Clinical Contextualization and the Assessment of Adverse Events in HBOC Trials

Abstract

Abstract: Establishing an acceptable safety and efficacy profile for hemoglobin based oxygen carriers, HBOCs, is essential. Understanding the data that describes an HBOC “safety profile” requires consideration beyond counting “events” typically associated with intent to treat analysis. The imputation of causation from numerical counts alone, without clinical context, is an incomplete description of a complex situation. Clinical contextualization provides a greater understanding of the clinico-pathological processes involved. Generating alternative hypotheses for the origin of the events, apart from the drug, patient co-morbidities, situational and disease demands, could include protocol design, failure to provide mitigation strategies, patient management issues, or inadequate education of investigators. How clinical contextualization can provide insight for the interpretation of significant safety profile events is discussed in the context of a large phase III clinical trial where an appreciation of factors underlying the differences between intent to treat analysis and other approaches is discussed.