Abstracts

Rationale: Describe and discuss Medical Monitor (MM) team spirit and approach, clinical trial related considerations, encountered challenges, their solutions and mitigations, notable successes and lessons learned in MM day-to-day activities with sites and project teams while monitoring rare epilepsy clinical trials.

Methods: Several Phase III, multinational rare epilepsy syndromes trials, enrolled over 600 patients, conducted in over 170 sites in 15 countries, in The Americas, Europe, Australia and Japan, with Contract Research Organization performing selected services including Clinical Operations and Medical Monitoring and Scientific Management full service.

Results: Epilepsy trials need to reduce patient heterogeneity to achieve reliable results and complete recruitment: patients with substandard history that may be included need to be re-screened if ineligible during initial screening. MMs input to site selection/feasibility to target right population, Principal Investigator (PI)/Key Opinion Leader (KOL) expertise and active collaboration/follow up was crucial. To reduce variability associated with seizure misclassification in epilepsy trials, independent seizure reviewers are involved and site trained focusing on study-specific seizures and detailed process of ongoing seizure review and re-classification if needed. MMs actively supported review of protocol inclusion/exclusion criteria, eligibility and diagnostic review forms, and Epilepsy Consortium electronic seizure diary review and queries. MMs led on-going site/PI/KOL communications with Question and Answer sessions and peer-to-peer lessons learned were discussed. Additionally, Medical Monitors conducted 1:1 calls with PIs/KOLs. Study drug dosing compliance and patient safety was of utmost importance. Prohibited medications have been monitored for protocol adherence. Project team communication, internal and external, was notably remarkable. Quarterly Newsletters to PI/sites were implemented to boost a healthy PI competition, and included MMs reviews of any significant medical topics of interest. MMs emphasize peer-to-peer communication with PI/KOLs. This medical and scientific collegial relationship and collaboration with a personal dedication of each party was important not only for excellent teamwork and cooperation of all stakeholders, but consequently also, for subjects' well-being, safety, and studies' endpoints. Medical Monitors involvement with Clinical Operations team has tremendously supported recruitment and enrollment to achieve First Patient In (FPI) on schedule and budget. Monthly Safety meetings were ongoing for medical and safety data listings review to discuss important findings and trends.

Conclusions: In this presentation, we will share our challenges in medical and scientific management of global rare epilepsy syndromes trials in children and adult population. Effective relationships between Medical Monitors, Clinical Operations team, Sponsors and the PIs/sites are noted as one of the key factors for success. The Medical Monitor lessons learned will be presented as a peer-to-peer educational effort.

Funding: Please list any funding that was received in support of this abstract.: None.