Inadequate statistical power to detect clinically significant differences in adverse event rates in randomized controlled trials.

OBJECTIVE: To determine the statistical power to detect potentially clinically significant differences in serious adverse events between drug therapies reported in a sample of randomized controlled trials (RCTs). STUDY DESIGN AND SETTING: Systematic review of RCTs with positive efficacy endpoint and at least a twofold difference in the proportion of patients with serious adverse events between treatment groups from six major journals. The power of each study to detect statistically significant differences in serious adverse events was calculated. RESULTS: Of the six included trials, all performed statistical analysis on adverse events without disclosure of the statistical power for detecting the reported differences between groups. The power of each study to detect the reported differences in adverse events was calculated and yielded values ranging from 0.07 to 0.37 among trials with non-statistically significant differences. CONCLUSION: Statistical testing for differences in the proportion of patients experiencing an adverse event is common in RCTs; non-statistically significant differences are associated with low statistical power. A high probability of type II error may lead to erroneous clinical inference resulting in harm. The statistical power for nonsignificant tests should be considered in the interpretation of results.

The role of statin therapy in sepsis.

OBJECTIVE: To systematically review the evidence evaluating the role of statin therapy in sepsis. DATA SOURCES: MEDLINE, EMBASE, and PubMed were searched (1980-January 2007) for English-language clinical trials that evaluated the use of statins and the development and treatment of sepsis in human subjects. Search terms included statin, HMG-CoA reductase inhibitor, bacteremia, sepsis, septic shock, septicemia, and severe sepsis. In addition, pertinent references from identified articles were obtained. STUDY SELECTION AND DATA EXTRACTION: Only clinical trials with primary efficacy outcomes of mortality, incidence of sepsis, and severe sepsis were included. DATA SYNTHESIS: Seven retrospective and 2 prospective cohort studies were included in this review. One was excluded because the patient population was not experiencing sepsis. Three studies demonstrated a reduced mortality with statin use while 2 other studies did not demonstrate this mortality benefit. One study suggested increased mortality with statin use in sepsis. Three studies showed a reduced incidence of development of sepsis or sepsis-related outcomes, while one study did not. The observational and retrospective nature of these studies and the higher rate of cardiovascular comorbidities in the statin groups may have allowed for a confounding influence. The conflicting results and heterogeneity between the studies makes the observed association between statin use and incidence of sepsis and sepsis-related mortality inconclusive. The clinical benefit of statin therapy in sepsis remains to be determined. CONCLUSIONS: There is an association between statin use and a lower incidence of sepsis and sepsis-related mortality. However, a causal relationship between statin use and reduced sepsis-related mortality has not yet been established. Currently, statins cannot be recommended for sepsis prevention or treatment until controlled trials are performed.