Double‐Blind Active‐Control Trials: Beware the Comparator You Keep

Mark J. DiNubile
2008 Clinical Infectious Diseases  
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 mucosal
more » ... is in patients with advanced human immunodeficiency virus infection were retrospectively analyzed. We compared patients who received 50 mg of caspofungin per day in a double-blind trial that used fluconazole as the comparator with patients who received the corresponding dosage in 2 similar earlier studies that used amphotericin as the comparator. With respect to the incidence of drug-related fever, the difference between the concurrent caspofungin and fluconazole groups was less than the difference between caspofungin groups from studies that used different comparators. In phase II/III blinded, active-control trials, the reporting of adverse experiences attributed to a first-in-class drug might be confounded to a variable degree by expectations regarding a well-known comparator.
doi:10.1086/592068 pmid:18781878 fatcat:ys2zvn62end5dk44x7mmmm2u7u