Document ID: FDA-2008-N-0595-0008
Agency: fda
Document Type: Notice
Title: Agency Information Collection Activities; Proposals, Submissions, and Approvals
Posted Date: 2009-08-18T04:00Z

[Federal Register: August 18, 2009 (Volume 74, Number 158)]
[Notices]
[Page 41703-41710]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr18au09-52]

[[Page 41703]]                                                                                                                                                                                          Hammer: Menck 1,7002RMS impulse2Peak

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2008-N-0595]

Agency Information Collection Activities; Submission for Office
of Management and Budget Review; Comment Request; Experimental Study:
Toll-Free Number for Consumer Reporting of Drug Product Side Effects in
Direct-to-Consumer Television 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
September 17, 2009.

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: 202-395-6974, or e-mailed to oira_submission@omb.eop.gov. All
comments should be identified with the OMB control number 0910--New and
the title ``Experimental Study: Toll-Free Number for Consumer Reporting
of Drug Product Side Effects in Direct-to-Consumer Television
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 (HFA-710), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857, 301-796-3792.

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.

Experimental Study: Toll-Free Number for Consumer Reporting of Drug
Product Side Effects in Direct-to-Consumer Television Advertisements
for Prescription Drugs--(OMB Control Number 0910--New)

    The Federal Food, Drug, and Cosmetic Act (the 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. For prescription drugs and
biologics, the act requires advertisements to contain ``information in
brief summary relating to side effects, contraindications, and
effectiveness'' (21 U.S.C. 352(n)). FDA is responsible for enforcing
the act and implementing regulations.
    On September 27, 2007, the President signed into law the Food and
Drug Administration Amendments Act (FDAAA) (Public Law 110-85). Title
IX of FDAAA amends section 502(n) of the act (21 U.S.C. 352) by
requiring printed direct-to-consumer (DTC) advertisements for
prescription drug products to include the following statement printed
in conspicuous text: ``You are encouraged to report negative side
effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch,
or call 1-800-FDA-1088.'' Title IX of FDAAA also requires the Secretary
of Health and Human Services (the Secretary), in consultation with the
Risk Communication Advisory Committee (RCAC), to conduct a study not
later than 6 months after the date of enactment of FDAAA to determine
if this statement is appropriate for inclusion in DTC television
advertisements for prescription drug products. As part of this study,
the Secretary shall consider whether the information in the statement
described previously in this paragraph would detract from the
presentation of risk information in a DTC television advertisement. If
the Secretary determines that the inclusion of such a statement would
be appropriate for television advertisements, FDAAA mandates the
issuance of regulations implementing this requirement, and for the
regulations to reflect a reasonable length of time for displaying the
statement in television advertisements. Finally, FDAAA requires the
Secretary to report the study's findings and any subsequent plans to
issue regulations to Congress.
    In accordance with the requirements of FDAAA, FDA convened a
meeting of the RCAC on May 15 and 16, 2008. A draft design for studying
this issue was proposed at that time and discussed by the advisory
committee. Based on comments received at that meeting, changes were
made to the proposed study design. The transcripts and materials from
that meeting can be found at http://www.fda.gov/ohrms/dockets/ac/
oc08.html#RCAC.

I. Background

    Section 17 of the Best Pharmaceuticals for Children Act (the BPCA)
(Public Law 107-109, January 4, 2002) required FDA to issue a final
rule mandating the addition of a statement to the labeling of each drug
product for which an application is approved under section 505 of the
act (21 U.S.C. 355). Under the BPCA, the statements must include: (1) A
toll-free number maintained by FDA for the purpose of receiving reports
of adverse events regarding drugs, and (2) a statement that the number
is to be used only for reporting purposes, and it should not be used to
seek or obtain medical advice (the side effects statement).
    On April 22, 2004, FDA published a proposed rule with a proposed
side effects statement for certain prescription drug product labeling
and a proposed side effects statement for certain over-the-counter drug
product labeling (69 FR 21778). In the proposed rule, FDA solicited
comments on a proposed statement that FDA believed comported with the
previously mentioned mandate in the BPCA. The agency received 12
comments suggesting changes to the specific wording proposed. The
agency also received several comments suggesting that FDA engage in
research to study the wording of the proposed side effects statement
with consumers. Among the reasons cited for testing the statement were
to: (1) Determine the best and most precise wording for the statement,
(2) evaluate consumer comprehension of the proposed statement, and (3)
address concerns that consumers who read the statement will mistakenly
call FDA in search of medical advice rather than seeking appropriate
medical treatment. In addition, during the clearance process for the
proposed rule, both the Office of Information and Regulatory Affairs of
OMB and the Office of the Assistant Secretary for Planning and
Evaluation of the Department of Health and Human Services suggested
that FDA conduct focus groups or other consumer studies to inform the
wording of the side effects statement.
    During the spring of 2006, to assist in developing this study, FDA
conducted two focus groups to gauge consumer understanding and
preferences for a number of proposed side effects statements and to
narrow the number of statements to be tested in subsequent experimental
research. In addition to the information collected on which versions of
the statements participants preferred, discussions showed that people
varied in their understanding of when to call FDA or their health care

