Clinical Trial Outcome Measurements in Lennox-Gastaut Syndrome and Their Application to the Development of Targeted Treatments

Purpose of Review Lennox-Gastaut syndrome (LGS) is an epileptic encephalopathy that is challenging to treat, with >80% of patients remaining refractory to therapy. Patient-oriented clinical outcome measures are essential for treatment guidance and the development of new therapies. Here, we provide a comprehensive review of outcome measures used in clinical trials targeting patients with LGS, in order to inform future studies, develop, and implement targeted patient and caregiver-relevant outcome measures. Recent Findings Published clinical trials that include, or specifically target, individuals with LGS are reviewed, and primary and secondary outcome measurements are examined. Outcome measures are grouped and discussed as (1) seizure-related, (2) cognitive, (3) functional, (4) quality of life, and (5) psychosocial for both the LGS patient and caregiver. In patients with LGS, seizure frequency is the most common outcome measured by clinicians, while quality of life and psychosocial effect of treatments are often most important to families. Therefore, a disconnect exists between outcome measurements used in clinical trials and those rated important by families. Furthermore, cognitive, functional, and psychosocial outcome measures are often insufficiently sensitive for many LGS patients, and thus, using better targeted measures may result in an increased availability of treatment options.