peripheral control of national affiliates. There are
many determinants of the balance between the
two. However, if a corporate culture is dissonant
with the societal and medical cultural imperatives
of a subsidiary or affiliate organization, yet is
imposed upon that organization because of a pol-
icy of ‘centralization’, then a suboptimal outcome
is likely. Conversely, a strong, responsive corporate
culture that is consonant with local societal and
medical values increases the likelihood of success.
A locally responsive corporate culture favors
neither centralization nor decentralization – this
will depend on many other considerations (e.g.
size of operations, in-country management capabil-
ity, etc.). However, it facilitates an appropriate
devolution of managerial power, which might
otherwise be difficult or even impossible. The chal-
lenge to the multinational corporation, therefore, is
to have a strong corporate culture that is compatible
with diverse societal and medical cultures.
50.2 The legal/regulatory
framework for drug
development in Europe
and the United StatesThe International Conference on Harmonization
(ICH) documentGeneral Considerations for Clin-
ical Trials, seeks to do the following:
Describe the internationally accepted principles
and practices in the conduct of both individual
clinical trials and the overall development strat-
egy for new medicinal products.
Facilitate the evaluation and acceptance of for-
eign clinical trial data by promoting common
understanding of general principles and
approaches, and also the definition of relevant
terms.
Present an overview of the ICH clinical safety
and efficacy documents and facilitate the user’s
access to guidance pertinent to clinical trials
within these documents.
In Western Europe, in spite of the Clinical Trials
Directive, there is still no uniformity in the order of
approval/submission of documentation by the var-
ious parties involved. For example, although all
countries now require review and approval of
phase I clinical protocols, in some countries,
approval of a study by the local or national ethics
committee is required before documentation is
submitted to the competent national authorities,
whereas in others, this order is reversed. The doc-
umentation that is required to be submitted to the
authorities is also quitevariable (Table 50.2). Some
countries require brief summaries of available
information, whereas others require detailed infor-
mation on the preclinical, pharmacy, chemistry and
other clinical data to be submitted.
All European countries require, in common with
the United States, and in conformity with the
Declaration of Helsinki, that ethics committees
(the European version of institutional review
boards in the United States) review protocols
from phase I–IV and the general conduct of trials
outside the formal protocol document. However,
there is wide variation in Europe as to how this
procedure is enacted. In countries such as France,
Spain and Germany, there is a national system of
ethics committees that duplicate similar work at a
local level. In the United Kingdom, there are awide
variety of ethics committees, such as commercial
committees, those set up by the Royal College of
Physicians, and those run by local area health
authorities or hospital trusts.
Local medical and societal cultural factors
impact on the ethics committee approvals, so that
a study that is considered to be ethical in one
country may be regarded as unethical in another.
Examples of this may be the unacceptability of the
use of placebo control in depression studies in
Germany, whereas similar studies would be per-
mitted elsewhere. Similarly, the common practice
of extensive blood sampling in Belgium, especially
in pediatric studies, would be regarded as excessive
and hence unethical in other countries.
In the Central and Eastern Region (CEE) of
Europe, the clinical trials approval system con-
tinues to evolve rapidly. In general, the regulations
are converging towards the EU model of submis-
sion and approval, but local practices make648 CH50 THE MULTINATIONAL CORPORATIONS