Use of an electronic seizure diary in a randomized, controlled trial of natalizumab in adult participants with drug-resistant focal epilepsy

Objective: To analyze electronic diary (e-diary) use in a phase 2, randomized, controlled clinical trial (OPUS; NCT03283371) of natalizumab in adult participants with drug-resistant focal epilepsy. Methods: We developed an e-diary, which incorporated an episodic seizure diary and a daily diary reminder, for use as the primary source to record participants' daily seizure activity in the OPUS phase 2 clinical trial. Participants and/or their designated caregivers made e-diary entries by selecting seizure descriptions generated in the participants' and/or caregivers' own words at the time of screening. Seizures and seizure-free days were reported for the current day and for up to 5 and 4 retrospective days, respectively. A record of seizure symptoms entered within the prior 5-day period was displayed on accessing the diary. Changes were not permitted in the e-diary once a seizure record was saved unless a data change request was made. A paper backup diary was available. Results: E-diary entries (N = 15,176) from the 6-week baseline period and subsequent 24-week placebo-controlled period were analyzed for 66 adults who were randomized and dosed in the OPUS trial. The overall e-diary compliance, defined as the total number of days with any entry out of the total number of days in the baseline and placebo-controlled periods for all participants combined, was 83.6%. Caregivers made 190 (1.3%) e-diary entries. Day-of-event e-diary entries totaled 11,248 (74.1%). At least one paper backup diary was used by 36 (54.5%) participants. Significance: Our data highlight that good e-diary compliance can be achieved across participants in randomized clinical trials in adult focal epilepsy. In addition to identifying and addressing any barriers that may prevent a minority of participants from achieving good e-diary compliance, consideration of e-diary elements, such as recall period and reporting of seizure-free days, will facilitate the most accurate data capture in epilepsy clinical trials. (C) 2021 Elsevier Inc. All rights reserved.