INADEQUATE SIZE OF NEGATIVE CLINICAL-TRIALS IN DERMATOLOGY

Fifty-eight clinical trials with negative conclusions, published in three British dermatological journals over the last 4 years, were reviewed to determine the risk of their having missed an effective treatment. All but one of the 44 evaluable trials had a greater than 1 in 10 risk of missing a 25% relative treatment difference (median risk 81%), and 31 of the trials (70%) were so small that they had a greater than 1 in 10 risk of missing a 50% relative treatment difference (median risk 42%). The 'negative' trial result was compatible (within 95% confidence limits) with a 25% beneficial relative treatment effect in 36 studies (82%), and a 50% treatment benefit in 22 studies (50%). Only one study used confidence intervals to describe the main findings, and only three studies (7%) mentioned the basis for sample size estimation at the outset of the study. Of particular concern was that in half (23/44) of the studies there was an incorrect interpretation of the findings. It is worrying to observe such a profusion of clinical trials in dermatology which are too small to answer the questions being posed, especially when this is coupled with misreporting of results. Apart from ethical concerns, many treatments compatible with a considerable treatment benefit may have been erroneously discarded as a result of such studies. We recommend the use of confidence intervals to summarize clinical trial findings, so that readers can quickly decide whether clinically important treatment effects are plausible.