title: The debate: a case for randomized controls in invasive aspergillosis.
abstract: Randomized trials in invasive aspergillosis have evolved over the past decade. Definitions of disease now include specifics of the underlying disease and how this affects interpretation of certain tests, including high resolution computed tomography and smears or cultures of sputum and bronchoalveolar lavage. Study hypotheses have changed from underpowered superiority trials to adequately powered noninferiority trials. Consensus building between Europe and North America has allowed trials to be conducted with the same protocol in both regions, thereby increasing study enrollment. In aggregate, the following outcomes can be drawn from randomized trials: (i) Liposomal amphotericin B is possibly superior to conventional amphotericin B at 14 days and less toxic. Whether the dose of liposomal amphotericin is 1 or 4 mg/kg daily is not as important as other factors in determining outcome of possible aspergillosis; (ii) amphotericin B colloidal dispersion is less nephrotoxic but has more acute infusion-related reactions than conventional amphotericin B; (iii) starting treatment with voriconazole is superior to starting with conventional amphotericin B. In an era of increasing cost containment, it will be the randomized trials that provide the clinician with the information needed to avoid inappropriate use of expensive drugs and drug combinations.
authors.affiliation: Clinical Mycology Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. jbennett@niaid.nih.gov
authors.forename: John E
authors.initials: JE
authors.lastname: Bennett
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy*; D002985:Clinical Protocols; D006801:Humans; D016032:Randomized Controlled Trials as Topic
chemical_list: D000935:Antifungal Agents