Authors :
Presenting Author: Jacqueline Gofshteyn, MD – Encoded Therapeutics - South San Francisco, CA
Clara Juandó-Prats, MScN, PhD – Applied Health Research Centre, Li Ka Shing Knowledge Institute, Unity Health Toronto; M. Scott Perry, MD – Cook Children’s Medical Center; Ingrid Scheffer, AO, FAA, FAHMS – University of Melbourne, Austin Health; Joseph Sullivan, MD – University of California at San Francisco; Susana Boronat, MD, PhD – Hospital de la Santa Creu i Sant Pau; James Wheless, MD – Le Bonheur Children's Hospital; Andreas Brunklaus, MD – Royal Hospital for Children; Linda Laux, MD – Ann & Robert H. Lurie Children's Hospital of Chicago; Anup Patel, MD – Nationwide Children’s Hospital; Colin Roberts, MD – Doernbecher Children’s Hospital; Dennis Dlugos, MD, MSCE – Children’s Hospital of Philadelphia; Deborah Holder, MD – Children's Hospital Los Angeles; Kelly Knupp, MD – Children’s Hospital Colorado; Matt Lallas, MD – Nicklaus Children’s Hospital; Steven Phillips, MD – Multicare Health System; Eric Segal, MD – Northeast Regional Epilepsy Group; Dennis Lal, PhD – Cleveland Clinic Lerner Research Institute; Elaine Wirrell, MD – Mayo Clinic; Sameer Zuberi, MD – Royal Hospital for Children; Sarah Christensen, - – Encoded Therapeutics; Kathryn Hodwitz, MSc – Applied Health Research Centre, Li Ka Shing Knowledge Institute, Unity Health Toronto; Norman Huang, PhD – Encoded Therapeutics; Emma James, PhD – Encoded Therapeutics; Maria Candida Vila, PharmD, PhD – Encoded Therapeutics; Salvador Rico, MD, PhD – Encoded Therapeutics
Rationale:
Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy characterized by refractory seizures and global developmental delay. ENVISION, a prospective natural history study, explored factors influencing Health-Related Quality of Life (HRQoL), including assessing the appropriateness of selected HRQoL measurement tools for young DS children and their families.
Methods:
The full spectrum of disease manifestations in children aged six months to five years with SCN1A+ DS was evaluated every three months. We utilized a mixed methods approach, quantifying HRQoL in children using the PedsQL (parent proxy version) and in caregivers via the SF-12 and EQ-5D-5L. Parents who consented were interviewed in-depth throughout the stud, and data was analyzed through a narrative, reflexive thematic process.
Results:
Fifty-eight children with SCN1A+ DS enrolled across sixteen sites worldwide (median age 2.3 years). The PedsQL detected a yearly decrease of 2.3 points in total Quality of Life (QoL) in children with DS as they aged, with similar impacts on psychosocial and physical health domains. The SF-12 indicated an increase in caregiver mental health (T-score increased by 1.5 points per year; normative mean=50; SD=10) while slightly declining physical health remained within the normative range (T-score decrease of 1.9 points/year; normative mean=50; SD=10). The EQ-5D-5L scores did not show a marked decline as DS children aged, with caregivers of children <2 years and >3.5 years scoring an average of 77.3 (SD 17.3) and 73.6 (SD 11.3) at enrollment respectively. Twenty-eight parents of participants consented to in-depth, qualitative interviews, which illustrated that caregivers’ HRQoL is particularly challenging and negatively impacted during the early years and, as the child grows, the physical burden of caregiving increases. While, over time, identification of specialists, optimization of symptom management, and social, emotional, and economic support may ease the burden, difficulties related to obtaining a diagnosis, navigating healthcare systems, advocating for their child, and adjusting individual and familial expectations burden all families.
Conclusions:
Parent-reported, quantitative measures show a modest decline in HRQoL in children with DS and relative stability in caregivers' HRQoL with a minor decline in physical health. However, caregivers may adapt to the challenges of caring for a child with DS, possibly underreporting or normalizing certain aspects as part of their regular experience, and qualitative interviews revealed a complex reality. Difficulties in securing a diagnosis and treatment, alongside healthcare inequities, substantially affect caregivers' professional lives, economic situations, and social-mental wellbeing. This mixed methods approach offers insights into the nuanced complexities of assessing HRQoL in DS, suggesting existing quantitative tools may not fully capture the true disease burden in this population.
Funding: This study was funded by Encoded Therapeutics.