SERMs, ethnicity, and clinical trials: opportunities and challenges.

Selective estrogen receptor modulators (SERMs) are an exciting new class of pharmacotherapeutics that may have application in a wide variety of disease states. The science, both basic and clinical, that would guide the usage of these agents is in some respects at a relatively early developmental stage. Thus, the research community has an opportunity, before their use becomes widespread, to structure clinical trials such that the most complete profiles of benefits and risks are described. Tamoxifen is the SERM that has been most extensively studied and for which there are indications for both treatment and prevention of breast cancer based on trials involving more than 50,000 women. Despite this seemingly adequate sample size, an extremely important question remains unanswered--namely, whether there are ethnic differences in benefit and adverse effects of SERMs. It has generally been the case that new pharmacologic agents are tested in relatively small numbers of subjects, often only male, in North America and western Europe. While the populations are multi-ethnic, clinical trial subjects are most often not representative of the ethnic variability of these areas. Guidelines for usage of new drugs based on data from small, ethnically limited population groups are then generalized to other population groups, without consideration that differences in drug metabolism and/or responsiveness might exist.