ASSESSMENT OF TWO CLINICAL TRIALS

Abstract

Two recent studies have examined the efficacy of interferon-gamma in reducing infection and death in patients sustaining severe injury. Both included multi-center, randomized, double-blinded placebo-control design. The first trial, conducted at four university trauma centers, enrolled 213 patients, while the second trial involved nine university trauma centers and 416 subjects. Recombinant human interferon-gamma (100 micrograms) was administered subcutaneously daily for 10 days in the first trial and 21 days in the second, in addition to standard supportive therapy. In both trials infection rates were similar in the treatment arms. Although the death rate related to infection was not affected in the first study, the second trial suggested an improved outcome from this complication. The outcome of the larger trial was flawed by dominant findings at one center that had the highest enrollment, infection, and death rates. Confounding variable analysis presented here explains much of the difference between center findings in the larger trial. Thus, the benefit of interferon-gamma as an immune adjuvant in severe injury is clouded by study design flaws evaluating its use and by the inability to identify appropriate subjects using clinical criteria.