The role of hemovigilance and postmarketing studies when introducing innovation into transfusion medicine practice: the amotosalen-ultraviolet A pathogen reduction treatment model

BACKGROUND Innovations in transfusion medicine require randomized controlled clinical trials (RCTs) to demonstrate safety and efficacy before approval; however, these studies are costly and limited in scope and may be underpowered to detect rare adverse events (AEs). Regulatory agencies, such as the Food and Drug Administration, require postmarketing surveillance, hemovigilance (HV), and controlled Phase IV studies to monitor performance and confirm safety. STUDY DESIGN AND METHODS The INTERCEPT Blood System (IBS) is an illustrative model for implementation of a transformative technology for which sponsored active HV, regulatory authority HV, and Phase IV studies were used to extend preapproval efficacy and safety information. RESULTS After CE mark registration in Europe, 13,644 patients received 76,346 IBS components prepared largely without gamma irradiation or bacterial screening in sponsored active HV studies documenting no increased incidence of AEs compared to historical controls and no increased component utilization. National HV systems in France and Switzerland specifically demonstrated no transfusion-associated graft-versus-host disease or increased incidence of transfusion-associated acute lung injury, after transfusion of 317,669 IBS platelet (PLT) components, and significant reduction of transfusion-transmitted bacterial infection as well as acute transfusion reactions. Cumulatively, these studies provide new information about safety and efficacy of IBS PLT and plasma components not obtainable from RCTs. CONCLUSION Although inherently different from RCTs, properly designed postmarketing studies are informative regarding the safety and efficacy of innovative transfusion technologies in large patient populations under conditions of routine use.