Cultural differences: implications on drug therapy and global drug development

INTRODUCTORY REMARKS: Discussing the "inter-ethnicity" of kinetics and actions of drugs is fraught with terminology problems. It is, however, generally accepted that "ethnicity" covers the influences of factors genetically and culturally transmitted. The study of inter-ethnic variability in drug response addresses the problem of distinguishing variability factors that are common to one particular group of individuals from those which are not specifically shared.

It is well known that for a number of drugs, the daily dose prescribed in Japan is lower than in the US and Europe. Presently, independent surveys strongly indicate that for a majority of drugs dose differences are not the result of pharmacokinetic differences. In addition, they indicate that inter-ethnic differences do not seem to be larger than intra-ethnic variations. The differences observed for daily doses must thus be found elsewhere than in pharmacogenetic traits.

The most important impediments encountered in the evaluation of minority patients include differences with respect to language, communication style, cultural belief. The same problems arise if studies performed in different geographic areas are compared, socio-economic aspects play then an even greater role. Language problems arise differently if minorities are evaluated and compared to a majority of patients living in the same country or if clinical studies are performed in different regions. Communication styles also differ markedly between cultures. As an example, certain gestures may be considered as disrespectful or insulting by some ethnic groups and constitute normal behavior in others.

Ethnicity clearly plays a role on the cross-cultural use of rating scales. Sophisticated rating scales established and validated in Western culture must undergo culturally sensitive revision and rigorous evaluation before their use in non-Western culture. EFFICACY-SAFETY ASSESSMENT: As an example, the assessment of risk and benefit is different in Japan, Europe and the United States. In Japan, safety is given a greater weighting relative to efficacy than in the two other regions. PLACEBO/NOCEBO EFFECTS: Placebo and nocebo effects are difficult to study, even in the absence of any cultural difference. They are even more so if ethnicity is concerned.

Clinicians treating cross-cultural patients must carefully explore the beliefs held by their patient regarding illness causality and treatment expectations.

There are many unanswered questions in the field of inter-ethnic variability in drug response. The present overview will not pretend to have given specific answers, but it is hoped that it will point to some areas where more research is needed, in particular in the area of methodologies to take inter-ethnicity into account during drug development.