some interactions. Many PLA/NDAs will contain
studies of particular drug interactions that seem
relevant at the time, especially when combination
therapy is the norm, or when there are biochemical
predictions that a new drug will interact with older
therapies (e.g. cytochrome P450 isoenzyme find-
ingsin vitro). Pharmacokinetic studies are typi-
cally done at small scale. But, in addition, the
phase IV team might be asked to do a retrospective
case-controlled analysis of the existing clinical
trials database trawling for differences between
patients who were and were not on a particular
concomitant therapy.
The clinical–marketing interface
As mentioned, one purpose of a phase IV clinical
trial program is to gather new indications or infor-
mation that can lead to a competitive advantage.
Optimization of the clinical–legal interface is cri-
tical to ensure success. It is the marketing team that
is the keeper of the strategy, aware of the compe-
titive environment (both current and future compe-
titors; within and outside of the class of the drug
under development) and closest to the commercial
environment that the drug will have to compete in
(e.g. Formulary issues; pricing concerns). In order
to ensure that the product is commercially success-
ful, it is important for the clinical team to embrace
this information when developing a phase IV
clinical trial program. It is especially important
when entering a very competitive, highly devel-
oped market place (e.g. Diabetes or hypertension)
where there are multiple treatment options or a lack
of perceived difference between members of a
particular drug class. It is also important for new
classes when there will be a within-class competi-
tor launching within a short timeframe. In these
cases, the label may be similar, especially in the
United States where there has been a trend in recent
years to have drugs within the same class have
similar labeling verbiage (i.e. ‘class labeling’). In
the absence of ‘current’ labeling differences
between competitors, it is sometimes the robust-
ness of the phase IV clinical trial program that will
differentiate competitors, as it is seen as a harbin-
ger of future indications or positive data. These
programs also highlight to the scientific and com-
munity the ‘commitment’ that the company has to
the drug and the disease state.
For these reasons, it is critical that the clinical
and marketing teams collaborate extensively on
the phase IV development program, usually via a
standing commercialization team with representa-
tives from other functional areas that will provide
sound input into the program to increase its
chance of success (e.g. Regulatory and legal).
The marketing team should provide the commer-
cialization team with a clear understanding of the
market environment, including past promotional
behavior of key competitors, so that a robust needs
assessment can be formulated. Once the commer-
cial case has been made, the clinical teams should
provide a scientific risk assessment that includes
the likelihood of success of achieving the desired
outcome. If the ultimate goal of a given study is
for promotional purposes, it is helpful for the
marketing team to provide examples of how that
data are intended to be promoted to ensure that the
trial is designed to ultimately allow for those
promotional messages.
With the financial stakes so high, it is no longer
acceptable for clinical teams to view their roles as
purely scientific. Success for a product is no longer
dependent solely on approval of indications. In our
information-driven society, consumers of scientific
information are always looking for new informa-
tion to continue to support their use of a product.
Effective collaboration between clinical develop-
ment and marketing teams in the context of phase
IV trials can go a long way toward optimizing sales
of an effective drug.The clinical–legal interface
Concern about product liability can both decline
and increase as phase IV proceeds. If, on the one
hand, the sudden exposure of large numbers of
patients to a new drug (i.e. large in comparison
to those in the PLA/NDA) does not result in a flurry
of serious adverse events, nor any signal of a
qualitatively new type of adverse event, then
there is reassurance that the label is probably
doing its job properly.124 CH10 PHASE IV DRUG DEVELOPMENT: POST-MARKETING STUDIES