[[Page 41704]]

practitioners and that some people would not call FDA even if they
experienced a serious side effect. Several people in the focus groups
suggested the addition of a Web site to report adverse side effects.
Based on the findings from the focus groups, nine statements were
selected for quantitative testing. A labeling comprehension experiment
was conducted with 1,674 men and women ranging in age from 21 to 95
with varying levels of education (OMB Control No. 0910-0497). The
results from that quantitative test found that only one of the versions
tested was rated as significantly less clear than the others, which
were all rated as generally clear and understandable. The results also
showed that participants reported they would not call FDA seeking
medical advice. Further, among those participants who said they would
call FDA, the majority indicated they would call their doctor for
medical advice, rather than FDA, regardless of the severity of the side
effect. Finally, participants indicated they could distinguish between
serious and non-serious side effects, reporting that they would seek
emergency medical care in the case of serious side effects. The report
of the study is available in the docket for the final rule (Docket No.
FDA-2003-N-0313). The final rule, Toll-Free Number for Reporting
Adverse Events on Labeling for Human Drug Products (TFNR) (73 FR 63886,
October 28, 2008), is available at http://www.fda.gov/OHRMS/DOCKETS/
98fr/E8-25670.pdf.
    In the Federal Register of November 26, 2008 (73 FR 72058), FDA
published a 60-day notice requesting public comment on the information
collection provisions. FDA received six comments in response to our
initial Federal Register notice, published on November 26, 2008. One of
these comments, from an anonymous citizen, did not require specific
responses, as it was outside the scope of the project (e.g., FDA
approves too many drugs; harmful drugs are ``being foisted on the
population''), although it could be viewed as a statement of support
for conducting the research.

