A Conceptual Model of Angelman Syndrome and Review of Relevant Clinical Outcomes Assessments (COAs)

Grieco, Joseph C.; Romero, Beverly; Flood, Emuella; Cabo, Raquel; Visootsak, Jeannie

doi:10.1007/s40271-018-0323-7

Cited by 24 publications

(62 citation statements)

References 25 publications

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“…In this instance, the field is fortunate that another conceptual model of AS was recently published by Grieco et al [29]. Both studies drew from a literature review, followed by clinician and caregiver interviews, but differ in approach.…”

Section: Discussionmentioning

confidence: 99%

Measuring What Matters to Individuals with Angelman Syndrome and Their Families: Development of a Patient-Centered Disease Concept Model

Willgoss

Cassater

Connor

et al. 2020

Child Psychiatry Hum Dev

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Angelman syndrome (AS) is a complex, heterogeneous, and life-long neurodevelopmental disorder. Despite the considerable impact on individuals and caregivers, no disease-modifying treatments are available. To support holistic clinical management and the development of AS-specific outcome measures for clinical studies, we conducted primary and secondary research identifying the impact of symptoms on individuals with AS and their unmet need. This qualitative research adopted a rigorous step-wise approach, aggregating information from published literature, then evaluating it via disease concept elicitation interviews with clinical experts and caregivers. We found that the AS-defining concepts most relevant for treatment included: impaired expressive communication, seizures, maladaptive behavior, cognitive impairment, motor function difficulties, sleep disturbance, and limited self-care abilities. We highlight the relevance of age in experiencing these key AS concepts, and the difference between the perceptions of clinicians and caregivers towards the syndrome. Finally, we outline the impact of AS on individuals, caregivers, and families.

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Section: Discussionmentioning

confidence: 99%

Measuring What Matters to Individuals with Angelman Syndrome and Their Families: Development of a Patient-Centered Disease Concept Model

Willgoss

Cassater

Connor

et al. 2020

Child Psychiatry Hum Dev

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“…This cohort represents approximately 75% of all children with AS in the Netherlands, which limits referral bias. Most issues regarding health and development (epilepsy, sleep, gastrointestinal problems, mobility, cognition, communication, and behavior) that are addressed in our clinical follow‐up were recently stated as being very important concerns for parents of children with AS (Grieco et al, ; Wheeler et al, ) and will be targeted as relevant clinical outcomes in future trials.…”

Section: Discussionmentioning

confidence: 99%

An overview of health issues and development in a large clinical cohort of children with Angelman syndrome

Heus

Mous

Hooven‐Radstaake

et al. 2019

American J of Med Genetics Pt A

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This study presents a broad overview of health issues and psychomotor development of 100 children with Angelman syndrome (AS), seen at the ENCORE Expertise Center for AS in Rotterdam, the Netherlands. We aimed to further delineate the phenotype of AS, to evaluate the association of the phenotype with genotype and other determinants such as epilepsy and to get insight in possible targets for intervention. We confirmed the presence of a more severe phenotype in the 15q11.2-q13 deletion subtype. Novel findings were an association of (early onset of) epilepsy with a negative effect on development, a high occurrence of nonconvulsive status epilepticus, a high rate of crouch gait in the older children with risk of deterioration of mobility, a relatively low occurrence of microcephaly, a higher mean weight for height in all genetic subtypes with a significant higher mean in the nondeletion children, and a high occurrence of hyperphagia across all genetic subtypes. Natural history data are needed to design future trials. With this large clinical cohort with structured prospective and multidisciplinary follow-up, we provide unbiased data on AS to support further intervention studies to optimize outcome and quality of life of children with AS and their family. K E Y W O R D S development, epilepsy, genotype-phenotype, growth, UBE3A

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“…Based on the lessons learned from the Phase 2 trial, we undertook a more elaborate approach to improve the reliability and validity of the adapted scale for use in the Phase 3 trial of gaboxadol for AS [21][22][23]. Our own early conceptual model development work [24], broadly confirmed by that of Willgoss et al [25], formed the conceptual basis on which the original nine domains were reduced to six broad domain categories and detailed rating anchors were developed.…”

Section: Angelman Syndromementioning

confidence: 99%

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

Kolevzon

Ventola

Keary

et al. 2021

J Neurodevelop Disord

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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.

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A Conceptual Model of Angelman Syndrome and Review of Relevant Clinical Outcomes Assessments (COAs)

Cited by 24 publications

References 25 publications

Measuring What Matters to Individuals with Angelman Syndrome and Their Families: Development of a Patient-Centered Disease Concept Model

Measuring What Matters to Individuals with Angelman Syndrome and Their Families: Development of a Patient-Centered Disease Concept Model

An overview of health issues and development in a large clinical cohort of children with Angelman syndrome

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

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