The Clinical Global Impression-Severity (CGI-S) and CGI-Improvement (CGI-I) scales are widely accepted tools that measure overall disease severity and change, synthesizing the clinician’s impression of the global state of an individual. Frequently employed in clinical trials for neuropsychiatric disorders, the CGI scales are typically used in conjunction with disease-specific rating scales. When no disease-specific rating scale is available, the CGI scales can be adapted to reflect the specific symptom domains that are relevant to the disorder. Angelman syndrome (AS) is a rare, clinically heterogeneous condition for which there is no disease-specific rating scale. This paper describes efforts to develop standardized, adapted CGI scales specific to AS for use in clinical trials. In order to develop adapted CGI scales specific to AS, we (1) reviewed literature and interviewed caregivers and clinicians to determine the most impactful symptoms, (2) engaged expert panels to define and operationalize the symptom domains identified, (3) developed detailed rating anchors for each domain and for global severity and improvement ratings, (4) reviewed the anchors with expert clinicians and established minimally clinically meaningful change for each symptom domain, and (5) generated mock patient vignettes to test the reliability of the resulting scales and to standardize rater training. This systematic approach to developing, validating, and training raters on a standardized, adapted CGI scale specifically for AS is described herein. The resulting CGI-S/I-AS scales capture six critical domains (behavior, gross and fine motor function, expressive and receptive communication, and sleep) defined by caregivers and expert clinicians as the most challenging for patients with AS and their families. Rigorous training and careful calibration for clinicians will allow the CGI-S/-I-AS scales to be reliable in the context of randomized controlled trials. The CGI-S/-I-AS scales are being utilized in a Phase 3 trial of gaboxadol for the treatment of AS.

中文翻译：

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开发适用于 Angelman 综合征的适应临床总体印象量表

临床总体印象-严重程度 (CGI-S) 和 CGI​​-改善 (CGI-I) 量表是广泛接受的工具，用于测量整体疾病严重程度和变化，综合临床医生对个体整体状态的印象。CGI 量表经常用于神经精神疾病的临床试验，通常与特定疾病的评级量表结合使用。当没有疾病特定的评分量表可用时，可以调整 CGI 量表以反映与疾病相关的特定症状域。Angelman 综合征 (AS) 是一种罕见的、临床上异质性的疾病，没有针对特定疾病的评分量表。本文描述了为用于临床试验而开发特定于 AS 的标准化、适应性 CGI 量表的努力。为了开发特定于 AS 的自适应 CGI 比例，我们 (1) 回顾了文献并采访了护理人员和临床医生，以确定最具影响力的症状，(2) 聘请专家小组来定义和实施所确定的症状领域，(3) 为每个领域以及全球严重程度和改善评级制定详细的评级锚, (4) 与专家临床医生一起审查锚点，并为每个症状领域建立具有最小临床意义的变化，以及 (5) 生成模拟患者小插曲以测试所得量表的可靠性并标准化评估员培训。本文描述了这种在标准化的、经过调整的 CGI 量表上专门针对 AS 开发、验​​证和培训评分者的系统方法。由此产生的 CGI-S/I-AS 量表涵盖了六个关键领域（行为、粗大和精细运动功能、表达和接受交流、和睡眠）被护理人员和专家临床医生定义为对 AS 患者及其家人最具挑战性。对临床医生的严格培训和仔细校准将使 CGI-S/-I-AS 量表在随机对照试验的背景下可靠。CGI-S/-I-AS 量表正用于加波沙朵治疗 AS 的 3 期试验。