Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment Request; Study of Clinical Efficacy Information in Professional Labeling and Direct-to-Consumer Print Advertisements for Prescription Drugs, 75477-75481 [2010-30385]
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Federal Register / Vol. 75, No. 232 / Friday, December 3, 2010 / Notices
TABLE 2—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1
No. of
recordkeepers
21 CFR Section
Annual frequency per
recordkeeper
Total annual
records
Hours per
recordkeeper
Total hours
516.141 ................................................................................
516.165 ................................................................................
30
10
2
2
60
20
0.5
1
30
20
Total ..............................................................................
........................
........................
........................
........................
50
1
There are no capital costs or operating and maintenance costs associated with this collection of information.
Dated: November 29, 2010.
Leslie Kux,
Acting Assistant Commissioner for Policy.
796–3792,
Elizabeth.Berbakos@fda.hhs.gov.
BILLING CODE 4160–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2010–N–0266]
Agency Information Collection
Activities; Submission for Office of
Management and Budget Review;
Comment Request; Study of Clinical
Efficacy Information in Professional
Labeling and Direct-to-Consumer Print
Advertisements for Prescription Drugs
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA) is announcing
that a proposed collection of
information has been submitted to the
Office of Management and Budget
(OMB) for review and clearance under
the Paperwork Reduction Act of 1995.
DATES: Fax written comments on the
collection of information by January 3,
2011.
ADDRESSES: To ensure that comments on
the information collection are received,
OMB recommends that written
comments be faxed to the Office of
Information and Regulatory Affairs,
OMB, Attn: FDA Desk Officer, FAX:
202–395–7285, or e-mailed to
oira_submission@omb.eop.gov. All
comments should be identified with the
OMB control number 0910-new and title
‘‘Study of Clinical Efficacy Information
in Professional Labeling and Direct-toConsumer (DTC) Print Advertisements
for Prescription Drugs.’’ Also include the
FDA docket number found in brackets
in the heading of this document.
FOR FURTHER INFORMATION CONTACT:
Elizabeth Berbakos, Office of
Information Management, Food and
Drug Administration, 1350 Piccard Dr.,
PI50–400B, Rockville, MD 20850, 301–
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SUMMARY:
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In
compliance with 44 U.S.C. 3507, FDA
has submitted the following proposed
collection of information to OMB for
review and clearance. Study of Clinical
Efficacy Information in Professional
Labeling and Direct-to-Consumer (DTC)
Print Advertisements for Prescription
Drug—(OMB Control Number 0910–
New)
Section 1701(a)(4) of the Public
Health Service Act (42 U.S.C.
300u(a)(4)) authorizes FDA to conduct
research relating to health information.
Section 903(b)(2)(c) of the Federal Food,
Drug, and Cosmetic Act (FD&C Act) (21
U.S.C. 393(b)(2)(c)) authorizes FDA to
conduct research relating to drugs and
other FDA-regulated products in
carrying out the provisions of the FD&C
Act.
FDA regulations require that an
advertisement that makes claims about
a prescription drug include a ‘‘fair
balance’’ of information about the
benefits and risks of the advertised
product, in terms of both content and
presentation (21 CFR 202.1(e)(5)(ii)). In
past research FDA has focused primarily
on the risk component of the riskbenefit ratio. In the interest of
thoroughly exploring the issue of fair
balance, however, the presentation of
effectiveness, or benefit, information is
equally important.
The FD&C Act requires that
manufacturers, packers, and distributors
(sponsors) who advertise prescription
human and animal drugs, including
biological products for humans, disclose
in advertisements certain information
about the advertised product’s uses and
risks.1 By its nature, the presentation of
this risk information is likely to evoke
active trade-offs by consumers, i.e.,
comparisons with the perceived risks of
not taking treatment, and comparisons
with the perceived benefits of taking a
SUPPLEMENTARY INFORMATION:
[FR Doc. 2010–30316 Filed 12–2–10; 8:45 am]
1 For prescription drugs and biologics, the FD&C
Act requires advertisements to contain ‘‘information
in brief summary relating to side effects,
contraindications, and effectiveness’’ (21 U.S.C.
352(n)).
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treatment.2 Since FDA has an interest in
fostering safe and proper use of
prescription drugs, an activity that
engages both risks and benefits, an indepth understanding of consumers’
processing of this information is central
to this regulatory task.