II. Comments on the Information Collection

    In the following section, we outline the issues raised in the
comments and provide our responses.
    (Comment 1) Do not place the toll-free statement in television ads
because it is better placed within written materials that accompany
prescription drugs. Some system for enforcing the legitimacy of calls
is necessary, otherwise callers with an ``agenda'' or ``the
uninformed'' could ``doom medicines for no reason.''
    (Response) This comment mostly applies to MedWatch procedures that
are outside the scope of the proposed research. This study is
addressing the understanding of information in the ad. We have notified
the appropriate parties in the agency of this comment.
    (Comment 2) The comment supports DTC advertising that is
educational and ``delayed until postmarketing surveillance data are
collected and assessed.'' DTC television ads should include a toll-free
statement. Overall, this comment supports the proposed research, but
includes the following specific suggestions: (1) The toll-free
statement is best placed after the risk information and (2) it should
be placed during the presentation of non-life-threatening or minor side
effects.
    (Response) We agree that placement during non-life-threatening or
minor side effects may be the best placement for the toll-free
statement. In a television ad, however, that information is presented
in a very short amount of time, sometimes only seconds (and this varies
depending on the drug product). We have designed our study to allow the
data to show for us the best placement of the statement.
    (Comment 3) Neither of the proposed toll-free statements addresses
whether consumers can distinguish between serious and non-serious side
effects. A simulation study should be used to assess this issue.
    (Response) We refer this comment to previous research conducted by
FDA on this topic, described previously. This study found that
participants were easily able to distinguish between serious and non-
serious side effects and that they reported an ability to take the
right action with regard to each one.
    (Comment 4) FDA should post the proposed questionnaire, the primary
endpoint(s) of the study with action standards, and provide the mock
advertisement to interested parties for use in their research.
    (Response) The proposed questionnaire has been and continues to be
available upon request. We agree that threshold levels and primary
endpoints were not well explained in the 60-day notice and have worked
to correct that in the 30-day notice. Please note the addition of
specific hypotheses and the analysis plan. At the conclusion of our
data collection, we will make the advertisement available to those who
request it.
    (Comment 5) Adequate provision issues may not be considered or
addressed. Multiple telephone numbers or Web sites may confuse
consumers. Use alternate wording for the toll-free statement: ``For
information about PRODUCT X or to report side effects, see our ad in --
---- magazine.'' Include payment assistance information, as this is
often currently included in television ads.
    (Response) We have designed the stimuli ad to closely approximate
an actual DTC ad, including adequate provision measures and other
supers. Division of Drug Marketing, Advertising, and Communications
reviewers have examined the script and storyboard to ensure that the ad
meets regulatory requirements. The contractor producing the ad has
extensive experience with this type of production and provided
additional quality control measures. In directing us to complete this
research, Congress was likely concerned about the same issues expressed
by this comment, i.e., that the toll-free statement may be confusing.
That is one of the main research questions we will address. In terms of
wording, Congress directed us to test specific language. In addition to
this language, we propose to test another version that was found most
acceptable in previous usability research conducted by the agency.
Finally, because payment assistance information is relatively new, not
universal, and not required by regulation, we have not included this
statement in our stimuli ads.
    FDA has contracted with a professional multimedia company to create
ad stimuli. In addition, FDA has instituted a procedure of extensive
pretesting of the ad stimuli to be used. Our extensive experience with
current and past DTC ads, pretesting, and collaboration with the
contractor should ensure realistic ads that will enable us to
successfully investigate our experimental variables.
    (Comment 6) Study multiple medical conditions, including
symptomatic and asymptomatic conditions; diseases that affect different
age groups; sufferers and non-sufferers; and consumers with varying
degrees of knowledge about their medical conditions.
    (Response) We do not have the resources to create mock ads to test
multiple medical conditions. We have no reason to suspect that the
principles we study in this medical condition (e.g., placement,
duration, wording, prominence) would be different when applied to an ad
for another medical condition. We welcome other parties to extend the
current research by applying it to other conditions. We will ask
respondents about their knowledge of their medical conditions and will

[[Page 41705]]

