Clinical trial coordination of multifaceted ethical and regulatory oversight entities during the COVID-19 public health emergency

We implemented two outpatient randomized controlled trials of COVID-19 convalescent plasma during the COVID-19 public health crisis. Unique challenges included how to maneuver all the moving parts to precipitously mobilize and guide clinical teams and facilities through multiple review groups, to reach multiple target populations, and to share trial results. We describe how a flexible clinical trial coordinating center team approached and robustly coordinated multiple regulatory agencies and protocol changes to keep up with rapidly changing pandemic conditions and knowledge. Four agencies oversaw ethical and regulatory reviews for 26 participating sites, two protocols, and two master informed consent forms, in English and Spanish, through a two-month start-up cycle and 68 protocol and consent form changes, culminating in a national conversation of positive trial results presented in a public forum by the site investigators to trial participants. Ethical and regulatory reviews were at a faster than usual pace, sites were ready to activate in 12-15 days, and about 2 % of those transfused used Spanish language materials. Although these extraordinary practices cannot become standard, they can provide lessons for normal and emergency trial conduct. From a clinical trial coordinating center viewpoint, we recommend developing emergency interagency standard operating procedures (SOPs) for coordinating protocol reviews and emergency ceding guidelines among agencies when multiple regulatory reviews are required. English and non-English Informed Consent Forms (ICFs) developed centrally and in parallel and including a return of trial results to participants as a contact option should help trials improve participant-centered outreach.