Endpoints for Clinical Trials Testing Treatment of Acute Graft- versus-host Disease: A Consensus Document

Currently, no agents are approved by the United States Food and Drug Administration for either prevention or treatment of acute graft-versus-host disease (GVHD). Since the field lacks formal precedents establishing a comparative basis for assessing the efficacy and safety of new investigational agents, the design of trials to demonstrate overall clinical benefit with statistical certainty remains extremely difficult both for academic and industry sponsors. As a step toward addressing this problem, a panel of experts met on two occasions to reach consensus on recommendations for terminology defining a clinically meaningful primary endpoint in studies assessing treatment for acute GVHD. The panel recommended terminology for “very good partial response” that includes both diagnostic and functional criteria. Assessment of response at day 28 after starting treatment is appropriate for the primary end point, but later time points can be considered. Since treatment agents can be designed for use on a single occasion, on repeated © 2009 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved. Corresponding author: Paul Martin, MD, Address: Fred Hutchinson Cancer Research Center, P.O. Box 19024, 1100 Fairview Ave. N. D2-100, Seattle, WA 98109-1024, pmartin@fhcrc.org, Phone: 206-667-4798, Fax: 206-667-5255. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Financial Disclosure Statements P.J.M. , research support from Osiris Therapeutics; C.R. B. , research support from Osiris Therapeutics; H. -G.K, independent safety monitor for a clinical trial sponsored by Osiris Therapeutics and owns < $50,000 of Osiris stock; M.W. S. , research support from Osiris Therapeutics; D.W. , research support from Amgen, Hospira, Easai, Roche, Genzyme and honoraria for advisory board participation from Genzyme, Dor, Hospira, and Osiris; R.J.S. , P.L. M. , P.S. , J.P.U. , N.J.C. , P.W. , E.J.S. and M.L. M. , no additional relevant financial disclosures. NIH Public Access Author Manuscript Biol Blood Marrow Transplant. Author manuscript; available in PMC 2010 July 1. Published in final edited form as: Biol Blood Marrow Transplant. 2009 July ; 15(7): 777. doi:10.1016/j.bbmt. 2009.03. 012. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript occasions as needed, or continuously, durability of response should not be required as a component in the primary end point of the initial trials, although follow-up trials may be needed in order to define the optimal conditions of use and the associated risks and benefits, and sustained response may be essential for optimal clinical benefit.