11.3.1 Non-inferiority margin estimation This study is powered for analysis of successful anticoagulation treatment and monitoring. For this calculation we have used data from studies on the clinical outcome of patients with mixed indications for anticoagulation, monitored and dosed by anticoagulation management centers (Palareti, Leali et al. 1996; Wilson, Wells et al. 2003; Abdelhafiz and Wheeldon 2004; Menendez-Jandula, Souto et al. 2005). In these studies the combined endpoints of major bleeding and thromboembolic events ranged from 2.7 to 7.3 per 100 patients years and event rate for thromboembolic events was 0.9 to 5.4 per 100 patient years (0.9-5.4%) with the lower margin of the 95% CI ranging form 2.9 to 8.2%. The largest observational study (Palareti, Leali et al. 1996; Wilson, Wells et al. 2003; Abdelhafiz and Wheeldon 2004; Menendez-Jandula, Souto et al. 2005) and the only randomized study (Palareti, Leali et al. 1996; Wilson, Wells et al. 2003; Abdelhafiz and Wheeldon 2004; Menendez-Jandula, Souto et al. 2005) had an TE event rate of 3.5 and 5.4% respectively. We therefore chose to use 3% TE-event rate as our expected TE-event rate (97% success rate) and the non-inferiority of 5.5% (94.5% success rate for efficacy). We consider this 2.5% difference one that is clinically significant, yet within the 95% CI for event rate in some prior studies. Based on these considerations, the appropriate number of participants needed to demonstrate statistical non-inferiority of clinically important events for the test method with an 80% certainty after one year of observation are about 600 (576) patients in each group, i.e. 600 (576) patient years in each group.