DRAVET ENGAGE. Parent caregivers of children with Dravet syndrome: Perspectives, needs, and opportunities for clinical research

Abstract

Dravet syndrome (DS) is an intractable developmental and epileptic encephalopathy significantly impacting affected children and their families. A novel, one-time, adeno-associated virus (AAV)-mediated gene regulation therapy was designed to treat the underlying cause of DS, potentially improving the full spectrum of DS manifestations. To ensure the first-in-human clinical trial addresses meaningful outcomes for patients and families, we examined their perspectives, priorities, goals, and desired outcomes in the design phase through a mixed methods approach (quantitative and qualitative). We conducted a non-identifiable parent caregiver survey, shared through a patient advocacy organization (n = 36 parents; children age 6 years). Parents were also engaged via three group discussions (n = 10; children age 2-20 years) and optional follow-up in-depth individual interviews (n = 6). Qualitative data analysis followed an inductive interpretive process, and qualitative researchers conducted a thematic analysis with a narrative approach. Survey results revealed most children (94%) were diagnosed by age 1, with onset of seizures at mean age 6.2 months and other DS manifestations before 2 years. The most desired disease aspects to address with potential new disease-modifying therapies were severe seizures (ranked by 92% of caregivers) and communication issues (development, expressive, receptive; 72-83%). Qualitative results showed the need for trial outcomes that recognize the impact of DS on the whole family. Parents eventually hope for trials including children of all ages and were both excited about the potential positive impact of a one-time disease-modifying therapy and mindful of potential long-term implications. Participants reflected on the details and risks of a clinical trial design (e.g., sham procedures) and described the different factors that relate to their decision to participate in a trial. Their main aspirations were to stop neurodevelopmental stagnation, to reduce seizures, and to reduce the impact on their families' wellbeing. To our knowledge, this is the first study within a patient-oriented research framework that specifically explored parents' needs and perceptions regarding clinical trials of a potential disease-modifying therapy for children with a severe, developmental disease, such as DS.

The clinical, economic, and humanistic burden of Dravet syndrome – A systematic literature review

“…Health-related quality of life (HRQoL), defined as the impact of health status on an individual's or groups' well-being over time [24], among individuals living with DS is significantly lower compared with the general population [25]. Caring for people living with DS exerts substantial physical, emotional, and time burdens on the entire family unit [26][27][28][29][30][31]. While the detrimental effects of informal caregiving on caregivers' mental health and HRQoL have been shown, no systematic review has summarized the substantial humanistic burden reported among those living with DS.…”

Case report: Dravet syndrome, feeding difficulties and gastrostomy

“…Reducing seizure burden in DS has beneficial effects beyond seizure control, including improvements in cognition, language and mobility ( 35 ), but there is insufficient evidence to suggest that treatment with antiseizure medications have a direct influence on other wider disease manifestations, such as neurodevelopmental, behavioral, motor, sleep and feeding difficulties. Disease-modifying therapies, currently undergoing clinical trials, have the potential to address the full spectrum of symptoms in DS as they directly target the underlying disease pathophysiology ( 18 ). Whilst these novel therapies are undergoing development, it is important for those caring for people with DS to consider the full spectrum of comorbid conditions that occur, and ensure that all aspects of the disease are addressed where possible.…”

“…Whilst these novel therapies are undergoing development, it is important for those caring for people with DS to consider the full spectrum of comorbid conditions that occur, and ensure that all aspects of the disease are addressed where possible. Caregivers have emphasized that therapies that address the wider spectrum of comorbidities in DS (alongside seizures) will improve quality of life for people with DS and have a positive effect on family wellbeing ( 18 ).…”

Hope in the uncertainties and certainty for parents of children with rare neurological disorders. Part I (of 3): Uncertainty

“…Access to information on clinical trials, as with most rare diseases, is difficult to navigate and complex to interpret. 16,17 Instead of a new certainty, a 'diagnosis' spawns new questions, with clinicians struggling to give concrete information to families, who are left bewildered by complex genetic conditions; their names, mechanisms of inheritance, limited information regarding the future and no clearly curative therapies. 5,9 There has been a slow realisation that the new knowledge has not yet delivered a comprehensive and communicable understanding and suite of treatments.…”

“…Other than a handful of metabolic DEEs, none have a clear ‘cure’. Access to information on clinical trials, as with most rare diseases, is difficult to navigate and complex to interpret 16,17 …”