Impact of Changes of the 2020 Consensus Definitions of Invasive Aspergillosis on Clinical Trial Design: Unintended Consequences for Prevention Trials?

Autor:	Kieren A. Marr, Angela M. Caliendo, Helen Leather, M. Hong Nguyen, Min Chen, Cornelius J. Clancy, Lindsey R. Baden, John R. Wingard, Brent R. Logan, Mary M. Horowitz, Michele W. Sugrue, Barbara D. Alexander, David W. Denning, L. Joseph Wheat, Francisco M. Marty
Rok vydání:	2021
Předmět:	medicine.medical_specialty invasive aspergillosis business.industry Clinical study design medicine.medical_treatment antifungal clinical trials invasive fungal diseases Odds ratio Hematopoietic stem cell transplantation Disease Aspergillosis medicine.disease Clinical trial Editor's Choice antifungal treatment Infectious Diseases AcademicSubjects/MED00290 Oncology antifungal prophylaxis Internal medicine medicine Major Article Biomarker (medicine) Prevention trials business
Zdroj:	Open Forum Infectious Diseases
ISSN:	2328-8957
Popis:	Background 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. Methods 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. Results 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. Conclusions The updated IA consensus definitions may impact future trial designs, especially for antifungal prophylaxis studies. Using more stringent consensus diagnostic definitions for Invasive Aspergillosis, more than 20% of cases in hematopoietic cell transplant and hematologic malignancies patients that met earlier definitions no longer meet diagnostic criteria. This has important implications for antifungal prevention trials.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7bcad4d6e126828a1eb444bc11789bc4 https://pubmed.ncbi.nlm.nih.gov/34631917 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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