Research and guidance to sponsors on
how to present benefit and efficacy
information in prescription drug
advertisements is limited. For example,
‘‘benefit claims,’’ broadly defined,
appearing in advertisements are often
presented in general language that does
not inform patients of the likelihood of
efficacy and are often simply variants of
an ‘‘intended use’’ statement. In a
content analysis of DTC advertising,3
the researchers classified the
‘‘promotional techniques’’ used in the
advertisements. Emotional appeals were
observed in 67 percent of the ads while
vague and qualitative benefit
terminology was found in 87 percent of
the ads. Only 9 percent contained data.
For risk information, however, half the
advertisements used data to describe
side-effects, typically with lists of sideeffects that generally occurred
infrequently.
FDA regulations require that
prescription drug advertisements that
make (promotional) claims about a
product also include risk information in
a ‘‘balanced’’ manner (21 CFR
202.1(e)(5)(ii)), both in terms of the
content and presentation of the
information. This balance applies to
both the front (aka ‘‘display’’) page of an
advertisement, as well as the brief
summary page. However, beyond the
‘‘balance’’ requirement limited guidance
and research exists to direct or
encourage sponsors to present benefit
claims that are informative, specific,
and reflect clinical effectiveness data.
The purpose of this project is to: (1)
Understand how physicians process
clinical efficacy information and how
2 See Schwartz, L., S. Woloshin, W. Black, et al.,
‘‘The Role of Numeracy in Understanding the
Benefit of Screening Mammography,’’ Annals of
Internal Medicine, 127(11), 966–72, 1997.
3 Woloshin, S. and L. Schwartz, ‘‘Direct to
Consumer Advertisements for Prescription Drugs:
What Are Americans Being Told,’’ Lancet, 358,
1141–46, 2001.
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Federal Register / Vol. 75, No. 232 / Friday, December 3, 2010 / Notices
they interpret approved product label
information,4 (2) determine physician
preferences for alternative presentations
of clinical efficacy information in DTC
advertising, and (3) examine how
different presentations of clinical
efficacy information in DTC advertising
affect consumers’ perceptions of efficacy
and safety. Specifically, we are
interested in how physicians and
consumers make risk/benefit
assessments and particularly, how
consumers make such judgments in
response to variations in the efficacy
presentations in the ‘‘display’’ (first)
page of a DTC print ad. A particular
concern is whether certain presentations
cause consumers to form skewed
perceptions or unfounded risk/benefit
tradeoffs. Therefore, we will investigate
to what extent consumers, when
provided with efficacy information,
form perceptions that correspond with
clinically-based physicians’ assessments
of the benefits, risks, and benefit/risk
tradeoffs of the same drugs. These
studies will inform FDA’s thinking
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4 As part of this effort, a qualitative mental
models procedure was completed that helped us
determine how physicians think about the efficacy
of potential pharmaceutical options (OMB control
no. 0910–0649).
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regarding how manufacturers may
provide useful and non-misleading
efficacy information in DTC print
advertisements.
Design Overview
This study will be conducted in two
concurrent, independent parts. The first
part will involve 2,500 consumers in an
experimental examination of variations
of the display page of print DTC ads for
two fictitious drugs, closely
approximating existing drugs for
overactive bladder (OAB) and benign
prostatic hyperplasia (BPH). In the
second part, 600 general practitioners
will review and evaluate a fictitious
‘‘approved’’ label for the same
conditions. This design will allow us to
compare consumers’ perceptions of
efficacy with a more objective measure
of the true efficacy of the drug as
measured by physician perceptions of
clinical efficacy from labeling.
Consumer experiment. In this part of
the study, women who have been
diagnosed with or are at risk for OAB
(self-designated based on relevant
symptoms) will be recruited and will
view one version of a DTC ad for a drug
to treat OAB. Men who have been
diagnosed with or are at risk for BPH
(self-designated based on relevant
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symptoms) will be recruited and will
view one version of a DTC ad for a drug
to treat BPH. Although the two
conditions are somewhat specific to
gender (men can suffer from OAB but it
is much more prevalent in women), they
share many of the same symptoms and
characteristics. These medical
conditions afford us the ability to
maintain various realistic manipulations
of placebo level and type of claim, as
explained below. The graphical
elements and construction of the two
ads will be comparable yet still realistic.
Consumers will be randomly assigned
to see 1 of 12 DTC print ads within their
respective medical condition and will
answer questions about the effectiveness
and safety of the fictitious drug
advertised in them. These twelve
experimental conditions will be created
by examining three independent
variables in the following manner: Type
of claim (2 levels: Treatment,
prevention), placebo rate (3 levels: High,
low, none), and framing (2 levels:
Single, mixed). Please note that the
numbers describing efficacy seen in the
following table are for illustration only.
Actual numbers used will be
determined by pretesting.
