Impact of Changes of the 2020 Consensus Definitions of Invasive Aspergillosis on Clinical Trial Design: Unintended Consequences for Prevention Trials?
Abstract
<h4>Background</h4>Consensus definitions for the diagnosis of invasive fungal diseases
(IFDs) were updated in 2020 to increase the certainty of IFD for inclusion in clinical
trials, for instance by increasing biomarker cutoff limits to define positivity. To
date, there is a paucity of data as to the impact of the revised definitions on clinical
trials.<h4>Methods</h4>In this study, we sought to determine the impact of the new
definitions on classifying invasive aspergillosis (IA), the most common invasive mold
disease in immunocompromised patients. We reclassified 226 proven and probable IA
cases plus 139 possible IFD cases in the Aspergillus Technology Consortium (AsTeC)
and in an antifungal prophylaxis trial (BMT CTN 0101) using the new criteria.<h4>Results</h4>Fewer
cases met the more stringent diagnostic 2020 criteria after applying the reclassification
criteria to define probable IA. Of 188 evaluable probable cases, 41 (22%) were reclassified
to 40 possible IA and 1 probable IFD. Reclassification to possible IFD occurred in
22% of hematologic malignancy (HM) patients, 29% of hematopoietic cell transplant
(HCT) patients, and in no lung transplant (LT) patients. Date of diagnosis was established
a median (range) of 3 (1-105) days later in 15% of probable IA cases using the new
criteria. Applying the new definitions to the BMT CTN 0101 trial, the power to detect
the same odds ratio decreased substantially.<h4>Conclusions</h4>The updated IA consensus
definitions may impact future trial designs, especially for antifungal prophylaxis
studies.
Type
Journal articleSubject
antifungal clinical trialsantifungal prophylaxis
antifungal treatment
invasive aspergillosis
invasive fungal diseases
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https://hdl.handle.net/10161/26026Published Version (Please cite this version)
10.1093/ofid/ofab441Publication Info
Wingard, John R; Alexander, Barbara D; Baden, Lindsey R; Chen, Min; Sugrue, Michele
W; Leather, Helen L; ... Marr, Kieren A (2021). Impact of Changes of the 2020 Consensus Definitions of Invasive Aspergillosis on Clinical
Trial Design: Unintended Consequences for Prevention Trials?. Open forum infectious diseases, 8(10). pp. ofab441. 10.1093/ofid/ofab441. Retrieved from https://hdl.handle.net/10161/26026.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Barbara Dudley Alexander
Professor of Medicine
Clinical research related to infectious complications of solid organ and bone marrow
transplantation, with a particular interest in the treatment and rapid diagnosis of
fungal disease. Training the next generation of Transplant Infectious Disease Physicians
is a special focus of mine as the Principal Investigator of our Interdisciplinary
T32 Training Program funded the NIH.

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