English to Russian Other Mathematics & Statistics

In response to proposed equivalence margins of ±13% (90% power with planned sample size of N=614 total), the Agency recommended (letter dated 08 April 2015) that the similarity margin for ACR20 response rates in the proposed CCS (comparative clinical study) in RA be set at ±12%, and that the type I error rate of a test of similarity be controlled at 1-sided 5%.

The Agency further noted that they would consider a proposal for a relaxed upper bound as part of an asymmetric similarity margin.

In response, we sought Agency’s comments on a proposed asymmetric margin of (-12%, +15%) for the similarity assessment in the CCS which was subsequently accepted. on Sept 15, 2015 along with a 90% CI for the difference in ACR 20 response rates at Week 14 to justify for the similarity assessment in B5371002 comparative clinical study.

The following subsections outline the justification for the proposed asymmetric margin.