BILLING CODE 4160–01–P
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We will investigate variations of
numerical presentation in two different
types of claims: treatment and
prevention. Treatment claims usually
involve symptoms that may be
alleviated by taking a given prescription
drug. This type of claim is directly
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observable and somewhat testable by
patients. If bothersome symptoms do
not go away, a patient can return to the
healthcare provider with this
information and pursue additional
options for treatment. In general, drugs
that treat symptoms typically show
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75479
substantial percentages of people who
experience relief.
Prevention claims are important but
due to their long-term nature,
potentially harder to communicate. A
drug that prevents a negative future
event may not alleviate any symptoms
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at all. Patients may feel no benefit from
the drug and must trust their healthcare
provider and the data, as much as they
can process it, that the drug is providing
a positive benefit for them. The nature
of these claims is such that the event
being prevented is relatively rare, and
thus the numbers used to describe them
are often very small. For example, a
cholesterol drug that reduces the risk of
heart attack from 3 out of 100 to 2 out
of 100 may not seem objectively large,
but has enormous consequences for
millions of people and the healthcare
system in general. We chose to test this
type of claim to determine whether
consumers are sensitive to the
magnitude of the benefit in these
clinically meaningful but objectively
small and usually asymptomatic
outcomes. While we will examine the
current issues in both treatment and
prevention claims, we do not intend to
make comparisons between the two.
The second variable of interest is
communication of a placebo rate. Three
levels will be examined. In addition to
testing a control condition with no
placebo information, we will utilize a
high and low placebo rate to better
understand if and how consumers use
placebo information. We see three
possibilities: (1) People use placebo
numbers correctly, such that the low
placebo group demonstrates higher
perceived efficacy than the high placebo
group; (2) people use the placebo
numbers as a peripheral cue to mean
‘‘science’’ so there are no differences
between high and low placebo groups
on perceived efficacy but both are
higher than the no placebo group; and
(3) people do not find the numbers
meaningful or cannot process them, so
the high and low groups do not differ
from one another and they do not differ
from the no placebo group. In an
attempt to make our claims as realistic
as possible, we will maintain fairly low
rates of prevention in the prevention
conditions. For this reason, in addition
to the 12 cells in the table previously
illustrated in this document, we will
also have an additional control cell in
which the effectiveness rates are quite
high—higher than could reasonably be
expected but high enough to be
objectively noticeable (e.g., risk of
bladder cancer on Drug X, 4/100; risk of
bladder cancer on placebo, 15/100).
This additional condition will provide
confidence that our research
manipulations are operating as we
expect.
Finally, we will examine the addition
of mixed framing to the traditional use
of a single positive frame in a DTC ad.
Mixed framing provides the number of
people who benefited and the number of
people who did not benefit, whereas
positive framing provides only the
number of people who benefited. Only
a few studies have actually measured
this mixed approach 5 although risk
communication guides recommend the
use of mixed framing to create more
accurate perceptions.6 Although a
completely balanced design would also
include a negative framing condition
(which would provide only the number
of people who did not benefit), we feel
it is unrealistic to create an ad that
would suggest, for example, that ‘‘Drug
X did not work for 70 percent of people
in clinical trials,’’ so we have chosen not
to include negative framing in our
investigation.
In this part of the project, we are most
interested in consumers’ perceived
efficacy and safety, which we can then
compare with ratings physicians will
provide based on the prescribing
information, described in the next
section. We will also ask consumers
questions to measure their accuracy
with regard to claims, their recall of the
information in the ad, and demographic
questions that may influence their
responses, such as knowledge about
their medical condition and their level
of numeracy.
Physician Study. Six hundred general
practitioners 7 will participate in an
Internet survey lasting no longer than 20
minutes. They will complete two tasks
during this time. In the first task, they
will evaluate a prescription drug label
(also known as the prescribing
information, written for healthcare
practitioners) for one of the two
fictitious drugs described in the
consumer study below. To provide a
match for the variations of information
in the DTC ads the consumers will
observe, physicians will be randomly
assigned to see prescribing information
that varies in terms of claim type,
placebo rates in clinical trials, and the
medical condition the drug treats (OAB
or BPH).
As part of this task, we will obtain
timing and sequence information on
which sections of the label physicians
examine. This will enable us to have a
deeper understanding of physicians’
processing of the prescribing
information. We are not aware of
existing literature on this topic.
Additionally, physicians will answer
questions about the efficacy and safety
of the drug and quantitative questions
about the benefit shown in the clinical
studies (as described in the label). These
questions have been designed such that
they can be reasonably compared with
the responses of consumers who will
answer the same questions after viewing
a corresponding DTC ad.
