EDITORIALS When Is a Confirmatory Randomized Clinical Trial Needed?

Few clinical trials show important advantages for one therapy over another. When one does, a confirmatory trial will help decide whether the observation in the first trial was real. The need to replicate experimental results is fundamental in science. Systematic differences occur across clinical trials for a variety of reasons: differences in patient populations (geographically and over time), different patient referral patterns, differential ap-plication of entry criteria by investigators, and so on. Results vary across trials, just as they vary across patients within a trial, although intertrial variability is usually less than interpatient variability. If the differences among trials affect all treatment arms similarly, then treatment differences may be similar in dif-ferent trials, but trial settings may well interact with treatment. The need for replication suggests that the answer to the ques-tion in the title is "Always. " But carrying out a confirmator