new chemical entity development, to programs
consisting of little more than a single study.
What influences the basic size and expense for
a proposed Rx-to-OTC switch is whether or not
either the indication or the dose of the drug will
change.
New indication or dose size
If the indication or the dose is to be changed, you
will be involved with an entirely new IND/NDA,
which is needed to show the fundamental efficacy
and safety of the drug, either at its new dose or in
its new indication. Such a program obviously
will require several years and involve extensive
expenditure.
Same indication and dose size:
actual use studies
In contrast to this are the programs of modest size
often required for the switch of drugs that will be
taken into the OTC market at their existing pre-
scription dosage and for their existing prescription
indications. Here, the regulatory agencies will gen-
erally accept the concept that there is no need to
prove again the basic safety and efficacy of the
drug, because this has already been done in the
primary new chemical entity NDA. Such a repeti-
tion would not provide useful new data. What will
be required is an actual use study, to show that the
proposed labeling for OTC use is effective in
enabling patients to use the drug properly. Also,
it may be necessary to address whatever specific
factor it is that has been obstructing the drug from
OTC use hitherto.
For example, if there is a question as to whether
the prescription indication that will now be taken
OTC is self-diagnosable, then a study of self-diag-
nosis will be required. This occurred with the
vaginal antifungal compounds, which were long
kept on prescription status because of questions as
towhether women could effectively diagnose vagi-
nalcandidiasis themselves. Only asingle study was
required to resolve this issue. It was extremely
unusual for the pharmaceutical industry, in that it
involved no drugs of anykind. It was simply a study
of women’s ability to self-diagnose, but it resolved
the one outstanding issue that had blocked OTC
approval.
The time required to carry out studies on such
special questions canvary, considerably depending
on the complexity of the question. However, it is
typically a brief program and its budget is com-
monlysmall by thestandards of thepharmaceutical
industry. It is obvious that in the planning and
preparation of a switch program, it is essential
not to assume that a full safety and efficacy pro-
gram will be required. Rather, early communica-
tion with the regulatory agencies is needed in order
to establish what barriers actually exist.14.5 Special study designs
for the OTC areaThe philosophy for OTC study design is signifi-
cantly different from that of prescription medica-
tion studies. With prescription medications, you
are typically striving to answer the basic scientific
questions of ‘can this drug work effectively’? and
‘is it safe to administer to people’? Therefore, it is
appropriate to study these new chemical entities
primarily in highly controlled settings with exten-
sive inclusion and exclusion criteria. This provides
increased safety for the studyparticipants, whowill
be using a drug of relatively unknown toxicity.
Also, it allows a reduction in the inherent variabil-
ity of the study population so as to obtain a clearer
scientific answer to the questions of basic safety
and efficacy. Every effort is made in studies of
this type to control for all possible variables and
to reduce random real-world circumstances to a
minimum.
For drugs being prepared for the self-medication
market, it is just the opposite. In this situation, a
great deal of evidence is already available about the
safety and efficacy of the drug. The key issue is
whether the drug can work in the real-world con-
text, with all the inherent happenstance and ran-
domness in an environment that is relatively more
chaotic than even outpatient IND/CTA studies.
Realism is the key to OTC research design.14.5 SPECIAL STUDY DESIGNS FOR THE OTC AREA 187