Ethnic Factors in New Drug Evaluations: Pharmacokinetic and Pharmacodynamic Considerations

Abstract

In recent years, there have been substantial efforts on the part of the International Conference on Harmonization (ICH) to provide guidance and/or guidelines to facilitate the registration of new drug and biologic products in the ICH regions. The objectives of these initiatives are to generate regulatory and developmental strategies that will assist in the use of a common database with limited bridging studies, when necessary, for demonstration of safety and efficacy of drugs among different ICH regions, thereby reducing regulatory burdens and promoting international harmonization of regulatory requirements.

Under the auspices of ICH, the United States Food and Drug Administration recently published a draft guideline entitled “Ethnic Factors in the Acceptability of Foreign Clinical Data.” The draft guideline classifies the various ethnic or racial factors that may account for the observed differences in response to certain drugs and delineates the possible use of supplemental or bridging studies to support the extrapolation of foreign clinical data to a new region. The bridging data may be derived from clinical trials, pharmacokinetic/pharmacodynamic studies, and/or dose-response studies, depending on the characteristics of the candidate drug, the environmental and cultural differences between regions, and the type of clinical data available in the drug application. Consideration of pharmacokinetic and/or pharmacodynamic data, in particular, is important in the selection of dosage regimen as well as in the evaluation of safety and efficacy of the drug. The understanding of the pharmacokinetic/pharmacodynamic relationship, if available, will further provide useful information on the shape of the dose-response (or concentration-response) curve and facilitate a rational determination of dosage regimen while maintaining the safety and efficacy profile of the drug in the population of the new region.