10 Phase IV Drug Development:

Post-Marketing Studies

Lisa R. Johnson-Pratt

10.1 Objectives of the phase IV

clinical development

program

Phase IV studies (in some companies subdivided
into phases IV and V) are mostly conducted after
initial product approval (although, occasionally,
some may begin prior to product launch, with
the risk that the product is not approved on sche-
dule, but with the potential to gain a competitive
advantage).
The range of purposes of phase IV studies is
broader than earlier phases of drug development.
There is usually no need to provide pivotal evi-
dence of efficacy (unless a new, second indication
for the drug is sought). Table 10.1 summarizes the
typical goals and tactics of phase IV studies.
The phase IV studies in some companies are
carried out by the original development team that
also did phases II and III. Some companies view
this as desirable because these are the people with
that repository of information, for the entire history
of the drug, who can spot or remember small events
that might merit further study in phases IV and V.
Some of those people will enjoy following the drug
through its entire life cycle, and will be glad for that
opportunity. However, others are either unwilling

or unable to evolve from a more regulation-

oriented to a more market-oriented approach to

clinical trials, and when these are in the majority,

some companies will then set up a separate depart-

ment, and thus achieve an essentially phase-

oriented departmental structure.

Types of phase IV studies

The typical characteristics of phase IV studies, in

comparison with phases I, II and III, therefore are

that they are larger, less technically complicated,

have fewer inclusion/exclusion criteria and are

more likely to include subjective or qualitative

end points (e.g. quality of life or patient satisfac-

tion). Rigorous, placebo-controlled, parallel-group

studies still find a place, however, when a supple-

mental licence application for a new indication is

being investigated. As a particular marketplace

becomes more crowded, the competition for places

in formularies and for reimbursements increases,

and some phase IV studies are designed specifi-

cally to provide information for consumer and

healthcare delivery organizations, whether natio-

nalized or not; placebo-controlled studies are us-

ually inadequate for this purpose (unless the

product is unique). Table 10.2 summarizes some

Principles and Practice of Pharmaceutical Medicine, 2nd Edition Edited by L. D. Edwards, A. J. Fletcher, A. W. Fox and P. D. Stonier
#2007 John Wiley & Sons, Ltd ISBN: 978-0-470-09313-9