In the second task, physicians will see
four versions of a print DTC ad for a
fictitious product for high cholesterol
and will rank the ads in order of how
representative of the clinical data as the
physicians know it the ads are and how
useful they believe the ads would be for
their patients.8 The four versions will be
selected to mirror the versions of the
OAB/BPH drug that consumers will see
in the consumer experiment (i.e., low
placebo, frame).
Thus, this research will provide us
with a rich data set in order to address
several questions: (1) How physicians
process clinical efficacy information
and how they use approved product
label information, (2) how physicians’
interpretations of clinical efficacy
information relate to their preferences
for alternative DTC ad presentations,
and (3) which variations of information
in DTC ads bring consumers closer to or
farther away from the conclusions of the
physicians regarding the same drugs.
FDA estimates the burden of this
collection of information as follows:
The total respondent sample for this
data collection is 3,400. We estimate the
response burden to be 20 minutes in the
first part and 15 minutes in the second
part, for a burden of 906 hours.
In the Federal Register of June 16,
2010 (75 FR 34142), FDA published a
60-day notice requesting public
comment on the proposed collection of
information. No comments were
received on the paperwork burden.
FDA estimates the burden of this
collection of information as follows:
5 For a literature review, see Moxey, A., D.
O’Connell, P. McGettigan, et al., ‘‘Describing
Treatment Effects to Patients: How They Are
Expressed Makes a Difference,’’ Journal of General
Internal Medicine, 18, 948–959, 2003.
6 Fagerlin, A., P.A. Ubel, D.M. Smith, et al.,
‘‘Making Numbers Matter: Present and Future
Research in Risk Communication,’’ American
Journal of Health Behavior, 31, S47–S56, 2007;
Schwartz, L.M., S. Woloshin, H.G. Welch, ‘‘Risk
Communication in Clinical Practice: Putting Cancer
in Context,’’ Monograph of the National Cancer
Institute, 25, 124–133, 1999.
7 Including internists, general practitioners, and
family practitioners.
8 To reduce burden, the physician sample will be
split in this task, so that half of the physicians see
the four ad versions with treatment claims and the
other half see the four ad versions with prevention
claims. Type of claim is described in greater detail
in the consumer experiment section.
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TABLE 1—TOTAL ESTIMATED ANNUAL REPORTING BURDEN 1
Number of
respondents
21 CFR Section
Physician survey—pretest ...................................................
Physician survey—main study .............................................
Consumer experiment—pretest ...........................................
Consumer experiment—main study ....................................
Annual
frequency
per response
100
600
200
2,500
Total annual
responses
1
1
1
1
100
600
200
2,500
Total ..............................................................................
1 There
FOR FURTHER INFORMATION CONTACT:
Johnny Vilela, Office of Information
Management, Food and Drug
Administration, 1350 Piccard Dr., PI50–
400B, Rockville, MD 20850, 301–796–
7651, juanmanuel.vilela@fda.hhs.gov.
BILLING CODE 4160–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
[Docket No. FDA–2010–N–0597]
Agency Information Collection
Activities; Proposed Collection;
Comment Request; Index of Legally
Marketed Unapproved New Animal
Drugs for Minor Species
Food and Drug Administration,
HHS.
Notice.
The Food and Drug
Administration (FDA) is announcing an
opportunity for public comment on the
proposed collection of certain
information by the Agency. Under the
Paperwork Reduction Act of 1995 (the
PRA), Federal Agencies are required to
publish notice in the Federal Register
concerning each proposed collection of
information, including each proposed
extension of an existing collection of
information, and to allow 60 days for
public comment in response to the
notice. This notice solicits comments on
the burden hours associated with
indexing of legally marketed
unapproved new animal drugs for minor
species.
DATES: Submit either electronic or
written comments on the collection of
information by February 1, 2011.
ADDRESSES: Submit electronic
comments on the collection of
information to https://
www.regulations.gov. Submit written
comments on the collection of
information to the Division of Dockets
Management (HFA–305), Food and Drug
Administration, 5630 Fishers Lane, Rm.
1061, Rockville, MD 20852. All
comments should be identified with the
SUMMARY:
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Under the
PRA (44 U.S.C. 3501–3520), Federal
Agencies must obtain approval from the
Office of Management and Budget
(OMB) for each collection of
information they conduct or sponsor.
‘‘Collection of information’’ is defined in
44 U.S.C. 3502(3) and 5 CFR 1320.3(c)
and includes Agency requests or
requirements that members of the public
submit reports, keep records, or provide
information to a third party. Section
3506(c)(2)(A) of the PRA (44 U.S.C.
