The use of a registry database in clinical trial design: assessing the influence of entry criteria on statistical power and number of eligible patients.

Randomized clinical trials (RCTs) are prospective empirical studies used to investigate the effect of a particular medical intervention. The design of a clinical trial is a delicate decision process, as each of the decisions that are taken in this process influences the eventual result of the clinical trial. Despite the efforts that are put into trial design, many trials fail to show an effect of the intervention. In some of these situations the intervention may be truly ineffective, however, more often this is caused by problems with the inclusion of patients and a resulting lack of statistical power to show the effect. To avoid this problem, in the design of a trial, the statistical power that can be achieved with the current design choices is calculated and balanced with economic considerations. In the choice of the entry criteria however, an important step in the design process, the influence of the chosen criteria on statistical power and number of eligible patients is not quantified. As these criteria influence the characteristics of the study population and the number of patients that will be eligible for the trial, and thereby the chances of finding an effect of the intervention, we believe that also in the choice of entry criteria explicit estimates of the number of eligible patients should be made. This paper presents a method to arrive at precise, objective estimates of statistical power and the number of eligible patients, using a registry database. Furthermore, we describe how this method is incorporated in the process of choosing entry criteria for a clinical trial. We illustrate the method with an example in the area of severe sepsis.