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The indirect impact of the known comparator drug in double-blind comparative clinical trials of novel agents is underappreciated, despite its potentially pernicious effects. This hypothesis-generating analysis illustrates potential spillover effects of a comparator (amphotericin) in the evaluation of the first member (caspofungin) of a novel class (echinocandins) of antifungal drugs. Reported rates of drug-related fever in the first 3 studies of caspofungin for the treatment of mucosaldoi:10.1086/592068 pmid:18781878 fatcat:ys2zvn62end5dk44x7mmmm2u7u