title: Forum report: issues in the design of trials of drugs for the treatment of invasive aspergillosis.
abstract: A recent trial of drugs for invasive aspergillosis was used as a background for discussing critical features in the design of antifungal trials. The study under discussion allowed stopping either drug without classifying the patient as having treatment failure, so the trial should be understood as a comparison of 2 treatment strategies, not just 2 drugs. Although the study was a noninferiority trial, the outcome permitted a claim of superiority. Use of the category of "probable" in addition to "proven" aspergillosis permitted inclusion of patients for whom the diagnosis was less certain but who were still early enough in the disease progression to respond to therapy. Different opinions still exist about some of the criteria for the diagnosis of "probable" aspergillosis. A blinded data review committee was helpful in evaluating efficacy in this unblinded trial but had limited value in assessing toxicity. An understanding of these features of design of antifungal drug trials is important in applying the results to clinical practice.
authors.affiliation: Clinical Mycology Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. jbennett@niaid.nih.gov
authors.forename: John E
authors.initials: JE
authors.lastname: Bennett
authors.forename: John
authors.initials: J
authors.lastname: Powers
authors.forename: Ben
authors.initials: B
authors.lastname: de Pauw
authors.forename: William
authors.initials: W
authors.lastname: Dismukes
authors.forename: John
authors.initials: J
authors.lastname: Galgiani
authors.forename: Michel
authors.initials: M
authors.lastname: Glauser
authors.forename: Raoul
authors.initials: R
authors.lastname: Herbrecht
authors.forename: Carol
authors.initials: C
authors.lastname: Kauffman
authors.forename: Jeannette
authors.initials: J
authors.lastname: Lee
authors.forename: Peter
authors.initials: P
authors.lastname: Pappas
authors.forename: John
authors.initials: J
authors.lastname: Rex
authors.forename: Paul
authors.initials: P
authors.lastname: Verweij
authors.forename: Claudio
authors.initials: C
authors.lastname: Viscoli
authors.forename: Thomas
authors.initials: T
authors.lastname: Walsh
mesh_terms: D000935:Antifungal Agents / Q000627:therapeutic use*; D001228:Aspergillosis / Q000175:diagnosis / Q000188:drug therapy*; D035843:Biomedical Research; D002986:Clinical Trials as Topic; D006801:Humans; D018579:Patient Selection; D012107:Research Design
chemical_list: D000935:Antifungal Agents