conduct analyses to see if this variable plays a role in their
responses.
    We have decided, however, to recruit for the study two distinct
populations: Those who have been diagnosed with high blood pressure and
a general population sample. This approach will allow us to determine
whether diagnosed individuals and other people who may be exposed to
such television advertising will differ in their responses to the ad.
    (Comment 7) Using the condition where the toll-free statement is
present during the whole ad to control for novelty will increase rather
than decrease the attention to the statement.
    (Response) We agree that the condition in which the toll-free
statement appears during the entire ad may increase notice of it. We
think there is also a good possibility that it might be ignored, in
such a way that the statement might be more prominent in other
conditions. To control for novelty, participants will see an unrelated
DTC ad with the toll-free statement presented the same way as the test
ad before they see the test ad. This may control for novelty in the
test ad and may attenuate the belief that our test product has some
unique quality that causes it to need a special toll-free statement.
    (Comment 8) This protocol will take much longer than 15 minutes.
    (Response) Because we are also concerned that this protocol will
take longer than 15 minutes, we have revised our burden estimate to
reflect a 20-minute protocol. Also, to ensure that all test parameters
are met, including timing of experiment, we have budgeted for 2
pretests of 700 individuals each.
    (Comment 9) The placement and duration variables should be removed
from study because regardless of placement, the statement may interrupt
the flow of the most important information.
    (Response) These are empirical questions. We will not know the
answer to either of these questions until we collect data.
    (Comment 10) Remove the audio-only condition because this
eliminates the hearing-impaired population. Include visually and
hearing-impaired persons to more accurately represent the population.
    (Response) Even in our audio-only condition as originally proposed,
the Web site and phone numbers were placed on screen. Current
requirements for the most important risk information (i.e., the major
statement) are that it be placed in the audio portion of the ad. Thus,
this is a reasonable condition to test. Upon further discussion,
however, we agree that we do not need two distinct extra-prominent
conditions, and will test only one. We do not plan to actively exclude
people with audio or visual impairments from the study but we do not
have the resources to actively recruit them.
    (Comment 11) High blood pressure may not be the most representative
condition for a general sample of consumers ``over the age of 18.'' The
tested sample population should be representative of actual sufferers
of the condition being advertised.
    (Response) We agree that this is an important consideration. Upon
further discussion, we have decided to recruit for the study two
distinct populations: Those who have been diagnosed with high blood
pressure and a general population sample. This approach will allow us
to determine whether diagnosed individuals and other people who may be
exposed to such television advertising will differ in their responses
to the ad.
    (Comment 12) Remove the fourth commercial for an unrelated medical
condition because it does not contribute to the study and may confound
results.
    (Response) Study participants will see four ads--the second ad will
be an unrelated DTC ad and the fourth ad will be the test ad. We
propose to include the other DTC ad with the matching toll-free
statement parameters so that consumers do not think that our test ad
reflects a special product that needs a special warning. It also may
attenuate the effect of novelty.
    (Comment 13) Because the toll-free statement may artificially
increase impact of risk information, FDA should test information
gleaned from the presence of the toll-free statement in print ads
first.
    (Response) FDA has not collected any information on the presence of
the statement in print ads, although we agree this would be valuable
information. Moreover, Congress has instructed us specifically to test
the toll-free statement in television ads.
    (Comment 14) Including the manufacturer's toll-free number instead
of the FDA contact number may help to mitigate the possibility that the
toll-free statement artificially increases the impact of risk
information.
    (Response) Sponsors already include the manufacturer's telephone
number in all ads as a way to fulfill one part of the adequate
provision requirement. The current study does not examine the
replacement of that number with the toll-free statement, but instead
the statement's inclusion above and beyond current requirements.
    (Comment 15) The agency's expectation of yielding a sample of 2,000
people from a total of 2,400 is unrealistic based on a typical response
rate of 5 percent.
    (Response) We do not expect to yield a sample of 2,000 people from
a total of 2,400. As shown in Table 1 of this document, we have revised
our sample numbers.
    (Comment 16) How well can an Internet study simulate a television
environment?
    (Response) We agree that simulating an everyday television-watching
environment would increase the realism of the study. Participation in
an experiment in any context, however, is unlikely to perfectly do so.
We do not believe that a mall-intercept administration would increase
the realism of the study and a phone-based survey is not feasible,
given the modality of the advertisement in question. Moreover, an
Internet study may be as close to the television-watching environment
as any other method because participants will be in their own homes and
some participants already watch streaming video on their computers.
    (Comment 17) What are the thresholds for interference
(``detraction'') in this study? Specifically, will the statement be
included only if it does not affect risk comprehension at all, or if it
does not affect risk comprehension ``much''--and if this is the case,
what is too much?
    (Response) If the study demonstrates that the inclusion of the
toll-free statement does not interfere with the processing of the risk
information, then Congress is likely to mandate its inclusion. If the
data demonstrate some detraction from risk information, then the
decision becomes more complicated. As the interference between the
toll-free statement and the risk information increases, the less likely
it is that it will be mandated. A tradeoff analysis will have to be
conducted and this study will be only one part of the determination.
That is, the amount of detraction will have to be weighed against the
benefit of including the statement and this benefit will be determined
in part by public health concerns and analysis of MedWatch data.
    (Comment 18) Participants will see the test ad three times and this
may cause problems.
    (Response) Participants will see the test ad only once after seeing
three other filler ads, one of which will be an unrelated DTC ad.
    (Comment 19) The current proposed study is comprehensive and
appropriate to address the primary research questions under
consideration.

