Abstracts

Rationale: Enrollment of subjects into clinical trials of AEDs is often difficult. The reasons for the difficulty may have changed with time. Knowing the current reasons for exclusion among a population of persons with epilepsy may lead to changes in trial design or to other measures to increase enrollment. Methods: At our Level 4 epilepsy center, there are often several AED clinical trials open for enrollment. An experienced research coordinator reviews charts of clinic patients to identify potential subjects. This systematic review can identify potential subjects for multiple trials. Demographic data and reasons for exclusion are tabulated for each patient. Charts of consecutive adult return patients were examined by hand, whenever the coordinator was present in clinic. Between Nov 2018 and March 2019 (4 months), 552 persons were excluded from consideration for enrollment in one or more clinical trials. Specific reasons for exclusion were tabulated. Only the first screening review was counted, later qualification or enrollment in a different trial was not counted. When two or more reasons for exclusion were listed, a hierarchy was used to select the primary reason and to avoid double counting of individuals: seizure type, pregnancy, excluded comedications, excluded comorbidities, low seizure frequency, then all other reasons. Results: The most common primary reason for exclusion was seizure frequency too low (38.8%). The second most common was wrong seizure type (11% generalized for studies requiring focal onset seizures, 0.9% focal aware nonmotor seizures). Other reasons, as percentages, were as follows: serious comorbid medical conditions 7.4, epilepsy onset too recent 6.2, chronic benzodiazepine use 6.3 (including 3.0 clobazam), recent medication or neurostimulator adjustment 5.5, history of psychogenic nonepileptic events 5.3, use of other prohibited interacting drugs 4.0, patient preference to continue presurgical workup or had recent epilepsy surgery 3.8, cannabadiol (CBD) use (prescription or nonprescription) 3.6, severe cognitive disability 3.0, pregnant or planning pregnancy 1.4, psychosis 1.4, miscellaneous reasons 2.0. 13% of patients had two or more reasons for exclusion. Conclusions: There were many reasons that persons with epilepsy were deemed ineligible to participate in a clinical trial. Cumulatively, these reasons excluded most patients even in a specialized epilepsy clinic. Low seizure frequency, while a good thing, may not be accurate: better use of seizure diaries could help. Other trial designs, such as time to the nth seizure, could be considered. 6.6% of persons were excluded because of CBD or clobazam use, drugs unapproved for focal seizures. CBD or clobazam use was the only reason for exclusion in 75% of those taking one of these drugs. In summary, incomplete seizure counts, use of unapproved drugs, and clinician selection of prescribable drugs rather than experimental drugs are barriers to enrollment which may be amenable to improvement. Funding: No funding