TY - JOUR
T1 - Issues related to the design and interpretation of clinical trials of salvage therapy for invasive mold infection
AU - Almyroudis, Nikolaos G.
AU - Kontoyiannis, Dimitrios P.
AU - Sepkowitz, Kent A.
AU - DePauw, Ben E.
AU - Walsh, Thomas J.
AU - Segal, Brahm H.
N1 - Funding Information:
member of the speakers bureau of Astellas Pharma. B.H.S. has received laboratory support from Astellas Pharma, reimbursement from Sch-ering-Plough for serving on their Data Review Committee, and speakers’ honoraria from Merck and Pfizer. D.P.K. has received recent research funding from Merck, Enzon Pharm, and Astellas Pharma; is a consultant for Merck and Schering-Plough; is a member of the advisory boards of Merck and Schering-Plough; and has received speakers’ honoraria and is a member of the speakers bureau for Merck, Enzon Pharm, and Astellas Pharma. All other authors: no conflicts.
PY - 2006/12/1
Y1 - 2006/12/1
N2 - Invasive mold infection is a major cause of morbidity and mortality among severely immunocompromised individuals. We discuss the challenges involved in the design and interpretation of salvage antifungal trials, focusing on mold infection. We suggest that patients with refractory fungal infection be analyzed separately from those with intolerance to standard regimens because of the poorer prognosis of the former group. We propose a composite outcome assessment in which refractory infection is defined as infection associated with the worsening of at least 2 of the following 3 types of criteria: clinical, radiologic, and mycologic. Confounding variables, including heterogeneity in host factors, initial antifungal therapy, and selection bias, are discussed. Although randomized studies would provide the most credible results, the lack of an adequate number of patients to meet prespecified stratification criteria for all confounding variables makes such studies impractical. Given that randomized studies are unrealistic, studies involving carefully selected, matched, contemporaneous control subjects are likely to be the most useful alternative.
AB - Invasive mold infection is a major cause of morbidity and mortality among severely immunocompromised individuals. We discuss the challenges involved in the design and interpretation of salvage antifungal trials, focusing on mold infection. We suggest that patients with refractory fungal infection be analyzed separately from those with intolerance to standard regimens because of the poorer prognosis of the former group. We propose a composite outcome assessment in which refractory infection is defined as infection associated with the worsening of at least 2 of the following 3 types of criteria: clinical, radiologic, and mycologic. Confounding variables, including heterogeneity in host factors, initial antifungal therapy, and selection bias, are discussed. Although randomized studies would provide the most credible results, the lack of an adequate number of patients to meet prespecified stratification criteria for all confounding variables makes such studies impractical. Given that randomized studies are unrealistic, studies involving carefully selected, matched, contemporaneous control subjects are likely to be the most useful alternative.
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U2 - 10.1086/508455
DO - 10.1086/508455
M3 - Review article
C2 - 17083020
AN - SCOPUS:33751577974
SN - 1058-4838
VL - 43
SP - 1449
EP - 1455
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 11
ER -