Clinical Scientist II Biogen Watertown, Massachusetts
Rationale: Paper seizure diaries have historically been the most widely used instruments for recording seizure details in epilepsy clinical trials. There has been growing interest in whether electronic seizure diaries (e-diaries) may serve as a viable alternative given the potential advantages of electronic clinical outcome assessment. However, data are lacking on the performance of e-diaries in epilepsy trials. We used an e-diary to capture seizure details in the Phase 2, multicenter, randomized, double-blind, placebo-controlled OPUS study exploring the efficacy, safety, and tolerability of natalizumab over a 6-month period in adults with drug-resistant focal epilepsy. Methods: An e-diary was developed and utilized as the primary source for capturing each participant’s daily record of seizures in the OPUS study. The e-diary incorporated an episodic seizure diary and a daily diary reminder. The participant and/or designated caregiver could make e-diary entries by selecting from a list of seizure descriptions generated at the time of screening. They were asked to report seizures and seizure-free days, which could be recorded up to five and four retrospective days, respectively. A log of all seizure symptoms entered by the participant and/or designated caregiver within the prior 5-day period was displayed upon accessing the diary. Changes were not permitted in the e-diary once a seizure was saved unless a data change request was made. A paper diary back-up form was available in case a seizure, seizure-free day, or new seizure symptoms could not be entered into the e-diary. Results: The e-diary was used to capture seizure details for 66 adults who were randomized and dosed in the OPUS study. Data from 30 weeks (6-week baseline and 24-week placebo-controlled periods) were analyzed. There were 15,176 total e-diary entries, including 1,389 (9.2%) focal aware without motor, 756 (5.0%) focal aware with motor, 5,231 (34.5%) focal impaired awareness, 998 (6.6%) focal to bilateral tonic-clonic, 6,736 (44.4%) seizure-free days, and 66 (0.4%) unknown entries. The overall e-diary compliance, defined as the total number of days with entries (seizures or seizure free) out of the total number of days in the baseline and placebo-controlled periods, was 83.65% for all participants. One hundred ninety (1.3%) e-diary entries were made by caregivers. And 11,248 (74.1%) e-diary entries were made on the day of the event. Thirty-six (54.5%) participants used at least one paper diary back-up form. Conclusions: The use of e-diaries in epilepsy trials is still in its infancy. Analysis of e-diary data from randomized clinical trials is crucial to determine the specific design elements that will facilitate the accurate recording of seizure data by patients. Our results suggest that e-diaries can be successfully used by drug-resistant focal epilepsy patients, but the operational features in the e-diary, such as the reporting window, use of a paper diary or other form of back-up, an appropriate source data verification strategy, and other elements, should be carefully considered to ensure data quality. Funding: Please list any funding that was received in support of this abstract.: This study was supported by Biogen.