Necessity and requirements of bridging studies and their present status in Japan.

Abstract

The mainstays of the harmonized final document about ethnic factors in the acceptability of foreign clinical data include a complete clinical data package and a bridging study (for efficacy and/or for safety). A clinical data package that meets all of the regional regulatory requirements is defined as a complete clinical data package for submission and potential approval, irrespective of its geographic origin. The acceptability of the foreign clinical data component of the complete data package depends upon whether it can be extrapolated or employed as a bridge to the population of the new region. Ethnic factors can be defined as the intrinsic characteristics of recipients of a medicine, and extrinsic characteristics associated with the environment and culture in which the subjects reside. Based on retrospective studies, inter-ethnic differences in ADME seem to be not greater than intra-ethnic variations for most medicines, and extrinsic factors appear to be more important than intrinsic factors for the assessment of efficacy and safety of the drug across ethnicity. Medical practice may represent one of the biggest differences and may perhaps prove to be very difficult to provide a harmonization for these extrinsic factors. The bridging study concept has primarily been brought up to overcome the difficulties inherent to extrinsic factors caused by different ethnicity. In Japan, the clinical trials advice division of the organization for pharmaceutical safety and research (OPSR) has been dealing with consultations about bridging studies since February 1998. The contents of consultations can be classified into 5 types. The most common type involves the desire by industries to bridge or extrapolate the results of foreign, phase III, clinical studies by conducting the dose-response studies domestically in the form of bridging studies. Until we have more information and have collected experiences in the variations caused by the regional differences as a result of extrinsic as well as intrinsic ethnic factors, we hope and believe that this document will serve to help provide great advancements in the acceptance of foreign clinical data.