3506(c)(2)(A)) requires Federal Agencies
to provide a 60-day notice in the
Federal Register concerning each
proposed collection of information,
including each proposed extension of an
existing collection of information,
before submitting the collection to OMB
for approval. To comply with this
requirement, FDA is publishing notice
of the proposed collection of
information set forth in this document.
With respect to the following
collection of information, FDA invites
comments on these topics: (1) Whether
the proposed collection of information
is necessary for the proper performance
of FDA’s functions, including whether
the information will have practical
utility; (2) the accuracy of FDA’s
estimate of the burden of the proposed
collection of information, including the
validity of the methodology and
assumptions used; (3) ways to enhance
the quality, utility, and clarity of the
information to be collected; and (4)
ways to minimize the burden of the
collection of information on
respondents, including through the use
of automated collection techniques,
when appropriate, and other forms of
information technology.
SUPPLEMENTARY INFORMATION:
Food and Drug Administration
mstockstill on DSKH9S0YB1PROD with NOTICES
33
198
50
625
906
docket number found in brackets in the
heading of this document.
[FR Doc. 2010–30385 Filed 12–2–10; 8:45 am]
ACTION:
.33
.33
.25
.25
Total hours
are no capital costs or operating and maintenance costs associated with this collection of information.
Dated: November 30, 2010.
Leslie Kux,
Acting Assistant Commissioner for Policy.
AGENCY:
Hours per
response
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Index of Legally Marketed Unapproved
New Animal Drugs for Minor Species—
21 CFR Part 516 (OMB Control Number
0910–0620)—Extension
The Minor Use and Minor Species
Animal Health Act of 2004 (MUMS Act)
amended the Federal Food, Drug, and
Cosmetic Act (the FD&C Act) to
authorize FDA to establish new
regulatory procedures intended to make
more medications legally available to
veterinarians and animal owners for the
treatment of minor animal species
(species other than cattle, horses, swine,
chickens, turkeys, dogs, and cats), as
well as uncommon diseases in major
animal species.
The MUMS Act added three new
sections to the FD&C Act (sections 571,
572, and 573 (21 U.S.C. 360ccc, 360ccc–
1, and 360ccc–2, respectively)). The
final rule (72 FR 69108, December 6,
2007) implements section 572 of the
FD&C Act, which provides for an index
of legally marketed unapproved new
animal drugs for minor species.
Participation in any part of the MUMS
program is optional so the associated
paperwork only applies to those who
choose to participate. The final rule
specifies, among other things, the
criteria and procedures for requesting
eligibility for indexing and for
requesting addition to the index as well
as the annual reporting requirements for
index holders.
Under the new subpart C of part 516
(21 CFR part 516, subpart C), § 516.119
provides requirements for naming a
permanent-resident U.S. agent by
foreign drug companies, and § 516.121
provides for informational meetings
with FDA. Section 516.123 provides
requirements for requesting informal
conferences regarding agency
administrative actions and § 516.125
provides for investigational use of new
animal drugs intended for indexing.
Provisions for requesting a
determination of eligibility for indexing
can be found under § 516.129 and
provisions for subsequent requests for
addition to the index can be found
under § 516.145. A description of the
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]]>Agencies
[Federal Register Volume 75, Number 232 (Friday, December 3, 2010)]
[Notices]
[Pages 75477-75481]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2010-30385]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2010-N-0266]
Agency Information Collection Activities; Submission for Office
of Management and Budget Review; Comment Request; Study of Clinical
Efficacy Information in Professional Labeling and Direct-to-Consumer
Print Advertisements for Prescription Drugs
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is announcing that a
proposed collection of information has been submitted to the Office of
Management and Budget (OMB) for review and clearance under the
Paperwork Reduction Act of 1995.
DATES: Fax written comments on the collection of information by January
3, 2011.
ADDRESSES: To ensure that comments on the information collection are
received, OMB recommends that written comments be faxed to the Office
of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer,
FAX: 202-395-7285, or e-mailed to oira_submission@omb.eop.gov. All
comments should be identified with the OMB control number 0910-new and
title ``Study of Clinical Efficacy Information in Professional Labeling
and Direct-to-Consumer (DTC) Print Advertisements for Prescription
Drugs.'' Also include the FDA docket number found in brackets in the
heading of this document.
FOR FURTHER INFORMATION CONTACT: Elizabeth Berbakos, Office of
Information Management, Food and Drug Administration, 1350 Piccard Dr.,
PI50-400B, Rockville, MD 20850, 301-796-3792,
Elizabeth.Berbakos@fda.hhs.gov.
SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has
submitted the following proposed collection of information to OMB for
review and clearance. Study of Clinical Efficacy Information in
Professional Labeling and Direct-to-Consumer (DTC)
Print Advertisements for Prescription Drug--(OMB Control Number
0910-New)
Section 1701(a)(4) of the Public Health Service Act (42 U.S.C.
300u(a)(4)) authorizes FDA to conduct research relating to health
information. Section 903(b)(2)(c) of the Federal Food, Drug, and
Cosmetic Act (FD&C Act) (21 U.S.C. 393(b)(2)(c)) authorizes FDA to
conduct research relating to drugs and other FDA-regulated products in
carrying out the provisions of the FD&C Act.
FDA regulations require that an advertisement that makes claims
about a prescription drug include a ``fair balance'' of information
about the benefits and risks of the advertised product, in terms of
both content and presentation (21 CFR 202.1(e)(5)(ii)). In past
research FDA has focused primarily on the risk component of the risk-
benefit ratio. In the interest of thoroughly exploring the issue of
fair balance, however, the presentation of effectiveness, or benefit,
information is equally important.
The FD&C Act requires that manufacturers, packers, and distributors
(sponsors) who advertise prescription human and animal drugs, including
biological products for humans, disclose in advertisements certain
information about the advertised product's uses and risks.\1\ By its
nature, the presentation of this risk information is likely to evoke
active trade-offs by consumers, i.e., comparisons with the perceived
risks of not taking treatment, and comparisons with the perceived
benefits of taking a treatment.\2\ Since FDA has an interest in
fostering safe and proper use of prescription drugs, an activity that
engages both risks and benefits, an in-depth understanding of
consumers' processing of this information is central to this regulatory
task.
---------------------------------------------------------------------------
\1\ For prescription drugs and biologics, the FD&C Act requires
advertisements to contain ``information in brief summary relating to
side effects, contraindications, and effectiveness'' (21 U.S.C.
352(n)).
\2\ See Schwartz, L., S. Woloshin, W. Black, et al., ``The Role
of Numeracy in Understanding the Benefit of Screening Mammography,''
Annals of Internal Medicine, 127(11), 966-72, 1997.
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Research and guidance to sponsors on how to present benefit and
efficacy information in prescription drug advertisements is limited.
For example, ``benefit claims,'' broadly defined, appearing in
advertisements are often presented in general language that does not
inform patients of the likelihood of efficacy and are often simply
variants of an ``intended use'' statement. In a content analysis of DTC
advertising,\3\ the researchers classified the ``promotional
techniques'' used in the advertisements. Emotional appeals were
observed in 67 percent of the ads while vague and qualitative benefit
terminology was found in 87 percent of the ads. Only 9 percent
contained data. For risk information, however, half the advertisements
used data to describe side-effects, typically with lists of side-
effects that generally occurred infrequently.
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\3\ Woloshin, S. and L. Schwartz, ``Direct to Consumer
Advertisements for Prescription Drugs: What Are Americans Being
Told,'' Lancet, 358, 1141-46, 2001.
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FDA regulations require that prescription drug advertisements that
make (promotional) claims about a product also include risk information
in a ``balanced'' manner (21 CFR 202.1(e)(5)(ii)), both in terms of the
content and presentation of the information. This balance applies to
both the front (aka ``display'') page of an advertisement, as well as
the brief summary page. However, beyond the ``balance'' requirement
limited guidance and research exists to direct or encourage sponsors to
present benefit claims that are informative, specific, and reflect
clinical effectiveness data.
The purpose of this project is to: (1) Understand how physicians
process clinical efficacy information and how
[[Page 75478]]
they interpret approved product label information,\4\ (2) determine
physician preferences for alternative presentations of clinical
efficacy information in DTC advertising, and (3) examine how different
presentations of clinical efficacy information in DTC advertising
affect consumers' perceptions of efficacy and safety. Specifically, we
are interested in how physicians and consumers make risk/benefit
assessments and particularly, how consumers make such judgments in
response to variations in the efficacy presentations in the ``display''
(first) page of a DTC print ad. A particular concern is whether certain
presentations cause consumers to form skewed perceptions or unfounded
risk/benefit tradeoffs. Therefore, we will investigate to what extent
consumers, when provided with efficacy information, form perceptions
that correspond with clinically-based physicians' assessments of the
benefits, risks, and benefit/risk tradeoffs of the same drugs. These
studies will inform FDA's thinking regarding how manufacturers may
provide useful and non-misleading efficacy information in DTC print
advertisements.
