clinical Trials for Prodromal Alzheimer's and Parkinson's Disease.
Methodological Issues in Randomized Clinical Trials for Prodromal Alzheimer's and Parkinson's Disease.
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DOI：
10.3389/fneur.2021.694329
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发表时间：
2021
影响因子：
3.4
通讯作者：
de Aquino CH
中科院分区：
文献类型：
--
作者：
de Aquino CH
阿尔茨海默病（AD）和帕金森病（PD）分别是第一和第二常见的神经退行性疾病。两者都是蛋白质病，具有不可阻挡的过程，并且没有批准的疾病修饰疗法。已经做出了大量努力来确定可以减缓AD和PD进展的干预措施;迄今为止，没有成功。生物标志物研究的进展改善了在症状发作之前对这些疾病风险个体的识别，识别临床前阶段，其中存在异常蛋白质积累但没有疾病的临床症状，以及前驱期，其中存在轻度症状但不能满足疾病的临床诊断标准。检测这些疾病的临床前和前驱阶段的能力鼓励了在早期阶段进行疾病修饰的临床试验，寻求减缓或防止表型转化为临床疾病。在这些阶段的临床试验有几个挑战，如合格人群的识别，生物标志物的适当选择，临床终点的定义，随访的持续时间和统计分析。本文旨在讨论AD和PD临床前和前驱期试验设计中的一些方法学挑战，批判性地回顾最近的研究，并讨论减轻试验设计中这些挑战的方法学方法。
Alzheimer's disease (AD) and Parkinson's disease (PD) are the first and second most common neurodegenerative disorders, respectively. Both are proteinopathies with inexorable courses and no approved disease-modifying therapies. A substantial effort has been made to identify interventions that could slow down the progression of AD and PD; to date, with no success. The advances in biomarker research improved the identification of individuals at risk for these disorders before symptom onset, recognizing the pre-clinical stage, in which there is abnormal protein accumulation but no clinical symptoms of the disease, and the prodromal stage, in which mild symptoms are present but the clinical diagnostic criteria for disease cannot be fulfilled. The ability to detect pre-clinical and prodromal stages of these diseases has encouraged clinical trials for disease-modification at earlier phases, seeking to slow or prevent phenoconversion into clinical disease. Clinical trials at these stages have several challenges, such as the identification of the eligible population, the appropriate choice of biomarkers, the definition of clinical endpoints, the duration of follow-up, and the statistical analysis. This article aims to discuss some of the methodological challenges in the design of trials for pre-clinical and prodromal phases of AD and PD, to critically review the recent studies, and to discuss methodological approaches to mitigate these challenges in trial design.
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DOI：
10.3233/jad-179901
发表时间：
2018
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
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影响因子：
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影响因子：
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作者：
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DOI：
10.1016/s0140-6736(16)31275-2
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2016-12-10
期刊：
Lancet (London, England)
影响因子：
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通讯作者：
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