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: 10653177
• 负责人: Jennifer Foss-Feig
• 金额: $ 79.49万
• 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/10653177
• 关键词: 11 year old; Address; Age; Assessment tool; Behavior; Biological; 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; Heterogeneity; Individual; Information Systems; Intervention; Intervention Studies; Interview; Investigational Therapies; Investments; Language; Link; Measurable; 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; Therapeutic; 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; verbal

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.

项目概要 自闭症谱系障碍 (ASD) 患者之间明显的异质性是面临的一个重大问题 自闭症群体的异质性使得识别核心生物破坏变得困难。 针对性和持续有效的治疗方法的开发和验证尤其缺乏。 核心症状学的精确、心理测量稳健、变化敏感的结果测量代表了 该项目是临床试验和检测明显症状机制的关键障碍。 建议开发并验证一种针对自闭症谱系障碍（ASD）的创新观察员报告措施，试图捕捉 核心症状在积极和消极维度上的异质性，类似于那些 成功量化异质性并促进关键的生物学和治疗发现 使用 NIH 患者报告的结果测量提出的最先进的程序。 信息系统 (PROMIS®) 计划，该项目将开发、校准和验证一种新工具 - ASD 阳性和阴性清单 (PNI) - 用于以前所未有的方式评估 ASD 核心症状 症状描述和辨别的准确性，以及概念上新颖的维度。 接下来，将根据主要利益相关者和国家专家的意见完善初步项目库。 1,000 名 3-11 岁患有自闭症谱系障碍 (ASD) 儿童和 400 名典型发育和非自闭症谱系障碍 (ASD) 临床对照儿童的看护者 将使用经典项目分析和因子分析的组合来完成 PNI。 表现最好的项目，然后使用项目响应理论（IRT）进行校准，并与 证明 PNI 项目和量表功能的基线评估者和 6 周的优越性的传统措施。 重测可靠性、24 周变化敏感性以及即将进行的临床试验的敏感性 将进行评估，测试收敛和发散的有效性，并制定一个简短的表格。 初步数据证明了解析个体行为的实用性，目前包含在更大的范围内 类别，分为积极和消极维度以及 PROMIS® 方法和 IRT 的成功 我们预计这项创新的、科学严谨的研究将产生一个针对自闭症谱系障碍（ASD）的敏感工具。 经过校准和验证的 ASD 评估工具，具有经验支持的因素结构和项目， 既能精确地描述症状，又能对潜在维度的变化敏感， 我们还期望 PNI 将表现出出色的可靠性和变化敏感性， 从长远来看，我们期望这项研究能够为自闭症谱系障碍（ASD）临床试验提供有希望的结果测量。 具有显着的临床益处，包括：1）提供评估实验疗法的新工具，2） 提供一个新的框架来测试大脑机制和遗传对特定特征的贡献 表现，3）有助于靶向治疗在社区临床中更细致的应用 通过提供快速、创新、精确和灵敏的方法来量化自闭症谱系障碍的异质性，从而促进实践。