A bridging study is defined as a supplemental study performed in a new region to provide pharmacodynamic or clinical data on efficacy, safety, dosage, and dose regimen in a new region that will allow extrapolation of the foreign clinical data to the new region. A drug believed to be ﾒinsensitive to ethnic factorsﾓ has characteristics that suggest minimal potential for clinically significant impact by ethnic factors on safety, efficacy or dose regimen. A drug that is ﾒsensitive to ethnic factorsﾓ has the potential for clinically significant impact by ethnic factors on safety, efficacy or dose response.

Ethnic factors may be classified as either extrinsic or intrinsic factors. Extrinsic ethnic factors are associated with environment and culture in which the person resides and tend to be less genetically and more culturally and behaviorally determined. In contrast, intrinsic ethnic factors define and identify a subpopulation. Examples include genetic polymorphism, age, gender, body surface area, and organ dysfunction. No one property of a drug is predictive of its relative sensitivity to ethnic factors. Some properties of a drug that make it less likely to be sensitive to ethnic factors include linear pharmacokinetics, flat pharmacodynamic curve for efficacy and safety, wide therapeutic dose range, high bioavailability, low potential for protein binding, nonsystemic mode of action, and minimal metabolism. Extrapolation of clinical data may be feasible without a bridging study if the drug is determined to be ethnically insensitive and extrinsic factors in the two regions are similar. Bridging studies may not be warranted when the drug is ethnically sensitive, but the regions are ethnically similar and there is sufficient clinical experience with the pharmacologically related drugs to provide reassurance that the class behaves similarly in the two regions with respect to efficacy, safety, dosage, and dose regimen. Bridging studies using pharmacologic endpoints may be warranted if the regions are ethnically dissimilar and the drug is ethnically sensitive but extrinsic factors are generally similar provided the drug class is familiar to the new region. In this situation, a pharmacodynamic study in the new region, using an endpoint that is thought to reflect relevant drug activity could be used. Controlled clinical trials in the new region would be needed if there are uncertainty about the selection of dose, little experience of controlled clinical trials performed in the foreign region, marked differences in medical practice, and unfamiliarity with the drug class in the new region.

The views expressed are the result of independent work and do not necessarily represent the views or findings of the United States Food and Drug Administration