title: Considerations in clinical trials of combination antifungal therapy.
abstract: The cure rate for serious fungal diseases with currently available agents used as monotherapy is not optimal. The introduction of new classes of antifungal drugs in the last few years naturally leads to the hypothesis that antifungal drugs used in combination may be more effective than the same drugs used alone. The design and interpretation of combination therapy studies raise challenges beyond those encountered when drugs are studied as monotherapy in the treatment of a disease. The definition of combination therapy, the study design, the selection of appropriate patient populations, and the selection of end points, as well as practical considerations, are all important in the design and interpretation of clinical trials of combination therapies. Although combination therapies hold the promise of improved efficacy, it is important to prove this hypothesis, because they also may be associated with increased toxicity and increased drug costs. A careful consideration of study design factors before the initiation of a trial will help obtain the most useful information for patients in this important area.
authors.affiliation: Antimicrobial Drug Development and Resistance Initiatives, Center for Drug Evaluation and Research, US Food and Drug Administration, Rockville, Maryland 20850, USA. powersjoh@cder.fda.gov
authors.forename: John H
authors.initials: JH
authors.lastname: Powers
mesh_terms: D000935:Antifungal Agents / Q000009:adverse effects / Q000627:therapeutic use; D002986:Clinical Trials as Topic / Q000379:methods*; D016527:Drug Costs; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D009181:Mycoses / Q000188:drug therapy / Q000517:prevention & control; D018579:Patient Selection; D011315:Preventive Medicine; D012107:Research Design
chemical_list: D000935:Antifungal Agents