Forum report: issues in the design of trials of drugs for the treatment of invasive aspergillosis.
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.
Bennett
John E
JE
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
Powers
John
J
de Pauw
Ben
B
Dismukes
William
W
Galgiani
John
J
Glauser
Michel
M
Herbrecht
Raoul
R
Kauffman
Carol
C
Lee
Jeannette
J
Pappas
Peter
P
Rex
John
J
Verweij
Paul
P
Viscoli
Claudio
C
Walsh
Thomas
T
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
D000935:Antifungal Agents