The Power of Real-World Evidence In Rare and Difficult-to-treat Epilepsies

Developmental and Epileptic Encephalopathies (DEEs) are a group of rare and severe epilepsies which are characterized by seizures and significant developmental delays.¹ Most DEEs begin in early life, often in infancy, with children experiencing frequent and severe seizures, which can be of multiple types.² This generates a complex clinical picture in which both developmental abnormalities and severe epilepsy contribute to the functional impairment of these children which continues into adulthood.

These types of rare epilepsies not only impact the quality of life of the individuals living with the condition, but their caregivers and families too.^3,4

Realizing the value of Real-World Evidence in DEEs

As with all prescribed medicines, many medicines used to treat DEEs have undergone rigorous randomized controlled trials (RCTs) to determine their safety and efficacy, as well as their impact on seizure control. While RCTs are considered the gold standard for evaluating the efficacy and safety of medicines,⁵ observational studies conducted in a real-world setting are invaluable in providing context on the effectiveness of available treatments in clinical practice and in the day-to-day lives of people living with these diseases.⁶ RCTs evaluating treatments in rare epilepsies have typically focused solely on seizure control. While this is a critical outcome measure, the nature of these complex epilepsies means that the impact of the condition extends beyond seizures to cognitive and behavioral challenges including the ability to communicate and interact with others.

Intellectual disabilities experienced by people living with DEEs may make explaining their challenges, needs and treatment experience difficult. So, the family and caregiver perspective become a vital aspect of optimizing care. Collecting real world evidence on the perspective of the family/caregiver – who care for the individual most of time, provides an important view of the broader impact of a specific treatment. Family members and caregivers are uniquely equipped to notice reductions in seizure frequency and severity as well as improvements in non-seizure symptoms – which may include behavior and cognition, communication and sleep.⁷

I have seen first-hand how small changes in these beyond-seizure outcomes can make a huge difference to those living with a DEE and witnessed the great joy that can be found by families and caregivers in moments of connection or recognition between them and their loved one – a smile, the look of recognition on their face or a positive response to a caregiver’s voice or touch.

Real world evidence can take various forms: from non-interventional or open label studies to patient registries, and from electronic health record studies to patient or caregiver surveys.⁸ Due to the length of time required to complete open-label clinical studies, leveraging patient or caregiver surveys – which gather information on patient needs, preferences, experiences and quality of life – provide an invaluable opportunity to understand the real-world use of a medicine in the interim. This evidence can complement existing data from RCTs, adding to the overall bank of information available, helping clinicians to:

• understand the broader value of the treatment, through a data set which is reflective of day-to-day life; and
• use this evidence to better understand and manage the needs and expectations of those living with the condition, as well as those of their families.

We believe that translating real world evidence into actionable and clinically relevant insights is critical to cementing the future of patient-centered healthcare. We are committed to advancing this field – and to leveraging the valuable insights gleaned to optimize patient care.

Learn more about rare forms of epilepsy here.

References

¹Epilepsy Foundation. Developmental and Epileptic Encephalopathy (DEE). Further information on DEEs can be found at: https://www.epilepsy.com/what-is-epilepsy/syndromes/developmental-and-epileptic-encephalopathy. Published March 1, 2024. Accessed August 2024.  
²Raga S et al, Developmental and epileptic encephalopathies: recognition and approaches to care. Epileptic Disorders, 2021, 23: 40-52..  
³Kerr M et al, Evolution and management of Lennox-Gastaut syndrome through adolescence and into adulthood: are seizures always the primary issue?. Epileptic Disord. 2011;13 Suppl 1:S15-S26.  
⁴Jansen A et al, Burden of Illness and Quality of Life in Tuberous Sclerosis Complex: Findings From the TOSCA Study. Frontiers in Neurology. 2020, 11:904.  
⁵Tashkin DP, Amin AN, Kerwin EM. Comparing Randomized Controlled Trials and Real-World Studies in Chronic Obstructive Pulmonary Disease Pharmacotherapy. Int J Chron Obstruct Pulmon Dis. 2020 Jun 2;15:1225-1243.  
⁶Silverman SL. From Randomized Controlled Trials to Observational Studies. The American Journal of Medicine. 2009;122(2):114-120.  
⁷Dang A. Real-World Evidence: A Primer. Pharmaceut Med. 2023;37(1):25-36.  
⁸Berg, A. T., Dixon-Salazar, T., Meskis, M. A., Danese, S. R., D. Le, N. M., & Perry, M. S. Nonseizure- and seizure-related benefits of cannabidiol treatment in the real world: plain language summary of the results from a caregiver survey. Future Neurology. 2024;19(1).