Development of an adapted Clinical Global Impression scale for use in Angelman syndrome

Abstract

Background 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. Methods 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. Results 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. Conclusions 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.

Understanding the impact of tuberous sclerosis complex: development and validation of the TSC-PROM

“…This is important for evaluating novel treatments such as anti-seizure medication, mTOR inhibitors, cannabidiol treatments, and eventually more (expensive) targeted therapies such as gene or RNA modification [ 2 , 71 ]. Although a TAND-specific outcome measure is under development [ 72 ], the assessment of all relevant health domains in individuals with TSC has been hampered by the lack of a TSC-specific measure [ 9 ], comparable to several other rare diseases for which disease-specific outcome measures have eventually been developed [ 28 , 73 – 76 ].…”

Etomidate versus Propofol for Electroconvulsive Therapy in Patients with Major Depressive Disorders in Terms of Clinical Responses to Treatment: A Retrospective Analysis

“…It is a reliable tool for the evaluation of psychiatric disorder [10]. There are two types of CGI: CGI-severity (CGI-S) and CGI-improvement (CGI-I) [11]. CGI-S assesses the current severity of illness, while CGI-I evaluates the degree of change before and after treatment [12].…”

Uso de cannabidiol para el control de síntomas refractarios en síndromes convulsivos y enfermedades neurodegenerativas

“…Miller et al identificaron que el 68 % de pacientes que obtuvieron la terapia adicional con otro fármaco de CBD presentaron una mejoría según la escala Caregiver Global Impression of Change (CGIC) 34 . Esta es una herramienta que fue diseñada en 1976 para evaluar la severidad, mejoría global y respuesta terapéutica de una enfermedad, la cual es una escala tipo Likert implementada por el cuidador del paciente y se utiliza principalmente en trastornos psiquiátricos, enfermedades neurodegenerativas y trastornos convulsivos 35 . La CGIC ha sido el principal instrumento en múltiples ensayos clínicos sobre el uso de Cannabidiol en pacientes con síndromes convulsivos para evaluar la reducción en la frecuencia y duración de las convulsiones identificadas por el cuidador 36 .…”