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Critical Considerations in Drug Development in Ethnically Diverse Populations

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Abstract

In recent years, greater attention has been given to the detection of ethnic differences in drug response and the need to take these differences into account in drug development. Epidemiological studies have identified significant ethnic variations in the rate and pattern of certain diseases, such as cardiovascular diseases, and in the response to drug therapy. Racial or ethnic differences may be related to a number of factors, including social, environmental and genetic factors. Differences in genes or polymorphisms are common and represent major determinants of differences in the effects of medicines observed in various populations. Polymorphisms concern mainly drug metabolism enzymes, receptor proteins and hepatic metabolism. They may influence the pharmacokinetics and pharmacodynamics of a given compound. Although specific polymorphisms are not isolated to any particular ethnic group, polymorphism prevalence may vary between ethnic groups for various categories of medicines. Among drug classes that exhibit varying effects in ethnic groups, benzodiazepines, antidepressants, antipsychotics, analgesics, antihypertensives and antidiabetic agents have been studied. However, it remains unclear how to assess the impact of ethnic differences on drug development and registration.

In the E5 guidance from the International Conference on Harmonisation, the aim is “to permit the clinical data collected in one region to be used in the registration or approval of a drug or biological product in another region, while allowing for the influence of ethnic factors”. As a rule, approval of a new pharmaceutical product requires the demonstration of efficacy and safety by controlled clinical trials and the selection of an appropriate and safe dosage. The extrapolation of the original data collected in one region to another region depends of the similarity in dose response, efficacy and safety of the drug in both regions with or without dose adjustment. It is the responsibility of the sponsor to decide whether or not the data can be extrapolated or if additional bridging studies are needed. The type of bridging studies depends on the critical properties of the compound, the ethnic differences between the new and original regions and the requirements of the regulatory authority in the new region.

Advances have been made in recent years and clinicians should be aware of the insights gained into ethnic differences in order to improve clinical management of certain diseases in ethnic groups. Ethnic differences observed in clinical trials may justify the approval of a specific drug formulation for a specific ethnic group. Drug development plans should be adjusted according to these known differences and adjustments should be anticipated when possible through different forms of collaboration with regulatory authorities.

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Acknowledgements

We wish to thank Thierry Nebout, MD, FFPM, for his critical review of the manuscript and Delphine Lebrasseur for her contribution to this work. No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

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  1. Institut de Recherches Internationales SERVIER 6, Place des Pléiades, FR-92415, Courbevoie Cedex, France

    Vidal Benatar

  2. Hôpital Nord, Marseille, France

    Samuel Lévy

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  1. Vidal Benatar
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  2. Samuel Lévy
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Benatar, V., Lévy, S. Critical Considerations in Drug Development in Ethnically Diverse Populations. Int J Pharm Med 20, 311–316 (2006). https://doi.org/10.2165/00124363-200620050-00005

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