Baseline factors predicting placebo response to treatment in children and adolescents with autism spectrum disorders: a multisite randomized clinical trial.
Baseline factors predicting placebo response to treatment in children and adolescents with autism spectrum disorders: a multisite randomized clinical trial.
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DOI：
10.1001/jamapediatrics.2013.2698
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发表时间：
2013-11
期刊：
影响因子：
26.1
通讯作者：
Hirtz D
中科院分区：
文献类型：
--
作者：
King BH;Dukes K;Donnelly CL;Sikich L;McCracken JT;Scahill L;Hollander E;Bregman JD;Anagnostou E;Robinson F;Sullivan L;Hirtz D
差异预测安慰剂与活性药物反应可能性的因素的发现可能会对这一人群的研究设计产生重大影响。在一项针对患有自闭症谱系障碍的儿童和青少年的大型随机临床试验中，确定干预反应可能的非特异性基线预测因素。氢溴酸西酞普兰治疗患有自闭症谱系障碍和突出重复行为的儿童和青少年的随机临床试验。根据最终结果检查研究开始时的基线数据，以确定是否可以识别反应预测因子。来自 6 个学术中心的总共 149 名 5 至 17 岁儿童和青少年（平均 [SD] 年龄，9.4 [3.1] 岁）被随机分配到西酞普兰组 (n = 73) 或安慰剂组 (n = 76)。参与者患有自闭症、阿斯伯格综合症或广泛性发育障碍（未另有说明）；在临床总体印象-严重程度量表中，疾病严重程度评级为中等或以上；使用改良版儿童耶鲁-布朗强迫量表测量的强迫行为得分为中等或中等以上。使用西酞普兰（10 mg/5 mL）或安慰剂治疗十二周。西酞普兰的平均（SD）最大剂量为每日口服 16.5（6.5）mg（最大剂量，20 mg/d）。积极反应被定义为在第 12 周时临床总体印象改善量表的分数至少有很大改善。基线测量包括人口统计（性别、年龄、体重和青春期状态）、临床和家庭测量。临床变量包括基线疾病严重程度评级（异常行为检查表、儿童和青少年症状量表、瓦恩兰适应性行为量表、重复行为量表修订版和儿童耶鲁-布朗强迫量表）。家庭措施包括护理人员压力问卷。确定了几个反应的基线预测因子，主成分分析得出了 3 个综合指标（破坏性行为、自闭症/情绪和护理人员紧张），这些指标显着预测了第 12 周时的反应。具体来说，如果安慰剂组的参与者在第 12 周时在 3 个综合指标中的每一个上表现出更多症状，则安慰剂组的参与者比西酞普兰组的参与者做出反应的可能性显着降低，并且他们成为反应者的可能性至少低 2 倍。该分析提出了可能有助于预测和潜在减轻自闭症谱系障碍儿童和青少年随机临床试验中非特异性反应的策略。 ClinicalTrials.gov 标识符：NCT00086645
The finding of factors that differentially predict the likelihood of response to placebo over that of an active drug could have a significant impact on study design in this population. To identify possible nonspecific, baseline predictors of response to intervention in a large randomized clinical trial of children and adolescents with autism spectrum disorders. Randomized clinical trial of citalopram hydrobromide for children and adolescents with autism spectrum disorders and prominent repetitive behavior. Baseline data at study entry were examined with respect to final outcome to determine if response predictors could be identified. A total of 149 children and adolescents 5 to 17 years of age (mean [SD] age, 9.4 [3.1] years) from 6 academic centers were randomly assigned to citalopram (n = 73) or placebo (n = 76). Participants had autistic disorder, Asperger syndrome, or pervasive developmental disorder, not otherwise specified; had illness severity ratings that were moderate or more than moderate on the Clinical Global Impression–Severity scale; and scored moderate or more than moderate on compulsive behaviors measured with the modified Children’s Yale-Brown Obsessive-Compulsive Scale. Twelve weeks of treatment with citalopram (10 mg/5 mL) or placebo. The mean (SD) maximum dose of citalopram was 16.5 (6.5) mg by mouth daily (maximum dose, 20 mg/d). A positive response was defined as having a score of at least much improved on the Clinical Global Impression–Improvement scale at week 12. Baseline measures included demographic (sex, age, weight, and pubertal status), clinical, and family measures. Clinical variables included baseline illness severity ratings (the Aberrant Behavior Checklist, the Child and Adolescent Symptom Inventory, the Vineland Adaptive Behavior Scales, the Repetitive Behavior Scale–Revised, and the Children’s Yale-Brown Obsessive-Compulsive Scale). Family measures included the Caregiver Strain Questionnaire. Several baseline predictors of response were identified, and a principal component analysis yielded 3 composite measures (disruptive behavior, autism/mood, and caregiver strain) that significantly predicted response at week 12. Specifically, participants in the placebo group were significantly less likely than participants in the citalopram group to respond at week 12 if they entered the study more symptomatic on each of the 3 composite measures, and they were at least 2 times less likely to be responders. This analysis suggests strategies that may be useful in anticipating and potentially mitigating the nonspecific response in randomized clinical trials of children and adolescents with autism spectrum disorders. clinicaltrials.gov Identifier: NCT00086645