Abstracts

Rationale: Cyclin-dependent kinase-like 5 (CDKL5) Deficiency Disorder (CDD) is a rare neurological condition caused by a mutation in the CDKL5 gene. Features of this condition include early-onset epilepsy, severe global developmental delay and impaired gross motor function. There is evidence of large variability of severity of symptoms between individuals with this condition, for instance, in expressive communication and motor abilities. Therefore, understanding the disease symptoms and impact on children will allow the development of a conceptual model to understand the nuances of the disease. This in turn may be helpful for selection of clinical outcome assessments (COA) for inclusion in future studies looking to treat this severe condition.  Methods: A review of the qualitative literature was undertaken to develop an initial conceptual model. An iterative process was then taken to refine this model through interviews with patient advocates (n = 3), key opinion leaders (KOLs) (n = 3), and pharmaceutical industry experts (n = 3). Interviews were conducted one-to-one and informed further development and modification of the model.  Results: The literature review yielded very limited information specific to the disease course (n = 12), but were used alongside the International Foundation for CDKL5 Research (IFCR) Guidance to form a draft model. Revisions were made following input from patient advocates, KOLs, and pharmaceutical experts; however, overall feedback suggested the model was comprehensive, capturing important core and associated symptoms, and inter-related impacts of the disease on children.Symptoms were grouped into the following domains: seizures, cognitive/sensory, physical health/autonomic, motor functioning, with the core symptoms being proposed as: seizures, cortical visual impairment, limited or absent speech, intellectual impairment, gastrointestinal problems, developmental delay, limited hand function and sleep problems/ abnormalities. Impacts were grouped into: functioning/activities of daily living, feeding, communication, physical health, and emotional and social well-being.  Conclusions: Substantial overlap exists between some of the symptoms and impacts in the model, with need for further understanding to elucidate links and interactions. Involving an advisory group enabled additional insights, which proved very useful in the refinement of the conceptual model given the limited published research due to the rare nature of the condition. However, further in-depth qualitative research with participant caregivers is needed to provide more patient-centred evidence. The initial model may be useful for those interested in monitoring patient symptoms or evaluating new treatments by informing selection of the most relevant COAs. Further research is also needed to explore the impact on the families of children with CDKL5 deficiency.  Funding: This research was funded by the Loulou Foundation