Studies in Support of Special Populations

10. Ethnic Differences

Although ethnic differences among populations may cause differences in a medicine’s safety, efficacy, dosage or dose regimen, many medicines do have comparable characteristics and effects across regions. Extensive duplication of clinical evaluation for every compound can delay the availability of new therapies and unnecessarily waste medicines development resources.

Once a clinical data package fulfils the regulatory requirements of a new region, the only remaining issue with respect to the acceptance of the foreign clinical data is its ability to be extrapolated (projected) to the population of the new region.

The Regulatory Authority or the sponsor may be concerned that differences in ethnic factors could alter the efficacy or safety of the medicine in the population in the new region.  If this is the case, the sponsor may need to generate a limited amount of clinical data in the new region in order to extrapolate or ‘bridge’ the clinical data between the two regions.

Characterisation of a medicine according to the potential impact of ethnic factors upon its pharmacokinetics, pharmacodynamics and therapeutic effects may be useful in deciding what sort of bridging study is needed in the new region.

No single property of the medicine can be used to predict sensitivity to ethnic factors.  Furthermore, the impact of ethnic factors upon a medicine’s effect will vary depending upon:

  • Its pharmacologic class, e.g. the group of medicines it belongs to
  • Its indication, and
  • The age and gender of the patient.

The following properties of a compound make it more likely to be sensitive to ethnic factors:

  • Differences in time or dose can arise from factors associated with absorption, metabolism, binding, and excretion.
  • A steep pharmacodynamic curve for both efficacy and safety in the range of the recommended dose and dose regimen – i.e. a small change in dose results in a large change in effect.
  • A narrow therapeutic dose range i.e. there is not much of a gap between a potentially ‘safe and effective’ dose and a ‘toxic’ dose.
  • High metabolism, especially through a single pathway, thereby increasing the chance of interactions between medicines.
  • Genetic modifications causing slightly different versions of an enzyme, can affect this enzyme’s metabolism.
  • Administration as a pro-medicine (inactive medicine that is activated by metabolism), with the potential for differences in how it is converted across ethnic groups.
  • High variation between participants in ‘bioavailability’, i.e. the amount of  the dose of medicine that reaches the bloodstream.
  • Low bioavailability, so more prone to dietary absorption effects.
  • High likelihood of being used alongside multiple other medicines.
  • High likelihood for inappropriate use, e.g. analgesics and tranquilisers.