Ensuring Patient Safety and Data Integrity in Clinical Trials for the Treatment of Bronchiolitis Obliterans Syndrome (BOS) during the COVID-19 Pandemic

PURPOSE: The current COVID-19 pandemic has posed challenges to the conduct of clinical trials. BOSTON-1 and BOSTON-2 are two ongoing phase III, prospective, multicenter, randomized, controlled clinical trials aimed at demonstrating the effectiveness and safety of inhaled L-CsA in patients with BOS following single (BOSTON-1) or double (BOSTON-2) lung transplantation. BOSTON-3 is an open label extension trial for patients who have completed the 48-week treatment period in BOSTON-1 and BOSTON-2 trials. Several Health Authorities and Scientific Societies, including ISHLT, have issued guidance on how to ensure trial participants’ safety and compliance with Good Clinical Practice, while maintaining trial integrity during the pandemic. For BOS patients, the current situation is especially challenging because of their immunocompromised status. Thus, the trial Sponsor conducted a risk assessment to address challenges for trial conduct during restrictions posed by the pandemic and developed a contingency plan ensuring patient safety, data integrity and treatment continuation. METHODS: Due to possible restrictions of protocol-scheduled on-site visits, a contingency plan centered around remote visits has been implemented. Patients are contacted by the Investigator and/or appropriately qualified site personnel to assess the patients’ overall status, wellbeing, and document any potential adverse events (AEs). A process for trial medication shipment from the study site directly to the patient's home was set up, ensuring compliance with all regulatory requirements. Of the utmost importance, the protocols have been amended to include spirometry assessments carried out through a portable spirometer with standardized guidance by study staff and patients. ENDPOINTS: With this approach the Sponsor intends to ensure the patients’ safety and address any limitations to travel and access to investigational sites, while reducing the amount of missing data. The Sponsor implemented ISHLT recommendations to minimize hospital visits and monitor patient's status through home spirometry.