Issues related to the design and interpretation of clinical trials of salvage therapy for invasive mold infection Journal Article
| Authors: | Almyroudis, N. G. ; Kontoyiannis, D. P.; Sepkowitz, K. A.; DePauw, B. E.; Walsh, T. J.; Segal, B. H. |
| Article Title: | Issues related to the design and interpretation of clinical trials of salvage therapy for invasive mold infection |
| Abstract: | 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. © 2006 by the Infectious Diseases Society of America. All rights reserved. |
| Keywords: | clinical trial; mortality; review; salvage therapy; patient selection; research design; outcome assessment; morbidity; antifungal agent; drug hypersensitivity; drug research; clinical research; randomization; immune deficiency; corticosteroid; calcineurin inhibitor; disease exacerbation; mycosis; voriconazole; antifungal agents; clinical trials; immunosuppressive agent; host pathogen interaction; piperacillin plus tazobactam; amphotericin b lipid complex; confounding variable; mycoses; amphotericin b deoxycholate; amphotericin b; mould |
| Journal Title: | Clinical Infectious Diseases |
| Volume: | 43 |
| Issue: | 11 |
| ISSN: | 1058-4838 |
| Publisher: | Oxford University Press |
| Date Published: | 2006-12-01 |
| Start Page: | 1449 |
| End Page: | 1455 |
| Language: | English |
| DOI: | 10.1086/508455 |
| PUBMED: | 17083020 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 16" - "Export Date: 4 June 2012" - "CODEN: CIDIE" - "Source: Scopus" |
