This role is greater in scope and responsibility in
the OTC area and everything must be done with
greater speed.
14.4 Prescription-to-OTC switch
One of the most dynamic areas in the pharmaceu-
tical industry today is the prescription-to-OTC
switch, commonly called theRx-to-OTC switch.
This is the process by which a drug that has pre-
viously been used only by prescription is converted
to self-medication status. We have already consid-
ered the criteria for OTC use of medications and
these criteria represent a sound guide in determin-
ing what drugs are suitable for switching. There are
no hard and fast guidelines for determining which
drugs may become suitable for OTC switch, but a
consideration of self-diagnosability of the disease
state to be treated, the general safety and tolerabil-
ity of the drug, its ability to show efficacy in the
hands of nonprofessionals and a relative absence of
problems with masking of symptoms all contribute
to making a drug more OTC-able.
The first question that arises when considering
the possibility of an OTC switch is, why has the
drug not been available OTC before and what can
be done to remove the obstruction? It is possible
that a drug may simply not have had adequate
prescription experience in the past. It takes time
to accumulate a substantial use database of real-
world experience. This is essential to make it pos-
sible to form a judgment about safety in prescrip-
tion use and, therefore, projected safety in OTC
use. What constitutes substantial use is always a
relative matter. Typically, at least three years of
data accumulation with a widely marketed drug is
required to be able to feel some security in making
judgments from the adverse reaction database
accumulated. For drugs with 1000 sales this can
easily take 10 years or more. The fewer problems
this database reveals, the better the drug will be as a
switch candidate.
It is sometimes possible to accelerate the accu-
mulation of data for a promising OTC candidate by
specialized phase IV studies. These studies accel-
erate the process of data collection by conducting
what amounts to a survey amongst clinicians using
the drug on a prescription basis. As the sole interest
is the gathering of adverse reaction data, with
special emphasis on rare and serious events, record
forms are kept very minimal, often to a single page.
The study design consists simply of a survey done
without control groups. Hundreds of clinicians, or
even thousands, must be contacted to participate in
the survey by submitting brief record forms on
patients they treat in their usual manner with the
prescription drug. Such a survey can rapidly pro-
vide a much more reliable database than sponta-
neous reporting. With a survey, you get both a
frequency of the various side effects and a reason-
able estimate of the number of patients treated,
which permits the calculation of accurate rates
for the adverse effects observed. This is in marked
contrast to the data obtained from an entirely spon-
taneous adverse reaction database, where it is
impossible to determine what the efficiency of
reporting is. Therefore, it is extremely difficult to
estimate correct rates of occurrence of individual
adverse effects. The spontaneous databases are
more useful for the qualitative evaluation of what
can happen with a drug than for the quantitative
evaluation of its true frequency. This type of
adverse reaction survey study can pave the way
for a switch effort in much less time than needed if
reliance is placed solely on spontaneous reports for
collection of data.
If the principal barrier to switch has been a lack
of clinical experience with a drug, this can be
remedied by the collection of a large adverse reac-
tion database. Once this is done, it is usually
straightforward to establish that the drug is safe
in prescription use. This is a major advance on the
road to OTC approval, but it certainly does not yet
prove that the drug will be safe and effective in the
hands of consumers without the benefit of a learned
intermediary. In order to establish this additional
point, it is almost always necessary to supplement
the analysis of adverse reaction databases with
clinical studies in realistic conditions, using the
labeling composed for the OTC product. We will
discuss the peculiar aspects of the design of clinical
studies suitable for such purposes later, but for now,
it is sufficient to note that they may usually proceed
with the objectives of establishing efficacy and side
effectsin a fully realistic OTC setting.14.4 PRESCRIPTION-TO-OTC SWITCH 185