DELTA2 guidance on choosing the target difference and undertaking and reporting the sample size calculation for a randomised controlled trial.

The randomised controlled trial (RCT) is considered the gold standard to assess comparative clinical efficacy and effectiveness and can be a key source of data for estimating costeffectiveness. Central to the design of a RCT is an a-priori sample size calculation which ensures the study has a high probability of achieving its pre-specified main objective. Beyond pure statistical or scientific concerns, it is ethically imperative that an appropriate number of study participants be recruited, to avoid imposing the burdens of a clinical trial on more patients than necessary. The scientific concern is satisfied and the ethical imperative further addressed by specifying a target difference between treatments that is considered realistic and/or important by one or more key stakeholder groups. The sample size calculation ensures that the trial will have the required statistical power to identify whether a difference of a particular magnitude exists. The key messages from the DELTA2 guidance on determining the target difference and sample size calculation for a RCT are presented. Recommendations for the subsequent reporting of the sample size calculation are also provided.This project was funded by the MRC-NIHR Methodology Research Programme in the UK in response to a commissioned call to lead a workshop on this topic in order to produce guidance