Disparity between statistical significance and clinical importance in published randomised controlled trials: a methodological study.

OBJECTIVES

We estimated the extent of the disparity between statistical significance and clinical importance in published randomised controlled trials (RCTs), and explored factors associated with this disparity.

DESIGN

A methodological study of trials published between 2018 and 2022 and indexed in PubMed was conducted. Primary reports of two-arm, phase three, superiority trials of human health interventions were included. Pharmacokinetic studies and pilot trials were excluded. The relationship between the specified delta value or minimum clinically important difference (as specified in the sample size calculation) and the effect size determined the clinical importance of the trial results. Studies where the clinical importance was at least possible, with no statistical significance, were classified as SS-CI+ disparity, and studies which were definitely not clinically important but statistically significant were classified as SS+CI- disparity. Factors associated with each type of disparity were explored at the study level using multinomial logistic regression.

RESULTS

500 trials were included. In 38.4% (n=192) of these, information was not available to classify clinical importance. Overall disparity was found in 63 of the remaining 308 studies, 20.5% (95% confidence interval (CI) 16.2% to 25.5%). SS+CI- disparity was 10.3% (15/145) (95% CI 6.1% to 16.8%) and SS-CI+ disparity was 29.5% (48/163) (95% CI 22.7% to 37.2%).Studies testing complementary or alternative medicines relative to drug trials were positively associated with SS+CI- disparity. Low journal impact factor, small sample size, unfunded or grant funding and failure to mention allocation concealment were positively associated with SS-CI+disparity.

CONCLUSIONS

In up to 20% of RCTs, there may be a disparity between statistical significance and clinical importance. Clinical importance of results should be taken into account in the interpretation of trial results, and trials should adhere stringently to reporting guidelines.