Memorandum
Department Of Health and
Human Services
Food and Drugs Administration
Center For
Drug Evaluation and Research
Division of Over-the-Counter Drug Products (HFD-560)
Date:
From: Charles J. Ganley, M.D.
Director, Division of Over-the-Counter Drug
Products (HFD-560)
Subject: Consumer Behavior Issues Related To
the Marketing of Mevacor OTC
To: Joint
Nonprescription Drug / Endocrinologic and Metabolic
Drugs Advisory Committee scheduled to meet on January 13 and 14, 2005
The
proposal to market Mevacor OTC raises many issues that are different from the
typical drug considered for OTC marketing.
Most OTC drug products are currently marketed to treat symptomatic
conditions for short periods of time.
The duration of therapy can vary from a single dose to use for up to
several months. For many of these
conditions, consumers can accurately identify the symptom and receive positive
feedback if the symptoms resolve after ingesting medication (e.g. an internal
analgesic relieves a headache or minor muscle pain).
The
proposal to make Mevacor OTC does not follow this paradigm. Elevated cholesterol is not associated with
symptoms. Before using Mevacor OTC, consumers will be required to make several judgments
regarding age, the level of LDL-cholesterol (LDL-C), risk factors for
cardiovascular disease and relative contraindications to appropriately select to
use the product (self-selection).
Regardless of whether they do this correctly or not, they will also have
to make decisions regarding continuation of therapy (de-selection). There is no positive feedback related to
symptomatic improvement. Positive
feedback will have to come from a lower LDL-C level, which will require
motivation on the part of the consumer to educate themselves and continue to
get cholesterol testing. Unlike other
OTC drug products, Mevacor OTC should be a chronic therapy with the duration of
use determined by the response to therapy and the development of relative contraindications
during use. This clearly puts a burden
on users unparalleled by any currently marketed OTC product. Any person choosing to use Mevacor OTC will
have to be highly motivated in order to use it according to labeled
instructions.
When
making a decision to allow OTC marketing of a drug product, consumer behavior
regarding self-selection and use of the product, without the benefit of a
health provider, becomes pivotal in the benefit/ risk assessment. To help understand the possible implications
of Mevacor 20 mg OTC, the sponsor has conducted an actual use study (The Custom
Study) and a label comprehension study.
These studies attempt to provide information on how consumers may use
Mevacor in the OTC setting. FDA review
staff analyzed the results of these studies and their reviews are included in
this background package. FDA will
present its analysis of these studies at the advisory committee.
Label Comprehension Study
Section
502 (c) of the Federal Food, Drug, and Cosmetic Act (the Act) requires that
nonprescription drug labeling be “in such terms as to render it likely to be
read and understood by the ordinary individual under customary conditions of
purchase and use” (21 U.S.C. 352 (c)). Regulations further require that
labeling “state the intended uses and results of the product; adequate
directions for proper use: and warnings against unsafe use, side effects, and
adverse reactions in such terms as to render them likely to be read and
understood by the ordinary individual, including individuals of low
comprehension, under customary conditions of purchase and use.” (21 CFR 330.10
(a)(4)(v)).
A
label comprehension study assists in the development of labels for OTC drug
products. They focus on specific
communication directives and use several different techniques to evaluate the
content and format of labels.
Participants may be asked direct questions regarding specific language
in a label or they may be presented with scenarios describing a situation and
are asked whether the medication is appropriate for the individual described in
the scenario. The label comprehension
studies are often conducted to assist in the development of a label to be used
in an actual use study. Based on prior
FDA experience, successful label comprehension results are not always
reflective of subsequent consumer behavior.
Consumers may understand the content of a label but may exhibit behavior
that is contrary to the labeled instructions because unforeseen factors
contribute to the decision to use the drug.
Failure of label comprehension studies to meet objectives, however,
raise concerns about the ability of the label to adequately communicate.
Actual Use Study
New
drugs and drugs previously available only via prescription continue to be
introduced into the OTC market, where consumers make decisions as to whether or
not the drug is appropriate for them to use (i.e. self-selection, de-selection). Actual use trials can provide information
about the ability of consumers to self-diagnose their medical condition
(appropriate self-selection) and use the product safely and effectively in
accordance with the information on the label and/or other information tools
without the assistance of a learned intermediary. This also includes the ability to stop the
medication (appropriate de-selection) should drug related
adverse events occur or if the drug fails to provide benefit. Because other factors other than label
comprehension influence consumer behavior, the actual use study can be a better
predictor of use if the drug becomes available OTC.
An
actual use study attempts to mimic the OTC retail setting but there are
limitations to the study designs because investigator interaction is necessary
to conduct the study. They are not
perfect in their predictive nature but they can be helpful in identifying
potential problems that could lead to poor outcomes for some individuals. In the course of the deliberations of the
Mevacor OTC application, the advisory committee members will need to determine
whether the success and failure rate for specific objectives in the actual use study
support the marketing of Mevacor OTC.
The Custom Study
The Custom study is fairly straight forward in its design
but is complicated by the presentation of various analyses. It is
important to understand the details of the study protocol (described in the FDA
and sponsor background material) and differentiate between the various
analyses, what each mean and what the implications of each may be in the real
world. In the presentation of material in the background packages and at the
meeting, the definitions of various analysis groups or endpoints should be
clear and unambiguous.
It
is important to recognize that it is difficult to achieve 100% success when it
comes to the correct use of a drug product in the OTC setting. In the
course of the discussions of the study, it will be important for the members to
consider the following:
·
How efficacious
is the drug likely to be for the individual patient?
·
What are the
risks of using the drug for the individual patient (when used according to
labeled directions or when label is misinterpreted)?
·
Are there certain
subgroups that warrant greater concern because of increased risk for adverse
events?
·
What is the
risk/benefit for an individual patient or a specific subpopulation of consumers
who might use the product?
·
What is an
acceptable threshold for success and failure for the various objectives in the
study?
·
For a population
who fails to correctly exclude themselves from using the product, can a
projected benefit override the failure of self selection?