- Interaction Effects in Bridging Studies

Abstract

Although a drug has been approved by regulatory authorities to treat a certain disease or illness due to its overall effectiveness and safety, there may still exist a considerable variability of responses to the drug among different ethnic, geographic, genetic, and demographic factors of the patients. In particular, the International Conference on Harmonisation (ICH) E5 guideline “Ethnic Factors in the Acceptability of Foreign Clinical Data” addresses the issue of extensive duplication of clinical evaluation to address the geographic variation of ef‚cacy and safety of a drug product (ICH, 1998). Therefore, according to the ICH E5 guideline, the supplementary pharmacodynamic and clinical data on ef‚cacy, safety, dosage, and dose regimen from bridging studies conducted in the new region makes it possible for us to extrapolate the foreign clinical data to the population of the new region. In addition, the ICH E5 guideline suggests the use of the concept of similarity for evaluation of extrapolation of the foreign clinical data. Currently, different statistical procedures or methods are proposed to evaluate the similarity of the treatment effects obtained from the bridging studies in the new region and those from the original regions for the assessment of extrapolation of foreign clinical data (Chow, Shao, and Hu, 2002; Hsiao, Hsu, Tsou, and Liu, 2007; Hsiao,Xu, and Liu, 2003, 2005; Ko, 2010; Liu and Chow, 2002; Liu, Hsiao, and Hsueh, 2002; Liu, Hsueh, and Hsiao, 2004; Shih, 2001).