Difficulties in demonstrating efficacy of blood substitutes

Currently, the fear of infectious disease transmission by allogenic blood transfusions has spurred interest in developing a blood substitute FDA approval requires that a sponsor demonstrate that the substitute is effective. The challenge in designing efficacy studies in man is proving that the substitute offers significant advantages over conventional therapies for acute blood loss. This task is complicated by the oxygen reserve and the response to hemodilution following treatment of acute blood loss in man. Paradoxically, the technique that relies on these protective physiologies-isovolemic perioperative hemodilution-many offer the best experimental model to establish efficacy of a blood substitute in man.