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

基本信息

批准号：
10186591
负责人：
ANJALI SADHWANI
金额：
$ 9.01万
依托单位：
RESEARCH TRIANGLE INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10186591
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

项目摘要

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.

项目摘要/摘要 Angelman综合征（AS）是一种罕见的神经遗传疾病，导致许多临床特征，包括严重的发育延迟和功能极为有限的功能。治疗性在过去的几年中，发展工作大大增加，有七个目前正在进行或准备1期试验的制药公司。结果，有提高核心临床结果指标的效用的迫切需要在AS的将来的临床试验中有效部署。这项研究的总体目标是使用现有关于两种核心工具的800多个管理的数据，即婴儿的贝利尺度发展和Vineland自适应行为量表，以建立有意义的变化这两个措施的阈值。为了实现这一目标，我们将计算对于每个度量（a）基于分布的最小临床重要差异（MCID），（b）基于锚的MCID。基于锚的MCID与美国食品和药物很好地吻合政府（FDA）建立“有意义的内部变更”的指南（请参阅 https://www.fda.gov/media/132505/download），甚至FDA都认识到经验数据对于将临床结果评估的变化进行情境化而言是必要的。分布 - 基于的MCID方法将在基于锚的方法上提供此“现实检查”，以确保变化的阈值在统计学上具有重要意义，并且在临床上有意义。