Extension of a conditional performance score for sample size recalculation rules to the setting of binary endpoints

Abstract

Abstract Background Sample size calculation is a central aspect in planning of clinical trials. The sample size is calculated based on parameter assumptions, like the treatment effect and the endpoint’s variance. A fundamental problem of this approach is that the true distribution parameters are not known before the trial. Hence, sample size calculation always contains a certain degree of uncertainty, leading to the risk of underpowering or oversizing a trial. One way to cope with this uncertainty are adaptive designs. Adaptive designs allow to adjust the sample size during an interim analysis. There is a large number of such recalculation rules to choose from. To guide the choice of a suitable adaptive design with sample size recalculation, previous literature suggests a conditional performance score for studies with a normally distributed endpoint. However, binary endpoints are also frequently applied in clinical trials and the application of the conditional performance score to binary endpoints is not yet investigated. Methods We extend the theory of the conditional performance score to binary endpoints by suggesting a related one-dimensional score parametrization. We moreover perform a simulation study to evaluate the operational characteristics and to illustrate application. Results We find that the score definition can be extended without modification to the case of binary endpoints. We represent the score results by a single distribution parameter, and therefore derive a single effect measure, which contains the difference in proportions $$p_{I}-p_{C}$$ p I - p C between the intervention and the control group, as well as the endpoint proportion $$p_{C}$$ p C in the control group. Conclusions This research extends the theory of the conditional performance score to binary endpoints and demonstrates its application in practice.

Keywords

• Adaptive designs
• Sample size recalculation
• Performance score
• Binary endpoint