title: Design issues in a prospective randomized double-blinded trial of prophylaxis with fluconazole versus voriconazole after allogeneic hematopoietic cell transplantation.
abstract: BACKGROUND
  Aspergillus infections pose the toughest infectious challenges to the clinician caring for hematopoietic cell transplant recipients. About 15% of patients become infected, with a case fatality rate of approximately 65%. To date, no effective prophylactic strategies have been developed.
  
  
  METHODS
  Voriconazole, a recently licensed extended-spectrum azole, with demonstrated efficacy against aspergillus, is currently being tested as a potential prophylactic agent against aspergillus and other invasive fungal infections. Logistic issues--such as patient selection, choice of comparator, blinding of study drugs, duration of study drug administration, and how to handle empirical amphotericin B for possible invasive fungal infections--and analytic concerns, including choice and definition of the primary end point and the potential confounding effect of informative censoring (as a result of noninfectious events), were considered in the design of the clinical trial.
  
  
  RESULTS
  The trial is now under way, with a projected 3-year enrollment period.
  
  
  CONCLUSIONS
  Each design decision shaped the trial in a way that permitted certain questions to be answered while not allowing others to be addressed. Once completed, the trial's results must be interpreted in light of these design details.
authors.affiliation: Department of Medicine, Blood and Marrow Transplant Program, Division of Hematology/Oncology, University of Florida Shands Cancer Center, Gainesville, FL 32610, USA. wingajr@medicine.ufl.edu
authors.forename: John R
authors.initials: JR
authors.lastname: Wingard
mesh_terms: D000935:Antifungal Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D015725:Fluconazole / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D009181:Mycoses / Q000209:etiology / Q000517:prevention & control*; D011743:Pyrimidines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D014182:Transplantation, Autologous / Q000009:adverse effects; D014184:Transplantation, Homologous / Q000009:adverse effects; D014230:Triazoles / Q000627:therapeutic use*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D015725:Fluconazole; D065819:Voriconazole