criteria for diagnosis, they may be as capable
of rendering the diagnosis as accurately as the
clinician.
Even when a fully adequate description of
symptoms and signs is not practicable for patient
labeling, this barrier may be surmounted by limit-
ing use to patients who have previously had the
condition and had been diagnosed by a profes-
sional. Once some diseases have been experienced,
they are unmistakable. This approach emphasizes
the need for the Sponsor to think creatively in
evaluating whether or not a disease can be made
self-diagnosable.
OTC products offer an opportunity for real and
very meaningful creativity in devising wording and
graphics that can explain a diagnosis in a way that
lay persons can effectively understand and use.
Usually, the best OTC labeling is obtained by an
iterative process in which various labeling possi-
bilities are tried out in label comprehension tests.
These nonclinical trials do not actually use the
drug but simply ask patients, preferably with the
disease of interest, read the proposed labeling and
then take a test to find out what they understood.
The results can be most illuminating and can guide
the sponsor far more effective ways of getting the
right message across.
Differential diagnosis
Once a condition is established as self-diagnosable,
a related consideration isthe differential diagnosis –
the potential consequence of confusing the disease
withothersimilarlypresentingones,possiblyresult-
ing in a major delay in treatment. This consideration
can often be a dominant factor in determining
whether a condition is safely self-treatable. In con-
ditionswhereminimalconsequencesarelikelyfrom
a misdiagnosis, a modest level of diagnostic inaccu-
racy is tolerable to obtain the benefits of self-
medication. If the major downside of misdiagnosis
is simply the persistence or modest worsening of
symptoms without serious health consequences,
even more difficult self-diagnoses may be reason-
able. However, itisusuallywise toplace a time limit
on the length of self-treatment without a satisfactory
response.
Drug safety
When evaluating the safety and tolerability of a
drug for possible OTC use, one must first consider
the quality of available information. Many drugs,
particularly those used for a long time as prescrip-
tion medications, have extensive safety databases.
However, some do not, especially older drugs that
predate modern research standards and newer
drugs with insufficient usage. Also, with some
drugs, the tolerability of one formulation may dif-
fer greatly from that of another. One example is
benzyl peroxide, in which formulations may vary
greatly, even at the same strength but with different
excipients. Where such problems mean that there is
an inadequate database for an intended OTC for-
mulation, clinical testing will be needed before
launch.
Safety is usually the controlling factor in deter-
mining suitability for OTC use, and involves sev-
eral factors:The ‘therapeutic window’ (or ‘therapeutic
index’, i.e. the size of the difference between
therapeutic and toxic doses). This varies widely
for both prescription and OTC drugs and is often
less of a safety determinant than might be sup-
posed.For example, theprescriptiondrug sucral-
fate for the treatment of ulcers has extremely low
toxicity, whereas OTC systemic decongestants
typically have a narrower therapeutic window
than have most prescription drugs, as has
recently been seen leading to restrictions on
ephedrine-containing products in the United
States and Europe.The effects and consequences of toxicity and
overdosage.The ease of recognition of early signs of toxicity
to allow reduction in dosage or professional
assistance.Safety (negative propensity to causegenuine harm)
can be distinguished from tolerability (negative
propensity to cause limited adverse effects). Toler-
ability can limit OTC use even when safety is good.
This is particularly true for topical agents such as14.2 CRITERIA FOR OTC USE OF MEDICINES 181