Abstracts

Rationale: Existing clinical tools that measure non-seizure outcomes lack the range and

granularity needed to capture skills in those with developmental and epileptic encephalopathies (DEEs) who also have a severe to profound range of intellectual disability. This effectively excludes those with severe impairments from clinical trials, impeding the ability of sponsors to evaluate disease-modifying therapies (DMTs). The Inchstone Project is an interdisciplinary, patient advocacy group-led (PAG) collaboration working to develop a validated assessment battery for this group. The goal is to support trials of DMTs that are inclusive of even the most severely affected individuals with DEEs by providing sufficiently sensitive measurement tools to demonstrate therapeutic efficacy across a range of domains most important to families.


Methods: An online survey was disseminated to caregivers of individuals with severe to profound functional impairments through PAGs affiliated with DEE-P Connections. Caregivers completed surveys about priorities for treatment and impacts of impairments, functional skills (i.e., development, awareness and responsivity to the environment, vision) and quality of life.

Results: The sample included 268 caregivers who completed the surveys about their child (mean age=10 years; 56% female). Seventy-five percent reported seizures, 37% autism, and 33% cortical visual impairment (CVI). Seventy-nine percent of parents reported expressive communication as a top priority for change, 38% reported gross motor skills, and 27% listed receptive communication. The average developmental quotient (DQ) for this sample ranged from 9.7 (communication) to 14.4 (cognition). DQs for the profoundly impaired are on average 18 points lower than those with fewer, less-severe impairments. The awareness measure yielded good range and no ceiling or floor effects. Awareness scores were positively correlated with the cognition scale on the developmental measure (r = .683, p = 2.2e-16), but provided more range and variability for those with a mental age below 12 months. Initial analysis of the novel vision measure shows evidence of validity (e.g., more vision impairment with greater functional impairment; discriminates those with and without diagnosed CVI). Quality of life responses also indicate evidence of validity, range, and variability. Qualitative analysis of 810 parent-reported priorities for meaningful changes showed that while there is consistency in priorities across all levels of impairment, the increments of meaningful change vary.

Conclusions: Findings from this caregiver survey offer promising insights towards building the knowledge base about what domains are most meaningful to families and the utility of extant measures of these domains in this population, which is critical to the development of fit-for-purpose measures. Focus group discussions and in-person clinical assessments are underway to validate and deepen our understanding of the current utility and necessary adaptations of the surveys examined in this study for this patient group.




Funding: The work is funded by The Inchstone Project, an arm of DEE-P Connections.