Rationale:
Regulators emphasize the importance of including the voice of patients and caregivers in the development of clinical outcome assessments (COAs) for use in clinical trials. It is therefore important to identify the disease- and treatment-related concepts that are important to patients and caregivers. This targeted literature review (TLR) aimed to identify signs, symptoms, and impacts associated with focal onset seizures (FOS), generalized onset seizures (GOS), and Dravet syndrome (DS) to support development of preliminary conceptual models.
Methods:
The PubMed database was searched in 2022 and 2023 for literature about the disease- or treatment-related signs, symptoms, and impacts (i.e., concepts) experienced by adult and pediatric patients with FOS, GOS, or DS. A PICOS (Population, Intervention, Comparator, Outcomes, Study Designs of Interest) framework was implemented to support the development of the search strategies. Search results were reviewed by title, abstract, and then the remaining articles underwent full text review to further confirm inclusion. Concepts were extracted from the final list of prioritized publications with a focus on qualitative research with patients and caregivers.
Results:
The review resulted in 21 articles for FOS, four articles for GOS, and eight articles for DS. For FOS, 72 signs and symptoms, including autonomic, motor, and psychologic symptoms, and 42 impacts, including cognitive, physical, and emotional impacts were identified. For GOS, 55 signs and symptoms, including seizure and seizure-related symptomatology as well as other symptoms like pain and headaches and 37 impacts to emotional, social, and other aspects of well-being were identified. For DS, 54 signs and symptoms related to seizures as well as developmental, mobility, and sleep-related symptoms and 42 impacts, including impacts to behavior, emotions, and social life, were identified. Three conceptual models were created to illustrate the experience for each of these indications of interest.
Conclusions:
The conceptual models highlight a significant number of concepts reported for individuals with FOS, GOS, or DS. This review emphasizes the heterogeneous nature of seizures and related conditions, further underscoring the complexities associated with diagnosing and treating individuals who present with these signs and symptoms and experience associated impacts. These models can be leveraged in future research as a starting point on what signs, symptoms, and impacts may be of most relevance to patients and caregivers, particularly since they illustrate that the patient experience extends beyond seizures alone and includes a broader set of concepts that need to be considered. Such future research includes interviews with patients and caregivers to gain a more complete understanding of the signs, symptoms and impacts they experience beyond the seizures themselves. These data can further inform what future clinical trials and treatments related to FOS, GOS, or DS may be able to improve in addition to seizure frequency.
Funding:
This research was funded by IQVIA, Inc.