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\4\ As part of this effort, a qualitative mental models
procedure was completed that helped us determine how physicians
think about the efficacy of potential pharmaceutical options (OMB
control no. 0910-0649).
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Design Overview
This study will be conducted in two concurrent, independent parts.
The first part will involve 2,500 consumers in an experimental
examination of variations of the display page of print DTC ads for two
fictitious drugs, closely approximating existing drugs for overactive
bladder (OAB) and benign prostatic hyperplasia (BPH). In the second
part, 600 general practitioners will review and evaluate a fictitious
``approved'' label for the same conditions. This design will allow us
to compare consumers' perceptions of efficacy with a more objective
measure of the true efficacy of the drug as measured by physician
perceptions of clinical efficacy from labeling.
Consumer experiment. In this part of the study, women who have been
diagnosed with or are at risk for OAB (self-designated based on
relevant symptoms) will be recruited and will view one version of a DTC
ad for a drug to treat OAB. Men who have been diagnosed with or are at
risk for BPH (self-designated based on relevant symptoms) will be
recruited and will view one version of a DTC ad for a drug to treat
BPH. Although the two conditions are somewhat specific to gender (men
can suffer from OAB but it is much more prevalent in women), they share
many of the same symptoms and characteristics. These medical conditions
afford us the ability to maintain various realistic manipulations of
placebo level and type of claim, as explained below. The graphical
elements and construction of the two ads will be comparable yet still
realistic.
Consumers will be randomly assigned to see 1 of 12 DTC print ads
within their respective medical condition and will answer questions
about the effectiveness and safety of the fictitious drug advertised in
them. These twelve experimental conditions will be created by examining
three independent variables in the following manner: Type of claim (2
levels: Treatment, prevention), placebo rate (3 levels: High, low,
none), and framing (2 levels: Single, mixed). Please note that the
numbers describing efficacy seen in the following table are for
illustration only. Actual numbers used will be determined by
pretesting.
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[GRAPHIC] [TIFF OMITTED] TN03DE10.010
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We will investigate variations of numerical presentation in two
different types of claims: treatment and prevention. Treatment claims
usually involve symptoms that may be alleviated by taking a given
prescription drug. This type of claim is directly observable and
somewhat testable by patients. If bothersome symptoms do not go away, a
patient can return to the healthcare provider with this information and
pursue additional options for treatment. In general, drugs that treat
symptoms typically show substantial percentages of people who
experience relief.
Prevention claims are important but due to their long-term nature,
potentially harder to communicate. A drug that prevents a negative
future event may not alleviate any symptoms
[[Page 75480]]
at all. Patients may feel no benefit from the drug and must trust their
healthcare provider and the data, as much as they can process it, that
the drug is providing a positive benefit for them. The nature of these
claims is such that the event being prevented is relatively rare, and
thus the numbers used to describe them are often very small. For
example, a cholesterol drug that reduces the risk of heart attack from
3 out of 100 to 2 out of 100 may not seem objectively large, but has
enormous consequences for millions of people and the healthcare system
in general. We chose to test this type of claim to determine whether
consumers are sensitive to the magnitude of the benefit in these
clinically meaningful but objectively small and usually asymptomatic
outcomes. While we will examine the current issues in both treatment
and prevention claims, we do not intend to make comparisons between the
two.
The second variable of interest is communication of a placebo rate.
Three levels will be examined. In addition to testing a control
condition with no placebo information, we will utilize a high and low
placebo rate to better understand if and how consumers use placebo
information. We see three possibilities: (1) People use placebo numbers
correctly, such that the low placebo group demonstrates higher
perceived efficacy than the high placebo group; (2) people use the
placebo numbers as a peripheral cue to mean ``science'' so there are no
differences between high and low placebo groups on perceived efficacy
but both are higher than the no placebo group; and (3) people do not
find the numbers meaningful or cannot process them, so the high and low
groups do not differ from one another and they do not differ from the
no placebo group. In an attempt to make our claims as realistic as
possible, we will maintain fairly low rates of prevention in the
prevention conditions. For this reason, in addition to the 12 cells in
the table previously illustrated in this document, we will also have an
additional control cell in which the effectiveness rates are quite
high--higher than could reasonably be expected but high enough to be
objectively noticeable (e.g., risk of bladder cancer on Drug X, 4/100;
risk of bladder cancer on placebo, 15/100). This additional condition
will provide confidence that our research manipulations are operating
as we expect.
