Understanding power in randomized trials: The example of vertebroplasty

Objectives: Randomized trials (RCTs) should include a sufficient number of patients to reduce the risk that the observed outcome is a result of chance rather than from a truly different treatment effect. Trials must be even larger to claim an absence of treatment effect in a placebo-controlled trial. To estimate the size of the trial and maximize power, it is often suggested to use a comparison between the means of a continuous variable.

Methods: We examine the RCTs that have compared vertebroplasty and placebo for patients with osteoporotic fractures. Most trials compared the means of a continuous pain score to yield implausibly small trials, as small as 24 patients per group.

Results: The minimally significant difference between groups has no precise clinical meaning for patients when it is based on a comparison of means of pain scores. A comparison of the proportions of patients reaching a per-patient outcome measure of treatment success is much more pertinent if the trial is to inform the care of future patients. The resulting trials will admittedly need to be larger, but they will be much less likely to fall prey to the 'evidence of absence' fallacy. Furthermore, trial size should also take into consideration harder clinical outcome measures, such as death and disability.

Conclusion: When the goal of a trial is to inform outcome-based medical care, comparing the proportions of patients reaching a clinically pertinent outcome is more appropriate than comparing the means of a continuous variable.