Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria

Abstract

Invasive fungal diseases (IFDs) have become major causes of morbidity and mortality among highly immunocompromised patients. Authoritative consensus criteria to diagnose IFD have been useful in establishing eligibility criteria for antifungal trials. There is an important need for generation of consensus definitions of outcomes of IFD that will form a standard for evaluating treatment success and failure in clinical trials. Therefore, an expert international panel consisting of the Mycoses Study Group and the European Organization for Research and Treatment of Cancer was convened to propose guidelines for assessing treatment responses in clinical trials of IFDs and for defining study outcomes. Major fungal diseases that are discussed include invasive disease due to Candida species, Aspergillus species and other molds, Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis. We also discuss potential pitfalls in assessing outcome, such as conflicting clinical, radiological, and/or mycological data and gaps in knowledge.

Conflict of interest statement

Potential conflicts of interest. B.H.S. has served on speakers' bureaus for Merck and Pfizer and on advisory committees for Pfizer, Berlex, and Schering Plough. B.E.d.P. has served on speakers' bureaus for Gilead, Merck, and Pfizer and on the advisory board for Basilea Pharmaceutical. J.R.P. has served on advisory boards for Schering-Plough, Enzon, Astellas, Merck, and Pfizer. D.P.K. has served on advisory boards for Schering-Plough, Pfizer, Astellas, Enzon, and Merck. C.A.K. has served on speakers' bureaus for or received research grants from Merck, Schering-Plough, and Astellas. L.O.-Z. has received research grants from Astellas, Merck, Pfizer, Associates of Cape Cod, and Rockeby and has served on speakers' bureaus for Astellas, Merck, Pfizer, Enzon, and Gilead. J.R.W. has served as a consultant for Merck, Pfizer, and Schering-Plough and has served on the speakers' bureaus for or received honoraria from Merck, Pfizer, Schering-Plough, and MGI Pharma. J.R.G. has served on the speakers' bureau for Merck; has received research funding from Merck and Schering-Plough; has served as a consultant for Merck, Schering-Plough, F2G, and Nektar; and has served on the advisory board for Schering-Plough. D.A.S. has served on advisory boards for Enzon and Gilead. L.J.W. is the President of MiraVista Diagnostics/MiraBella Technologies, which manufactures Histoplasma and Aspergillus antigen tests. E.J.B. has received research grants from Pfizer, Schering-Plough, Astellas, Wyeth, and Amgen and has worked as a consultant for Pfizer, Schering-Plough, Astellas, Wyeth, and Amgen. J.S. has received research grants from Pfizer, and Merck; has served on advisory boards for Merck and Pfizer; and has served on speakers' bureaus for Merck, Pfizer, and Schering-Plough. C.C. has received research grants from Pfizer, Merck Sharp & Dohme-Chibret, Gilead, and Schering-Plough and has served as a consultant for Gilead, Schering-Plough, and Zeneus Pharma. C.V. has served on speakers' bureaus for Merck, Pfizer, Schering-Plough, and Gilead; has served on advisory boards for Merck, Pfizer, Schering-Plough, Gilead, and Astellas; and has received research grants from Gilead, Abbott, Boe-heringer-Ingelheim, and Pfizer. P.G.P. has received research grants from Merck, Pfizer, SPRI, and Astellas; has served on speakers' bureaus for Merck, Pfizer, and Astellas; and has been an ad hoc advisor for Merck, SPRI, Pfizer, Astellas, Novartis, and Eisai. J.M. has served on advisory boards for Pfizer, Gilead, Merck Sharp & Dohme, Schering-Plough, Zeneus, and Astellas. B.-J.K. has served as a consultant for Basilea, F2G, Novartis, Pfizer, and Schering-Plough and has served on speakers' bureaus for MSD, Pfizer, and Schering-Plough. T.F.P. has served as a consultant for Merck, Pfizer, Schering-Plough, Basilea, Nektar Therapeutics, and Stiefel Laboratories and has served on speakers' bureaus for Merck and Pfizer. T.C. has received research grants from Merck Sharp & Dohme-Chibret, Essex Schering, Roche Diagnostics, Wako, and BioRad and has served as a consultant for Merck Sharp & Dohme-Chibret, Pfizer, Novartis, Essex Schering, Roche Diagnostics, and Cephalon. B.D. has served as a consultant for Schering-Plough, Astelas, Merck, Valeant, and BioAlliance. All other authors: no conflicts.