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Large retrospective effects, clear differences in animals, and multiple negative randomised controlled trials: this is exactly how it is supposed to work.

A series of randomised controlled trials (RCTs) have recently been completed regarding the clinical relevance, or lack thereof, of the "age of blood" in red blood cell (RBC) transfusion 1-5 . The results of the most recently completed study, the INFORM trial ("Informing Fresh versus Old Red cell Management"), were presented during the Plenary Session of the 2016 American Association of Blood Banks (AABB) meeting, and the paper is now available in the New England Journal of Medicine 3 . To date, none of these RCTs have detected any significant differences in the medical outcomes measured following transfusion of fresh RBCs vs standard issue (i.e. "older") RBCs. Although no study has purposefully transfused the oldest possible RBCs (i.e. 42 days) to any patient population, analyses of those who did receive the oldest units by chance likewise failed to detect any significant differences in any evaluated clinical outcome, although, the latter analyses did not have a great deal of statistical power. These results have led to some concern regarding the discrepancy between the new results with RCTs and prior results from observational studies in human patients and prospective studies with healthy human volunteers and animal models. For example, why did the study by Koch et al. 6 , and many other studies, observe increased morbidity and mortality associated with transfusions of longer-stored RBC units? In addition, why has so much animal