[[Page 41706]]

    (Response) Thank you.
    (Comment 20) The toll-free statement in the unrelated DTC ad should
be presented in the same way as in the test ad.
    (Response) We had planned to do so.
    (Comment 21) The questionnaire does not specifically address the
risk of nontreatment of the disease condition.
    (Response) FDA acknowledges that this study does not address this
risk. Nevertheless, this is outside the scope of the current
investigation.
    (Comment 22) Ask if respondents suffer from diabetes, high
cholesterol, obesity, or the condition treated in the unrelated DTC ad.
    (Response) We plan to ask about the state of respondent's health.
In considering this comment, we have added additional questions to the
questionnaire. Please see the revised questionnaire for details.
    (Comment 23) Question 7 in the questionnaire is vague and should be
placed earlier in the questionnaire.
    (Response) Question 7, which originally asked participants in an
open-ended fashion to report on ``some information written on the
screen'' has been changed. We now ask participants which of several
options they saw and follow that up with an open-ended question about
what the statement means to them. We do not wish to move this question
series earlier in the questionnaire because it is not one of our main
dependent measures.
    (Comment 24) It is unclear how FDA plans to analyze results from
this research, particularly what action consumers are expected to take
after they have heard and understood the toll-free statement.
    (Response) The purpose of this research is not to determine what
action consumers will take after seeing the ad. We addressed these
issues in the labeling comprehension study described at the beginning
of this notice (Docket No. FDA-2003-N-0313). The purpose of the current
proposed study is to determine whether the risk information is
adequately comprehended and whether the toll-free statement is
noticeable and recalled.

III. Revised Study

Experimental Study: Toll-Free Number for Consumer Reporting of Drug
Product Side Effects in Direct-to-Consumer Television Advertisements
for Prescription Drugs--(OMB Control Number 0910--New)

    Based in part on these comments, further research discussions, and
the input of the RCAC on May 16, 2008, we propose the following revised
design, hypotheses, and analysis plan.

A. Overview

    This study will examine the placement of the toll-free statement
and the length of time the statement is presented on screen in a DTC
television advertisement for a prescription drug. The primary dependent
measure of interest is consumer comprehension of the important risk
information in the advertisement. This study will also examine
potential differences in comprehension based on the wording of the
toll-free statement and the prominence of the statement.
    The application of a new piece of information for viewers of DTC
ads presents logistical challenges. From a research perspective, the
primary issue under investigation is how to impart additional
information without increasing ``cognitive load,'' thus leading to
information overload. Cognitive load is an index of the memory demands
necessary to process a set of information (Ref. 1). As cognitive load
increases, more mental resources are necessary to process and
understand the information. DTC ads are already quite dense when
compared to ads for other products. The risk information in the major
statement of the ad should not be compromised by the addition of the
toll-free statement. At the same time, it is preferable that the risk
information and the toll-free statement information are presented in
such a way that both are understandable. We have chosen a set of
variables in the current study to investigate issues of cognitive load.
They are described briefly below before examining the details of the
research design.
1. Placement
    The location of the toll-free statement may facilitate or detract
from the risk information in the major statement. We have chosen three
locations for this information to test which location results in the
greatest communication of the risks of the drug and the concept that
side effects can be reported. It is possible that locating the toll-
free statement before the major statement provides a ``prime'' for the
risk information that follows; that is, the mention of side effects in
the toll-free statement will cause consumers to start thinking about
side effect-related information, which facilitates comprehension of the
risk information that follows. In this case, the two conceptual pieces
of information may flow together easily. Conversely, it is possible
that the toll-free statement confuses consumers or provides no
information for them because they have not yet heard any risk
information. Thus, without context, the statement lacks applicability.
    Placing the toll-free statement during the major statement likely
reduces the comprehension of the risk information for the drug because
it divides viewer's attention between two competing pieces of
information. It is possible, however, that the juxtaposition of these
two informational concepts are complimentary and therefore do not
conflict.
    The toll-free statement may serve the best role after the risk
information has been presented. In this case, participants have been
told about the risks and side effects of the drug before they are told
they may report this information. This essentially primes the toll-free
statement with the major statement. We do not expect this placement to
interfere with the comprehension of risk information, as it is not
present during the voicing of risks and has not been introduced to
viewers at this point. In addition, the usefulness of the toll-free
statement may improve in this condition relative to those discussed in
the previous paragraphs because viewers have been provided with
context.
    Over time, it is likely that the toll-free statement will become
part of the background of the ads as people become accustomed to seeing
this statement in all DTC ads. In this respect, people will have the
statement as an option if needed but may be able to disregard it to
focus on the risk information otherwise. Thus, we are testing a
condition in which the toll-free statement will be present during the
entire ad. This test condition will control for the effect of novelty
arising from the fact that consumers have not previously seen this type
of statement in TV ads. Presence of the statement during the entire ad
may increase noticeability of the toll-free statement initially, but
will be unlikely to interfere with risk information over time.
2. Statement Type
    The second variable, statement type, will have two executions of
statement language: The language from the FDAAA versus the language
used in the final rule, Toll-Free Number for Reporting Adverse Events
on Labeling for Human Drug Products Rule (TFNR; Public Law 107-109,
January 4, 2002), and previously tested by FDA. The wording from these
two statements is as follows:
     ``You are encouraged to report negative side effects of
prescription drugs to the FDA. Visit www.fda.gov/

