Behavioral and cognitive outcomes for clinical trials in children with neurofibromatosis type 1
Behavioral and cognitive outcomes for clinical trials in children with neurofibromatosis type 1
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DOI：
10.1212/wnl.0000000000002118
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发表时间：
2016-01-12
期刊：
影响因子：
9.9
通讯作者：
Moll, Henriette A.
中科院分区：
文献类型：
--
作者：
van der Vaart, Thijs;Rietman, Andre B.;Moll, Henriette A.
目的：通过分析与参照组相比的缺陷程度、重测信度以及分数之间的相关性，评价认知和行为结果测量在1型神经纤维瘤病(NF1)临床试验中的适用性。方法：对辛伐他汀治疗1型神经纤维瘤病患者认知缺陷和行为问题(NF1-SIMCODA)试验的数据进行分析，这是一项辛伐他汀治疗NF1儿童认知缺陷和行为问题的随机安慰剂对照试验。将结果指标与年龄相关的参照组进行比较，以确定功能障碍的领域。计算安慰剂组在测量前后的皮尔逊相关系数，以评估重测的可靠性。结果：总体智力(-1.1 SD)、雷伊复杂图形测验延迟回忆(-2.0 SD)、注意问题(-1.2 SD)和社会问题(-1.1 SD)与参照组的平均分偏差最大。韦氏量表(r>；0.88)的长期重测信度较好，而其他神经心理学测验(r范围0.52~0.81)和儿童行为量表各子量表(r范围0.40~0.79)的重测信度较差。相关结构显示，行为和认知在结果测量中有两个较强的成分，这些成分之间没有相关性。心理社会生活质量得分与行为问题密切相关，与认知缺陷相关性较小。结论：NF1儿童在多个领域表现出明显的缺陷。在为期一年的试验期内，许多结果指标显示出弱的重测相关性。认知和行为结果是相辅相成的。这项分析表明，在NF1的临床试验中，有必要在各种认知和行为领域纳入可靠的结果衡量标准。
Objective:To evaluate the appropriateness of cognitive and behavioral outcome measures in clinical trials in neurofibromatosis type 1 (NF1) by analyzing the degree of deficits compared to reference groups, test-retest reliability, and how scores correlate between outcome measures.Methods:Data were analyzed from the Simvastatin for cognitive deficits and behavioral problems in patients with neurofibromatosis type 1 (NF1-SIMCODA) trial, a randomized placebo-controlled trial of simvastatin for cognitive deficits and behavioral problems in children with NF1. Outcome measures were compared with age-specific reference groups to identify domains of dysfunction. Pearson r was computed for before and after measurements within the placebo group to assess test-retest reliability. Principal component analysis was used to identify the internal structure in the outcome data.Results:Strongest mean score deviations from the reference groups were observed for full-scale intelligence (-1.1 SD), Rey Complex Figure Test delayed recall (-2.0 SD), attention problems (-1.2 SD), and social problems (-1.1 SD). Long-term test-retest reliability were excellent for Wechsler scales (r > 0.88), but poor to moderate for other neuropsychological tests (r range 0.52-0.81) and Child Behavioral Checklist subscales (r range 0.40-0.79). The correlation structure revealed 2 strong components in the outcome measures behavior and cognition, with no correlation between these components. Scores on psychosocial quality of life correlate strongly with behavioral problems and less with cognitive deficits.Conclusions:Children with NF1 show distinct deficits in multiple domains. Many outcome measures showed weak test-retest correlations over the 1-year trial period. Cognitive and behavioral outcomes are complementary. This analysis demonstrates the need to include reliable outcome measures on a variety of cognitive and behavioral domains in clinical trials for NF1.