In today’s blog we are recapping a recent publication by Cohen et al that reported the results of a study aimed at better understanding the relationship between quality of life and other measures of health and well-being in individuals with severe genetic developmental epilepsies (called developmental and epileptic encephalopathies, or “DEEs”). The Dravet Syndrome Foundation helped to promote this survey, and 13% of the responses represented caregivers to individuals with an SCN1A genetic diagnosis.
Cohen, S.R., Helbig, I., Kaufman, M.C., Myers, L.S., Conway, L., Helbig, K.L. Caregiver assessment of quality of life in individuals with genetic developmental and epileptic encephalopathies. Dev Medicine Child Neurology. 2022;00:1-8. https://doi.org/10.1111/dmcn.15187
Why study Quality of Life measures? Seizures are the most commonly measured symptom in clinical trials for patients with Dravet syndrome and other genetic DEEs, but as families in this community know, seizures are not the only representation of disease severity. The many other comorbid conditions and symptoms beyond seizures can greatly impact the quality of life of patients, but they are not generally included as a primary outcome measure in clinical trials. Developing standardized ways to better measure quality of life in patients with DEEs- and verifying that they are accurately measuring what researchers intend- can strengthen the ability of clinical trials to assess how a therapy or intervention impacts quality of life. Correlating quality of life with other measures may also help better reveal which symptoms could be most impactful to focus on in trials.
How did the researchers study Quality of Life in the DEEs? This study used a measurement tool called the Quality of Life Inventory-Disability (or “QI-Disability”) in combination with a larger questionnaire to understand how well the QI-Disability score aligned with the level of overall burden from the underlying DEE diagnosis. The survey ran from September to December 2020 and received 174 responses, 23 from caregivers representing a patient with a diagnosis of Dravet syndrome.
In the DEEs, improved quality of life is more closely linked to the daily level of disruptions caused by seizures than to overall seizure frequency or freedom. Surprisingly, the researchers found that the quality of life score was not related to seizure frequency. Patients with long periods of seizure freedom were not more likely to have a higher quality of life than those who experienced seizures. However, what the researchers did find to be related to a higher quality of life score was the number of days that were “minimally disrupted by seizures.” Using a measure of the daily disruptive impact of seizures may be more representative of overall quality of life than counting seizure numbers and seizure-free days.
Medication side effects and comorbid diagnoses are more often associated with lower quality of life scores. The researchers also found that patients reported to be experiencing medication side effects were more likely to have a lower quality of life score. Additionally, comorbid conditions including motor delay, global developmental delay, intellectual disability, among others, were also more likely to be associated with lower quality of life scores, particularly when present in combination.
The DEEs have a great unmet need to better address quality of life. Notably, the average quality of life score for the DEEs included in this study were lower than many other neurodevelopmental disorders such as Rett syndrome, cerebral palsy, autism spectrum disorder, and Down syndrome. This underlines the large unmet need for better treatments and supports for patients living with these severe epilepsies.
This research highlights the need for better measurements that represent meaningful changes for individuals with DEEs and their families. The results suggest that the most common primary outcome measure (seizure frequency) used in clinical trials for these disease populations may not be the most representative of impacts to patient quality of life. While these results are only representative of a small subset of patients across several different DEEs, it still represents a common theme of impacts that stretch beyond seizure frequency that should be more closely studied in these patient populations. Inclusion of outcome measures that better capture symptoms that have greater impacts on patient quality of life should be strongly considered.
Special thanks to the caregivers who participated in this research. While filling out surveys can be time consuming and taxing, contributing to these efforts can lead to real impacts on the way patient care and therapeutic development progress. We are also grateful to the researchers for acknowledging the patient community and sharing their work back with the public. DSF does our best to be thoughtful about the research opportunities we promote, and it is always great to see impactful work published from those research efforts.