Endpoints for clinical trials testing treatment of acute graft-versus-host disease: a joint statement.
Currently, no agents are approved by the United States Food and Drug Administration (FDA) for either prevention or treatment of acute graft-versus-host disease (aGVHD). Formal precedents establishing a comparative basis for assessing the efficacy and safety of new investigational agents are still lacking. As a step toward addressing this problem, a panel of experts met on 2 occasions to reach consensus on recommendations for terminology describing a clinically meaningful primary endpoint in studies assessing treatment for aGVHD. The panel recommended terminology for "very good partial response" (VGPR) that includes both diagnostic and functional criteria. The central hypothesis leading to this proposal is that the potential harm of giving more treatment than needed to produce or maintain complete response exceeds the harm of slight undertreatment that may be associated with less than complete response. VGPR clearly cannot be used as the sole outcome measure in GVHD treatment trials, and must be considered in the context of survival and safety. The proposed use of VGPR as the primary endpoint in GVHD treatment trials will remain provisional until its use has been validated through experience.
Martin
Paul J
PJ
Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA. pmartin@fhcrc.org
Bachier
Carlos R
CR
Klingemann
Hans-Georg
HG
McCarthy
Philip L
PL
Szabolcs
Paul
P
Uberti
Joseph P
JP
Schuster
Michael W
MW
Weisdorf
Daniel
D
Chao
Nelson J
NJ
Kebriaei
Partow
P
Shpall
Elizabeth J
EJ
Macmillan
Margaret L
ML
Soiffer
Robert J
RJ
D000208:Acute Disease; D002986:Clinical Trials as Topic / Q000379:methods*; D023381:Endpoint Determination / Q000379:methods*; D006086:Graft vs Host Disease / Q000628:therapy*; D006801:Humans