Statistical assessment of biosimilarity based on the relative distance between follow-on biologics for binary endpoints

Abstract

A new three-arm parallel design was recently proposed to investigate the biosimilarity between a biological product and a reference product by using the relative distance. The purpose of this article is to extend their results to binary endpoints for three popular metrics: the risk difference, the log relative risk, and the log odds ratio. The relative distances based on the three metrics are defined, and corresponding test procedures are developed. The type I error rates and powers are investigated theoretically and empirically.

Statistical tests for biosimilarity based on relative distance between follow-on biologics for ordinal endpoints

“…For P b , we utilize method by Shin and Kang (2016) in which relative distances for binary endpoints are proposed as biosimilarity criterion. They take risk difference and log odds ratio as a component of relative distance.…”

“…In this Section, type I error rate and power are investigated based on both measures ∆ and log α. Shin and Kang (2016) derived power function for binary endpoints; however, we deal with ordinal endpoints. For predefined margin δ ∆ > 0, if z α < δ ∆ /(σ ∆ / √ n 1 ), then type I error rate at…”

“…Accordingly, numerous research to show biosimilarity in a statistical aspect has been conducted. In particular, Shin and Kang (2016) considered three-arm parallel design for binary endpoints. However, determining biosimilarity with ordinal endpoints has not been studied.…”

“…Various statistical tests to assess biosimilarity have been proposed (Chen et al, 2017;Shin and Kang, 2016;Lu et al, 2014;Zhang et al, 2014;Yang et al, 2012;Kang and Chow, 2013). Kang and Chow (2013) considered statistical tests based on the ratio estimator and linearization method in a three-arm parallel design to determine biosimilarity between reference drugs and test drugs for continuous endpoints.…”

“…Kang and Shin (2015) extended three-arm parallel design to (k + 1)-arm parallel design. Shin and Kang (2016) extended statistical test based on the ratio estimator for binary endpoints. For the binary endpoints, the risk difference, the log relative risk, and the log odds ratio were taken for the ratio estimator.…”