PROMIS-guided development and validation of a dimensional observer-report measure of positive and negative features of ASD

PROMIS 引导的 ASD 积极和消极特征的维度观察者报告测量的开发和验证

• 批准号: 10412052
• 负责人: Jennifer Foss-Feig
• 金额: $ 80.7万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-06 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10412052
• 关键词: 11 year old; Address; Age; Assessment tool; Behavior; Biological; Biological Response Modifier Therapy; Brain; Calibration; Caregivers; Categories; Characteristics; Child; Clinical; Clinical Services; Clinical Trials; Communities; Data; Detection; Development; Diagnosis; Diagnostic; Dimensions; Discrimination; Echolalia; Equipment and supply inventories; Etiology; Evaluation; Factor Analysis; Failure; Funding; Genetic; Genetic study; Genotype; Goals; Gold; Heterogeneity; Individual; Information Systems; Intervention; Intervention Studies; Interview; Investigational Therapies; Investments; Language; Link; Measurable; Measurement; Measures; Mental disorders; Methods; Motor; Neurobiology; Neurodevelopmental Disorder; Outcome Measure; Outcome Study; Parents; Patient Outcomes Assessments; Phenotype; Play; Procedures; Provider; Psychometrics; Reporting; Research; Schizophrenia; Severities; Specificity; Standardization; Stratification; Structure; Symptoms; Testing; Time; United States National Institutes of Health; Validation; Work; associated symptom; autism community; autism spectrum disorder; autistic children; biological sex; brain behavior; clinical practice; comorbidity; deviant; effective therapy; individuals with autism spectrum disorder; innovation; instrument; joint attention; neuroimaging; neuromechanism; novel; personalized medicine; response; social; success; symptomatology; targeted treatment; theories; therapeutically effective; therapy development; tool; treatment effect; treatment response

PROJECT SUMMARY Marked heterogeneity among individuals with autism spectrum disorder (ASD) is a significant problem facing the autism community. Heterogeneity makes it difficult to identify core biological disruptions. It also hampers the development and validation of targeted and consistently effective therapeutics. In particular, the lack of precise, psychometrically robust, change sensitive outcome measures for core symptomatology represents a key barrier for clinical trials and for detecting mechanisms underlying manifest symptoms. This project proposes to develop and validate an innovative new observer report measure for ASD that attempts to capture heterogeneity in core symptoms along positive and negative dimensions, akin to those that have been successful in quantifying heterogeneity and facilitating key biological and therapeutic discoveries in schizophrenia. Using state-of-the-art procedures put forth by the NIH Patient-Reported Outcome Measurement Information System (PROMIS®) initiative, this project will develop, calibrate, and validate a new tool - the Positive and Negative Inventory for ASD (PNI) - for assessing core ASD symptoms with unprecedented precision of symptom description and discrimination, along conceptually novel dimensions. First, our preliminary item pool will be refined with key stakeholder input from caregivers and national experts. Next, caregivers of 1,000 3-11 year old children with ASD and 400 typically developing and non-ASD clinical controls will complete the PNI. A combination of classical item analysis and factor analysis will be used to identify the best-performing items, which will then be calibrated using Item Response Theory (IRT) and co-calibrated with legacy measures to demonstrate superiority of PNI item and scale function. Baseline inter-rater and 6-week test-retest reliability, 24-week change sensitivity, and sensitivity in the context of an upcoming clinical trial all will be assessed, both convergent and divergent validity will be tested, and a short form will be developed. Preliminary data demonstrate both the utility of parsing individual behaviors, currently subsumed within larger categories, into positive and negative dimensions and the success of PROMIS® methods and IRT for developing sensitive tools for ASD. We anticipate that this innovative, scientifically rigorous study will result in a calibrated and validated assessment tool for ASD with an empirically-supported factor structure and items that are both precise in their descriptive capturing of symptoms and sensitive to variability in the latent dimensions, within and across children. We also expect that the PNI will show excellent reliability and change sensitivity, offering a promising outcome measure for use in ASD clinical trials. Long term, we expect this research to have significant clinical benefits, including: 1) offering a new tool for assessing experimental therapeutics, 2) providing a new framework within which to test brain mechanisms and genetic contributions to specific feature manifestations, and 3) contributing to more nuanced application of targeted treatment in community clinical practice by offering a rapid, innovative, precise, and sensitive way to quantify heterogeneity in ASD.

项目摘要 自闭症谱系障碍（ASD）中的明显异质性是一个重大问题 自闭症社区。异质性使难以识别核心生物学破坏。它也妨碍了 有针对性且一致的有效疗法的开发和验证。特别是缺乏 精确，心理稳健，改变核心症状的敏感结果指标代表 临床试验和检测明显符号的机制的关键障碍。这个项目 提出开发和验证创新的新观察者报告ASD试图捕获的新观察者报告措施 沿正尺寸和负尺寸的核心症状的异质性，类似于那些 成功量化异质性并支持关键的生物学和治疗发现 精神分裂症。使用NIH患者报告的结果测量的最新程序 信息系统（Promis®）计划，该项目将开发，校准和验证一个新工具 - ASD（PNI）的积极和负面清单 - 用于评估前所未有的核心ASD症状 症状描述和歧视的精度，沿概念上的新维度。首先，我们的 初步项目池将通过照顾者和国家专家的主要利益相关者投入来完善。下一个， 1,000名3-11岁儿童ASD和400名通常开发和非ASD临床对照的护理人员 将完成PNI。经典项目分析和因子分析的组合将用于确定 最佳表现的项目将使用项目响应理论（IRT）进行校准，并与 遗留措施以证明PNI项目和规模功能的优势。基线评估者和6周 在即将进行的临床试验的背景下，测试可靠性，24周的变化灵敏度和灵敏度 将评估，将测试收敛性和发散性有效性，并将开发出短的形式。 初步数据证明了解析个体行为的实用性，目前属于较大的行为 类别，分类为正和负尺寸以及Promis®方法的成功和IRT的成功 为ASD开发敏感工具。我们预计这项创新，科学严格的研究将导致 具有经验支持的因子结构和项目的ASD校准和验证的评估工具 它们在描述性捕获症状的描述性捕获方面都很精确，并且对潜在维度的可变性敏感， 在儿童内部和跨儿童。我们还希望PNI表现出极好的可靠性和改变灵敏度， 为ASD临床试验提供了有希望的结果指标。长期，我们希望这项研究能够 具有重大的临床益处，包括：1）提供一种评估实验疗法的新工具，2） 提供一个新的框架，以测试大脑机制和对特定特征的遗传贡献 表现和3）有助于在社区临床中更细微地应用有针对性的治疗 通过提供快速，创新，精确和敏感的方法来量化ASD中的异质性。