Tools measure Angelman severity from clinician, caregiver perspective
The tools can help measure a treatment's impact in clinical trials
Two new standardized tools to measure the severity of Angelman syndrome (AS) in children — one based on clinician assessments and another on caregiver reports — have been developed and are in use in clinical trials to measure the disease’s severity and evaluate the impact of potential treatments.
These tools “both specifically and holistically assess clinician and caregiver perspectives and can be used to provide valuable insight into the severity, impact, and meaningful change in individuals with AS,” wrote the researchers, who described the tools’ development in “Developing Angelman syndrome-specific clinician-reported and caregiver-reported measures to support holistic, patient-centered drug development,” in the Orphanet Journal of Rare Diseases.
When researchers design clinical trials to test experimental therapies, one of the most important considerations is how to measure a treatment’s impact. That’s why it’s necessary to have tools that can accurately assess a disease’s severity, so researchers can assess whether the treatment is having an effect.
“At the time of this study, no AS-specific [clinical outcomes assessments] that holistically reviewed the status of patients with AS were publicly available,” the researchers wrote. “Hence, there was a need to develop measures that capture the complexity and heterogeneity of AS symptom burden from the clinician and the caregiver perspectives.”
The measures — Symptoms of AS-Clinician Global Impression (SAS-CGI) and the Caregiver-reported AS Scale (CASS) — were respectively designed for clinicians or caregivers, “given that clinician reports of a condition can differ compared with caregivers,” they said, adding having both assessments will offer “a fuller picture of treatment outcomes.”
Developing the tools to measure Angelman severity
To create the tools, the researchers interviewed doctors with expertise in treating Angelman, patient advocates, and caregivers of children with the disease.
The tools covered eight general domains to assess the various ways in which the disease can have an impact — seizures, sleep issues, difficult behaviors, problems with communication, poor fine motor skills, poor gross motor skills, impaired cognition, and limited ability to care for oneself. Gross and fine motor skills were included separately since they can affect different aspects of physical ability. Gross motor skills are for large movements like crawling, whereas fine motor skills are required for more delicate acts like picking something up.
“These domains were incorporated into the measures to ensure that the most challenging aspects of AS were captured, which is in line with the [U.S. Food and Drug Administration] guidance for patient-centered drug development,” the researchers wrote.
Both tools include a single question for each domain, as well as questions about the overall severity of Angelman and observed changes over time.
The clinician-focused tool focuses on the severity of symptoms from a clinical perspective, whereas the caregiver tool asks about their impact on the child and their family. This makes them complementary tools that “could be incorporated into clinical trials to assess changes from both the clinician and caregiver perspective in response to targeted AS therapies,” the researchers wrote.
The tools are already being used in clinical studies. They’re among the main measures being tracked in FAST UK (NCT05100810), a natural history study of how Angelman progresses in the absence of treatment. The measures were also included in early trials of rugonersen (RO7248824), an experimental therapy recently discontinued as a result of lackluster results.
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