Randomized controlled trials of treatments for hematologic malignancies: study characteristics and outcomes

BACKGROUND: Although randomized controlled trials (RCTs) require a great deal of time, money, and effort, the majority of them have resulted in failure to verify a priori hypotheses. Therefore, the intention in the current study was to clarify the differential elements of studies with 'positive' and 'negative' outcomes. METHODS: The authors performed a comprehensive search of RCT reports on treatments for hematologic malignancies published between 1995 and 2004, with 264 reports eventually identified. The expected rate and the observed rate for the primary endpoint were compared for 70 studies with all relevant information available. RESULTS: Of all the superiority trials (n = 256), positive studies accounted for 33%. Most of the major study characteristics were not found to be associated with the study outcome except for the primary endpoint. Studies evaluating event-free survival were more likely to report positive results than were those evaluating overall survival (P = .061). For the experimental treatment arm, the mean difference between the expected and observed rates was -10.1% (standard deviation [SD], 10.1%) in the negative studies, which indicates a rate lower than expected, and was 1.3% (SD, 9.2%) in the positive studies (P < .0001). In contrast, no statistical significance was observed for the standard treatment arm because the mean difference was 6.3% (SD, 10.7%) for the negative studies and 3.0% (SD, 9.0%) for the positive studies (P = .1885). The journal impact factor was statistically significantly higher for the positive than for the negative reports (P < .0001). CONCLUSIONS: Giving adequate consideration to the estimated effect of an experimental therapy may be critical when planning an RCT.