The prevalence of underpowered randomized clinical trials in rheumatology.

OBJECTIVE

The conduct of underpowered randomized controlled trials (RCT) has recently been criticized in medical journals. We investigated the current prevalence of underpowered RCT in rheumatology.

METHODS

We searched to identify randomized, prospective RCT assessing clinical efficacy of treatments for adult rheumatic diseases published in English in 2001 and 2002. RCT were assessed as positive or negative based on the result of the primary outcome measure. For phase III RCT with negative results without power analysis, we calculated adequate sample size using beta = 0.20 and alpha = 0.05. We also examined trial quality by assessing the adequacy of reported random sequence generation, allocation concealment, and analysis, and compared the quality of reporting of RCT with adequate and inadequate sample size.

RESULTS

A total of 228 RCT met inclusion criteria; of the 205 phase III trials, 119 were positive, 81 were negative. The remaining 5 trials made no statistical comparison between interventions, and did not supply enough information for a result to be calculated. Of the 86 negative or indeterminate RCT, 37 reported sample size calculations (all but 4 had adequate power). Of the 49 remaining phase III trials that did not report power calculations, we conducted sample size calculations; only 10 were adequately powered. Few of the underpowered RCT studied rare rheumatic diseases. Negative RCT with inadequate sample size were less likely to describe adequate random sequence generation or allocation concealment than positive RCT or negative RCT with adequate sample size.

CONCLUSION

The conduct of underpowered trials is not an infrequent occurrence in rheumatology, with only 50% of negative or indeterminate phase III rheumatology RCT in 2001-2002 having adequate sample size.