Toward Outcome Measurement of Anxiety in Youth with Autism Spectrum Disorders

自闭症谱系障碍青少年焦虑的结果测量

• 批准号: 8650951
• 负责人: Lawrence D. Scahill
• 金额: $ 60.43万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-15 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8650951
• 关键词: Adolescent; Affect; Age; American; Anxiety; Behavior; Child; Childhood; Clinic; Clinic Visits; Clinical Trials; Cognitive deficits; DSM-IV; Data; Development; Disabled Persons; Equipment and supply inventories; Focus Groups; Frustration; Future; Gender; Grant; Heart Rate; Interview; Investigation; Label; Language Disorders; Measurement; Measures; Medical; Methods; Modification; Monograph; NIH Program Announcements; Outcome; Outcome Measure; Parenting behavior; Parents; Participant; Patient Outcomes Assessments; Pattern; Persons; Pharmaceutical Preparations; Physiological; Reading; Recruitment Activity; Research; Research Personnel; Respondent; Rest; Sampling; Secure; Site; Social Behavior; Structure; Subgroup; Surveys; Symptoms; Testing; Validity and Reliability; Withdrawal; Youth; autism spectrum disorder; base; developmentally disabled; disability; drug development; heart rate variability; instrument; product development; psychosocial; social; web site

DESCRIPTION (provided by applicant): This four-year multisite project will advance outcome measurement of anxiety in future clinical trials in youth with autism spectrum disorders (ASDs). Program announcement (PAR-11-045) declares that the dearth of outcome measures in developmentally disabled populations is a major impediment for drug research in developmentally disabled populations. Impairing anxiety is common in youth with ASDs and a plausible treatment target, but poorly studied (White et al., 2009; van Steensel et al., 2011; King et al., 2009). There are well-accepted outcome measures for anxiety in typically developing youth (RUPP Anxiety Group, 2001; Walkup et al., 2008). Given the language and cognitive deficits in ASDs, these measures are not suitable for youth with ASDs without modification. The need for outcome measures for anxiety in youth with ASDs has also been noted by consumer groups (www. autismspeaks.org). We have assembled an outstanding team of investigators and consultants to develop a parent-rated and a clinician-rated instrument for measuring anxiety in youth with ASDs who participate in clinical trials. We propose a mixed method approach in line with the FDA monograph: Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims (www.Fda.Gov/Cder /Guidance). In Yr 1, focus groups with parents will explore the manifestations of anxiety in children with ASDs. This information will be used to refine the CASI Anxiety scale (DSM-IV-based parent-rating) and modify the clinician-rated Pediatric Anxiety Rating Scale (PARS). Yr 2 will collect data on the revised CASI Anx scale (20-25 items) in 900 children with ASD ages 5 to 17 years on a secure web site. We will examine the distribution, internal consistency, factor structure and item analysis of this parent-rated scale. Test-retest reliability of the scale will be evaluated in a subsample of online respondents and a sample of subjects assessed in person. Validity of the CASI Anx scale will be evaluated by contrasting the correlations with another parent-rated measure of anxiety (convergent validity) and with measures of repetitive behavior, social disability and irritability (divergent validity). The revised PARS will be collected via in person assessments of 90 subjects to evaluate reliability (inter-rater, internal consistency) and validity in Yr 3. In Yrs 34, a high anxiety subgroup (above threshold on the CASI Anx scale) will be compared to controls (ASD with low anxiety) on physiological measures of heart rate [HR], heart rate variability [HRV] and electrodermal activity [EDA]). HR, HRV and EDA will be measured at rest and under mildly anxiety provoking conditions. Results from this exploratory investigation may identify read outs for early testing of compounds for anxiety in ASDs. The project has four deliverables: focus group results (Yr 2); a reliable and valid parent-rated anxiety outcome measure (Yr 3); a reliable and valid clinician-rated anxiety measure (Yr 4); preliminary HRV and EDA findings (soon after the grant period).

描述（由申请人提供）：这个为期四年的多地点项目将在未来针对患有自闭症谱系障碍（ASD）的青少年的临床试验中推进焦虑的结果测量。计划公告 (PAR-11-045) 宣称，缺乏发育障碍人群的结果测量是发育障碍人群药物研究的主要障碍。损害焦虑在患有 ASD 的青少年中很常见，也是一个看似合理的治疗目标，但研究很少（White 等，2009；van Steensel 等，2011；King 等人，2009）。对于典型发育中的青少年的焦虑，有一些广为接受的结果测量（RUPP Anxiety Group，2001；Walkup et al.，2008）。鉴于自闭症谱系障碍者的语言和认知缺陷，这些措施不加修改地不适合患有自闭症谱系障碍的青少年。消费者团体也注意到需要对患有自闭症谱系障碍的青少年的焦虑进行结果测量（www.autismspeaks.org）。我们组建了一支由研究人员和顾问组成的优秀团队，开发一种家长评级和临床医生评级的工具，用于测量参加临床试验的自闭症谱系障碍青少年的焦虑程度。我们提出了一种符合 FDA 专着的混合方法：患者报告的结果测量：用于医疗产品开发以支持标签声明 (www.Fda.Gov/Cder/Guidance)。在第一年，与家长一起的焦点小组将探讨自闭症谱系障碍儿童的焦虑表现。该信息将用于完善 CASI 焦虑量表（基于 DSM-IV 的家长评级）并修改临床医生评级的儿科焦虑评级量表 (PARS)。第二年将在安全网站上收集 900 名 5 至 17 岁 ASD 儿童的修订版 CASI Anx 量表（20-25 项）数据。我们将检验这个家长评分量表的分布、内部一致性、因素结构和项目分析。量表的重测信度将在在线子样本中进行评估 受访者和亲自评估的受试者样本。 CASI Anx 量表的有效性将通过与另一种家长评价的焦虑测量（趋同效度）以及重复行为、社交障碍和易怒测量（发散效度）的相关性进行对比来评估。修订后的 PARS 将通过对 90 名受试者进行个人评估来收集，以评估第 3 年的可靠性（评估者间、内部一致性）和有效性。在第 34 年，将在心率 [HR]、心率变异性 [HRV] 和皮肤电活动 [EDA] 的生理测量方面，将高度焦虑亚组（高于 CASI Anx 量表的阈值）与对照组（具有低焦虑的 ASD）进行比较。 HR、HRV 和 EDA 将在休息和轻度焦虑条件下进行测量。这项探索性调查的结果可能会确定用于早期测试 ASD 焦虑化合物的读数。该项目有四个可交付成果： 焦点小组结果（第二年）；可靠且有效的家长评定的焦虑结果测量（三年级）；可靠且有效的临床医生评定的焦虑测量（四年级）；初步 HRV 和 EDA 结果（资助期结束后不久）。