Determining minimal clinically important differences for neurodevelopmental outcome measures in Angelman syndrome

确定天使综合征神经发育结果测量的最小临床重要差异

• 批准号: 10396549
• 负责人: ANJALI SADHWANI
• 金额: $ 9.05万
• 依托单位: RESEARCH TRIANGLE INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10396549
• 关键词: Activities of Daily Living; Adaptive Behaviors; Angelman Syndrome; Antisense Oligonucleotide Therapy; Antisense Oligonucleotides; Ataxia; Benchmarking; Biological Response Modifier Therapy; COVID-19 pandemic; Caregivers; Child; Chromosome 15; Chromosome Deletion; Clinical; Clinical Trials; Collaborations; Communication; Communities; Consensus; Data; Development; Developmental Delay Disorders; Disease; Ensure; Functional disorder; Future; General Population; Genetic Predisposition to Disease; Goals; Impairment; Individual; Infant; Infant Development; Inherited; Intellectual functioning disability; Language; Measures; Methodology; Methods; Modeling; Motor; Neurodevelopmental Disorder; Neurons; Other Genetics; Outcome Measure; Patients; Pharmacologic Substance; Phase I Clinical Trials; Phase I/II Trial; Prevalence; Psychometrics; Research Personnel; Seizures; Sleep disturbances; Speech; Therapeutic; Time; Toddler; UBE3A gene; United States; United States Food and Drug Administration; Work; base; clinical outcome assessment; clinical outcome measures; clinically significant; cognitive function; gene therapy; improved; instrument; interest; neurodevelopment; neurogenetics; phase I trial; social; therapeutic development; therapeutic target; trait

Project Summary/Abstract Angelman syndrome (AS) is a rare neurogenetic condition that results in a host of clinical traits, including severe developmental delays and extremely limited functional abilities. Therapeutic development efforts have increased substantially in the last several years, with seven pharmaceutical companies currently conducting or preparing Phase 1 trials. As a result, there is a critical need to improve the utility of core clinical outcome measures so that they can be deployed effectively in future clinical trials in AS. The overall goal of this study is to use existing data on over 800 administrations of two core instruments, the Bayley Scales of Infant Development and the Vineland Adaptive Behavior Scales, to establish meaningful change thresholds for these two measures for individuals with AS. To achieve this goal, we will calculate for each measure (a) distribution-based minimal clinically important difference (MCID), and (b) anchor-based MCID. The anchor-based MCID aligns well with the U.S. Food and Drug Administration’s (FDA’s) guidance on establishing “meaningful within-patient change” (see https://www.fda.gov/media/132505/download), yet even the FDA recognizes that empirical data are necessary to contextualize changes on Clinical Outcome Assessments. The distribution- based MCID approach will provide this “reality check” on the anchor-based approach, ensuring that thresholds for change are both statistically significant and clinically meaningful.

项目总结/摘要 Angelman综合征（AS）是一种罕见的神经遗传性疾病，导致许多临床特征， 包括严重的发育迟缓和极其有限的功能能力。治疗 在过去几年里，发展努力大幅度增加， 目前正在进行或准备1期试验的制药公司。结果是 迫切需要提高核心临床结局指标的实用性， 在未来的AS临床试验中有效部署。本研究的总体目标是利用现有的 两个核心工具的800多个管理数据，贝利婴儿量表 开发和葡萄园适应行为量表，以建立有意义的变化 这两个指标的阈值为个人与AS。为了实现这一目标，我们将计算 对于每个测量，（a）基于分布的最小临床重要差异（MCID），和（B） 基于锚的MCID基于锚点的MCID与美国食品和药物管理局（FDA） 美国食品药品监督管理局（FDA）关于确定“有意义的患者内变化”的指南（见 https：//www.fda.gov/media/132505/download），但即使是FDA也认识到， 有必要将临床结局评估的变化置于背景中。分配- 基于MCID的方法将对基于锚点的方法进行“现实检查”，确保 变化的阈值具有统计学意义和临床意义。