Pitfalls in the Design of Clinical Trials for Prevention or Treatment of Acute Graft-versus-Host Disease

This review addresses pitfalls of clinical trials to evaluate new approaches for prevention or treatment of graft-versus-host disease. Determination of end points poses a difficult challenge in the design of clinical trials, and examples from previous studies are used to illustrate some of the pitfalls. Also discussed is the need for a new conceptual approach for evaluation of graft-versus-host disease after nonmyeloablative conditioning regimens, because the donor antirecipient alloimmune reaction is the primary mechanism of benefit with this type of treatment. Finally, investigators should be aware of regulatory and socioeconomic pitfalls that apply to all clinical trials.