Finally, we will examine the addition of mixed framing to the
traditional use of a single positive frame in a DTC ad. Mixed framing
provides the number of people who benefited and the number of people
who did not benefit, whereas positive framing provides only the number
of people who benefited. Only a few studies have actually measured this
mixed approach \5\ although risk communication guides recommend the use
of mixed framing to create more accurate perceptions.\6\ Although a
completely balanced design would also include a negative framing
condition (which would provide only the number of people who did not
benefit), we feel it is unrealistic to create an ad that would suggest,
for example, that ``Drug X did not work for 70 percent of people in
clinical trials,'' so we have chosen not to include negative framing in
our investigation.
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\5\ For a literature review, see Moxey, A., D. O'Connell, P.
McGettigan, et al., ``Describing Treatment Effects to Patients: How
They Are Expressed Makes a Difference,'' Journal of General Internal
Medicine, 18, 948-959, 2003.
\6\ Fagerlin, A., P.A. Ubel, D.M. Smith, et al., ``Making
Numbers Matter: Present and Future Research in Risk Communication,''
American Journal of Health Behavior, 31, S47-S56, 2007; Schwartz,
L.M., S. Woloshin, H.G. Welch, ``Risk Communication in Clinical
Practice: Putting Cancer in Context,'' Monograph of the National
Cancer Institute, 25, 124-133, 1999.
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In this part of the project, we are most interested in consumers'
perceived efficacy and safety, which we can then compare with ratings
physicians will provide based on the prescribing information, described
in the next section. We will also ask consumers questions to measure
their accuracy with regard to claims, their recall of the information
in the ad, and demographic questions that may influence their
responses, such as knowledge about their medical condition and their
level of numeracy.
Physician Study. Six hundred general practitioners \7\ will
participate in an Internet survey lasting no longer than 20 minutes.
They will complete two tasks during this time. In the first task, they
will evaluate a prescription drug label (also known as the prescribing
information, written for healthcare practitioners) for one of the two
fictitious drugs described in the consumer study below. To provide a
match for the variations of information in the DTC ads the consumers
will observe, physicians will be randomly assigned to see prescribing
information that varies in terms of claim type, placebo rates in
clinical trials, and the medical condition the drug treats (OAB or
BPH).
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\7\ Including internists, general practitioners, and family
practitioners.
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As part of this task, we will obtain timing and sequence
information on which sections of the label physicians examine. This
will enable us to have a deeper understanding of physicians' processing
of the prescribing information. We are not aware of existing literature
on this topic. Additionally, physicians will answer questions about the
efficacy and safety of the drug and quantitative questions about the
benefit shown in the clinical studies (as described in the label).
These questions have been designed such that they can be reasonably
compared with the responses of consumers who will answer the same
questions after viewing a corresponding DTC ad.
In the second task, physicians will see four versions of a print
DTC ad for a fictitious product for high cholesterol and will rank the
ads in order of how representative of the clinical data as the
physicians know it the ads are and how useful they believe the ads
would be for their patients.\8\ The four versions will be selected to
mirror the versions of the OAB/BPH drug that consumers will see in the
consumer experiment (i.e., low placebo, frame).
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\8\ To reduce burden, the physician sample will be split in this
task, so that half of the physicians see the four ad versions with
treatment claims and the other half see the four ad versions with
prevention claims. Type of claim is described in greater detail in
the consumer experiment section.
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Thus, this research will provide us with a rich data set in order
to address several questions: (1) How physicians process clinical
efficacy information and how they use approved product label
information, (2) how physicians' interpretations of clinical efficacy
information relate to their preferences for alternative DTC ad
presentations, and (3) which variations of information in DTC ads bring
consumers closer to or farther away from the conclusions of the
physicians regarding the same drugs.
FDA estimates the burden of this collection of information as
follows:
The total respondent sample for this data collection is 3,400. We
estimate the response burden to be 20 minutes in the first part and 15
minutes in the second part, for a burden of 906 hours.
In the Federal Register of June 16, 2010 (75 FR 34142), FDA
published a 60-day notice requesting public comment on the proposed
collection of information. No comments were received on the paperwork
burden.
FDA estimates the burden of this collection of information as
follows:
[[Page 75481]]
Table 1--Total Estimated Annual Reporting Burden \1\
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Annual
21 CFR Section Number of frequency per Total annual Hours per Total hours
respondents response responses response
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Physician survey--pretest....... 100 1 100 .33 33
Physician survey--main study.... 600 1 600 .33 198
Consumer experiment--pretest.... 200 1 200 .25 50
Consumer experiment--main study. 2,500 1 2,500 .25 625
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Total....................... 906
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
Dated: November 30, 2010.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2010-30385 Filed 12-2-10; 8:45 am]
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