The Impact of Incorporating Clinical Relevance on the Feasibility of Clinical Trials

In the past, data from placebo-controlled trials have been analyzed to demonstrate only a statistically significant treatment difference. However, the most important drawback of this classical approach is that looking at the presence or absence of an effect ignores the issue of effect size (ie, clinical relevance). A statistically significant treatment effect gives only the information that the treatment difference is not zero but does not provide information about the clinical relevance. Therefore, this practice has been criticized by regulatory authorities and the use of point estimates and corresponding confidence intervals has been recommended assessing additionally whether the observed treatment effect is also of clinical relevance. In this article, we focus on the implications of different criteria of defining clinical relevance, and we illustrate the consequences for clinical trials in patients with chronic obstructive pulmonary disease when the St. George's Respiratory Questionnaire is used as a symptomatic clinical endpoint. In conclusion, we demonstrate that the point estimate to exceed an a priori-defined threshold is an adequate method for incorporating clinical relevance required in addition to statistical significance.