Consideration of trial design comparing RCT to single arm study when abundant patient level historical data are available
*Peter Lam, Boston Scientific 

Keywords: Bayesian Conditional Borrowing Strategy, Propensity Score Method

Developing trial designs in randomizing patients undergoing percutaneous coronary intervention (PCI) into short term Dual Anti-Platelet Therapy (DAPT) duration versus long term DAPT duration are challenging and may not be ethical in light of the recent data release showing 30 months of DAPT was superior than 12 months of DAPT with respect to major adverse coronary endpoints at the expense of slightly higher major bleeding rate. However, there is a clinical need to demonstrate a shorter DAPT duration may be of benefit for patients who are at high risk for bleeding undergoing PCI with a novel drug eluting stent. To minimize the number of patients who are high risk for bleeding exposed to the long DAPT duration, one design option is a RCT with an unequal allocation based on a Bayesian conditional borrowing strategy with multiple cutoffs incorporating the historical prior extracting the target patients from the DAPT database with the control arm. This would potentially decrease the sample size needed further in the control arm in the new trial. Another design option is a single arm study design compared to the historical control using propensity score quintile approach extracting the target patients from the DAPT database. This eliminates the need to expose any patients who are at high risk for bleeding to the long DAPT duration. The two design options will be compared in terms of sample size requirement, operating characteristics, and operating challenges in recruiting patients.