A randomized double-blind controlled trial of everolimus in individuals with PTEN mutations: Study design and statistical considerations.
A randomized double-blind controlled trial of everolimus in individuals with PTEN mutations: Study design and statistical considerations.
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依维莫司在PTEN突变个体中的随机双盲对照试验：研究设计和统计学考虑
DOI：
10.1016/j.conctc.2021.100733
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发表时间：
2021-03
影响因子：
1.5
通讯作者：
Sahin M
中科院分区：
文献类型：
--
作者：
Hardan AY;Jo B;Frazier TW;Klaas P;Busch RM;Dies KA;Filip-Dhima R;Snow AV;Eng C;Hanna R;Zhang B;Sahin M
这项随机、双盲对照试验旨在评价依维莫司与安慰剂相比的安全性，并通过标准化的神经认知和运动测量以及行为问卷来评估依维莫司与安慰剂相比对神经认知和行为的疗效。依维莫司的安全性特点是可控制的不良事件，通常是可逆的和非累积的。本研究的主要安全性终点是由于副作用导致的退出率，比较依维莫司和安慰剂。我们还试图确定不良事件的类型和严重程度的频率。主要疗效终点是通过两种方式计算的神经认知复合：1)工作记忆、处理速度和精细运动子测试的平均值；2)除加权2/3外，与上述相同的平均值，并根据所有其他可用的神经认知测试方法评估非语言能力，视觉运动技能，语言学习和接受和表达语言的额外领域的平均值，加权1/3。次要疗效终点考察了依维莫司对总体临床改善、自闭症症状、行为问题和适应能力的影响，这些影响是通过经过验证的标准化仪器测量的。我们预测，与安慰剂相比，依维莫司组的不良事件发生率将不超过10%，副作用的总体严重程度将是最小的。我们还预计，与服用安慰剂的患者相比，服用依维莫司的患者在复合神经认知指数上表现出更大的改善。
This randomized, double-blind controlled trial of everolimus in individuals with germline phosphatase and tensin homolog mutations (PTEN) was designed to evaluate the safety of everolimus compared with placebo and to evaluate the efficacy of everolimus on neurocognition and behavior compared to placebo as measured by standardized neurocognitive and motor measures as well as behavioral questionnaires. The safety profile of everolimus is characterized by manageable adverse events that are generally reversible and non-cumulative. The primary safety endpoint of this study was drop-out rate due to side effects, comparing everolimus versus placebo. We also sought to determine the frequency of adverse events by type and severity. The main efficacy endpoint was a neurocognitive composite computed in two ways: 1) an average for working memory, processing speed, and fine motor subtests; and 2) the same average as above except weighted 2/3, and an additional average based on all other available neurocognitive testing measures assessing the additional domains of nonverbal ability, visuomotor skills, verbal learning, and receptive and expressive language, weighted 1/3. Secondary efficacy endpoints examined the effect of everolimus on overall global clinical improvement, autism symptoms, behavioral problems, and adaptive abilities as measured by validated, standardized instruments. We predicted that the rate of adverse events would be no more than 10% higher in the everolimus group compared to placebo, and overall severity of side effects would be minimal. We also expected that individuals receiving everolimus would show more improvement, relative to those taking placebo, on the composite neurocognitive index.
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影响因子：
5.6
作者：
Martin, R;Sawrie, S;Kuzniekcy, R
通讯作者：
Kuzniekcy, R
影响因子：
17.1
作者：
Berry-Kravis, Elizabeth;Portes, Vincent Des;von Raison, Florian
通讯作者：
von Raison, Florian
DOI：
10.1111/j.1744-6171.1991.tb00509.x
发表时间：
1991-10-01
期刊：
Journal of child and adolescent psychiatric and mental health nursing
影响因子：
--
作者：
Garvey, C A;Gross, D;Freeman, L
通讯作者：
Freeman, L
影响因子：
5.2
作者：
Mester, Jessica L.;Tilot, Amanda K.;Eng, Charis
通讯作者：
Eng, Charis
影响因子：
8.8
作者：
Busch, Robyn M.;Chapin, Jessica S.;Eng, Charis
通讯作者：
Eng, Charis