【佳学基因检测】临床试验中认知终点的可重复性：1 型神经纤维瘤病的教训

肿瘤基因检测哪家机构最好导读

根据肿瘤基因检测全面性的标准与实施方案知悉《Ann Clin Transl Neurol》在. 2019 Dec;6(12):2555-2565.发表了一篇题目为《临床试验中认知终点的可重复性：1 型神经纤维瘤病的教训》肿瘤靶向药物治疗基因检测临床研究文章。该研究由Jonathan M Payne, Stephen J C Hearps, Karin S Walsh, Iris Paltin, Belinda Barton, Nicole J Ullrich, Kristina M Haebich, David Coghill, Gerard A Gioia, Alan Cantor, Gary Cutter, James H Tonsgard, David Viskochil, Celiane Rey-Casserly, Elizabeth K Schorry, Joseph D Ackerson, Laura Klesse, Michael J Fisher, David H Gutmann, Tena Rosser, Roger J Packer, Bruce Korf, Maria T Acosta, Kathryn N North, NF Clinical Trials Consortium等完成。促进了肿瘤的精准治疗与个性化用药的发展，进一步强调了基因信息检测与分析的重要性。

肿瘤靶向药物及精准治疗临床研究内容关键词：

BRCA,卵巢癌,测试标准

肿瘤靶向治疗基因检测临床应用结果

基因解码基因检测的研究目的：在理解神经发育障碍中认知缺陷的分子机制方面的快速发展增加了对基于机制的靶向治疗的期望。然而，从临床前模型到人体临床试验的转化已被证明具有挑战性。认知终点的可重复性差可能为这一发现提供了一种解释。基因解码基因检测通过检查测量的重测可靠性和应用数据简化技术来提高可重复性，检查认知基因解码基因检测的研究结果对 1 型神经纤维瘤病 (NF1) 儿童临床试验的适用性。基因解码基因检测的研究方法：数据分析来自 STARS 临床试验 ( n = 146)，洛伐他汀的多中心双盲安慰剂对照 II 期试验，由 NF 临床试验联盟进行。在安慰剂组的神经心理学终点的表演前和表演后（16 周间隔）之间产生了组内相关系数，以确定重测信度。验证性因素分析用于将数据减少到认知领域并解释测量误差。基因解码基因检测的研究结果：重测信度变化很大，大多数终点显示出不可接受的低再现性。数据缩减证实了四个不同的神经心理学领域：执行功能/注意力、视觉空间能力、记忆和行为。潜在因素的重测信度提高到临床试验可接受的水平。基因解码基因检测模型的适用性和实用性通过重新分析的疗效数据中的同质效应大小得到证明。解释：这些数据表明，单个观察到的终点不适合确定疗效，部分原因是临床试验中认知基因解码基因检测的研究结果的重测可靠性差神经发育障碍。概述了提高可重复性的建议，以指导未来的试验设计。

肿瘤发生与复发转移国际数据库描述：

Objective: Rapid developments in understanding the molecular mechanisms underlying cognitive deficits in neurodevelopmental disorders have increased expectations for targeted, mechanism-based treatments. However, translation from preclinical models to human clinical trials has proven challenging. Poor reproducibility of cognitive endpoints may provide one explanation for this finding. We examined the suitability of cognitive outcomes for clinical trials in children with neurofibromatosis type 1 (NF1) by examining test-retest reliability of the measures and the application of data reduction techniques to improve reproducibility.Methods: Data were analyzed from the STARS clinical trial (n = 146), a multi-center double-blind placebo-controlled phase II trial of lovastatin, conducted by the NF Clinical Trials Consortium. Intra-class correlation coefficients were generated between pre- and post-performances (16-week interval) on neuropsychological endpoints in the placebo group to determine test-retest reliabilities. Confirmatory factor analysis was used to reduce data into cognitive domains and account for measurement error.Results: Test-retest reliabilities were highly variable, with most endpoints demonstrating unacceptably low reproducibility. Data reduction confirmed four distinct neuropsychological domains: executive functioning/attention, visuospatial ability, memory, and behavior. Test-retest reliabilities of latent factors improved to acceptable levels for clinical trials. Applicability and utility of our model was demonstrated by homogeneous effect sizes in the reanalyzed efficacy data.Interpretation: These data demonstrate that single observed endpoints are not appropriate to determine efficacy, partly accounting for the poor test-retest reliability of cognitive outcomes in clinical trials in neurodevelopmental disorders. Recommendations to improve reproducibility are outlined to guide future trial design.