Negative results of randomized clinical trials published in the surgical literature: Equivalency or error?

Hypothesis: We hypothesized that review of randomized controlled clinical trials (RCTs) with nonstatistically significant or "negative" results published in the surgical literature do not have appropriate statistical power to demonstrate equivalency between treatment arms. Data Sources and Study Selection: The MEDLINE database was searched to obtain reports of all RCTs with negative results published in 3 surgical journals from 1988 to 1998. Manual review of one year (1997) of publications for each journal was performed to validate our search strategy. Equivalency was evaluated using the Two One-Sided Tests Procedure and post hoc power calculations. Data Synthesis: Ninety reports of RCTs with negative results were identified in the surgical literature between 1988 and 1998. The manual review of 1997 showed a 100% retrieval rate for our search strategy. After applying the Two One-Sided Tests Procedure, 35 reports (39%) met the criteria for demonstrating equivalency. The other 55 reports (61%) contained at least a 10% absolute difference in the 90% confidence interval of Δ. Using the power calculation method, only 22 (24%) articles had a power greater than .80 to detect a 50% difference in therapeutic effect. Only 29% of the reports included a formal sample size calculation and these studies were more likely to demonstrate equivalency than those without a sample size estimate (P<.01). Conclusions: Many reports from negative RCTs published in the surgical literature lack sufficient statistical power to establish that clinically important differences are not present. Surgeons should perform appropriate sample size calculations when designing RCTs and recognize the utility of confidence intervals when reporting negative results.