if not useful, are soon discarded (Benet, 1992).
Despite the presence of multiple conflicting fac-
tors, the global dosage trend is toward a global
‘mean’. Over time, the same dosage range
emerges in many countries, adjusting to the
‘real world’ as opposed to the narrow demo-
graphics of research or cultural expectations.Generally, where dosages are the same, the inci-
dence ofseriousadverse events tends to be the
same in the three regions (Edwards, 1993;
Papaluca, 1993).
Objective differences, when found, are largely
due to physiologic influences (blood/body
volume and metabolic intrapopulation differ-
ences) and less commonly due to ethnic varia-
tion. In the United States, an estimate of less than
5% of drugs subject to significant clinical ethnic
variation was reported by participating compa-
nies in a USA/PMA Survey (Edwards, 1991) and
confirmed by the retrospective surveys under-
taken forICH 2 (Harveyand Walker, 1993;Natio
and Yasuhova, 1993).
Data are more interchangeable between the
United States and Europe than between Japan
and the United States, or between Japan and
Europe, but this is less often due to PK differ-
ences, body size and diet but more often to the
even larger differences in medical and cultural
attitudes of Japan, Europe and the United States
which influence dose selection and data compat-
ibility.
18.6 The future
Technology, television, transcontinental travel and
international scientific and medical conferences
continue to narrow the subjective variations. Dif-
ferences in diagnosis, data measurement and inter-
pretation will diminish with such exchanges. It is
possible that methodology, study design and case
report forms can be constructed that correct for
culture, diet and at least some subjective factors,
which will allow comparability of efficacy and
adverse events on dose/mg/kg body weight mea-
sured between European, US and Japanese data.
In conclusion, most but not all differences will
disappear and indeed, from such diversity, there
may spring new understanding of both clinical and
therapeutic mechanisms for the development and
applicability of better medications.Recommended further reading
Walker S, Lumley C, McAuslane N (1994)The
Relevance of Ethnic Factors in the Clinical Eva-
luation of Medicines. Kluwer Academic:
Hingham, MA.
Federal Register (1999) Ethnic factors in the
acceptability of foreign clinical data.Federal
Register63(111), June 10: 31790–94.
Payer L. 1988. Medicive and Culture H. Holt
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