Chemistry, manufacturing process and control
data
Pharmacology and toxicology data
Previous human experience (if any)
Additional information
Unlike in Europe, the US IND generally requires
the submission of full-length study reports whether
of clinical or preclinical studies, together with
relevant summaries to guide the reviewer through
the document. Although the writing involved in the
preparation of an IND may be regarded as onerous,
because the FDA reviewing staff views the 1571
form as a totality, its preparation should not be
regarded as a routine exercise. Rather, it should
be an occasion for a critical internal appraisal of the
data available and how they support the proposed
protocol. Clearly, this is how the FDA views the
document. The FDA peer review is thus not just an
administrative hurdle to be jumped but also is often
a useful, confidential third-party review of the drug
development program, and once studies have
received IND approval, further protocols can be
added with little trouble. Of course, the IND lays
down responsibilities for sponsors, which include
minimum reporting times for adverse events and
completion of qualification forms for investigators,
and so on. These steps add to the administrative
load of the clinical drug development process. It is
generally thought that it would be a bold company
that submitted a NDA to the FDA without the
FDA’s prior involvement via an IND. However,
this has been done successfully in the past and
will probably occur again.
A very important cultural difference between
Europe and the United States, that impacts on
drug development, is indirectly expressed at the
stage when the regulatory authority examines
the final submitted dossier. In the United States,
the FDA adopts a bottom-up stance, in which it
looks at the basic raw data and sees what conclu-
sions can be drawn from it, using its own criteria for
analysis and interpretation. In Europe, the autho-
rities tend to take the opposite approach: they look
at the conclusions of all the studies, as manifested
in the proposed labeling, patient leaflets and sum-
mary of product information, and examining to
what extent the data presented justify those con-
clusions. In Europe, considerable importance is
placed on the role of independent experts, whose
critical reports on the various sections of the dos-
sier provide a sort ofvade mecumfor the reviewer.
It is vitally important to understand in detail that
the expert report required in Europe is not the same
as the integrated summary required by the FDA.
In drug development, therefore, significant dif-
ferences exist on a country-by-country basis in
Europe as well as, to a far lesser extent, on a
state-by-state basis in the United States. These
differences manifest themselves not only in the
legal/regulatory framework but also in the com-
mercial practices that surround the conduct of clin-
ical trials by licensed medical practitioners.50.3 The medico-commercial
environment in the United
States and EuropeOne of the major differences between the United
States and Europe, as regards the conduct of
clinical trials, is the financing of medical care in
the two regions. Throughout Europe, medical care
is largely funded by governments. In the United
States, with some exceptions such as the State of
California and in the case of military veterans
nationwide, medical care is largely funded through
private insurance, generally paid by a person’s
employer. Coverage for many of those less able
to pay, such as the indigent and the elderly, is
provided by the government through the Medicare
and Medicaid programs. Military veterans are eli-
gible for medical treatment through the VA pro-
gram. For patients without ready access to medical
care, participation in a clinical trial may provide
needed medical care.
CROs and site management organizations
(SMOs) are organizations that run clinical trials,
using physicians who are full-time, part-time
or contract employees. The companies employ
regulatory staff, for IRB filing, adverse event noti-
fication and so on, as well as site coordinators,650 CH50 THE MULTINATIONAL CORPORATIONS