[[Page 41707]]

medwatch, or call 1-800-FDA-1088.'' (FDAAA)
     ``Call your doctor for medical advice about side effects.
You may report side effects to FDA at 1-800-FDA-1088 or www.fda.gov/
medwatch.'' (TFNR)
    We think it is important to test both the toll-free statement
version in FDAAA and the version that we have previously tested with
actual consumers. The most obvious reason for this is to make sure that
the statement is maximally readable and understandable. It may be
valuable, however, to test two statements for another reason.
    If the toll-free statement is enacted in broadcast ads, it is
possible that because of the boilerplate language, some amount of
habituation will occur. That is, after viewers have seen the same
language in multiple ads for multiple products, they may ``tune out''
and not pay attention to the toll-free statement at all. If we test two
versions of the statement and find both acceptable, it would be
possible to either allow sponsors to choose one statement versus
another or to suggest some alternating of the two statements. This is a
long-term idea, however, and finding appropriate wording is the primary
goal of investigating this variable.
3. Duration
    Congress specifically mandates that we investigate the duration of
the display of the toll-free statement. As with placement, the length
of time the toll-free statement is presented on screen may influence
the cognitive load in the ad. For experimental control, we will look at
the duration of the statement while holding placement in the ad (after
the major statement of risks) constant. Although this placement should
not interfere with the processing of the risk information, it is
possible that the duration influences the take-away message from the
ad. For example, having the statement on screen for a short amount of
time may not give consumers enough time to read and process the toll-
free message. This may result in lower comprehension of the message but
may have no impact on the comprehension of the risk information.
Alternatively, displaying the toll-free statement for a longer period
of time may remove memory traces of the risks from the major statement,
resulting in lower risk comprehension. To determine whether this longer
duration increases the usefulness of the toll-free statement itself, we
will compare these short and long durations to instances where the
toll-free statement is present during the entire ad and where there is
no toll-free statement at all.
4. Prominence
    In addition to superimposing the toll-free statement on the screen
during the ad, there are other methods available to increase the
prominence of the statement. In particular, having the statement read
aloud in the ad voiceover while the statement is on the screen may be
considered particularly prominent. Does the additional prominence of
the statement compromise the comprehension of the risk information in
the major statement? If not, does the additional prominence result in a
greater understanding of the toll-free statement itself? It is likely
that there is a tradeoff between the gains of emphasizing the toll-free
statement and the comprehension of the risk information. In examining
this variable, we are exploring the parameters of this tradeoff.

B. Design

    The design will consist of three parts. Part one will be a between-
subjects factorial design examining the placement of the toll-free
statement by the type of statement. The first variable, placement, will
have four levels: Before the major statement of risks, during the major
statement of risks, after the major statement of risks, or continuously
throughout the whole ad.
    In each condition the toll-free statement will appear in the ad as
superimposed text at the bottom of the screen. We will also include a
control condition in which the statement does not appear.

                  Part One: Placement by Statement Type
                                4 x 2 + 1
------------------------------------------------------------------------
                                            Statement Type
------------------------------------------------------------------------
          Placement                   FDAAA                 TFNR
------------------------------------------------------------------------
Before major statement of     ....................  ....................
 risks
------------------------------------------------------------------------
During major statement of     ....................  ....................
 risks
------------------------------------------------------------------------
After major statement of      ....................  ....................
 risks
------------------------------------------------------------------------
During the whole ad           ....................  ....................
------------------------------------------------------------------------

Plus:

-----------------------------------------------------------------------------------------------------------------
Control (no toll-free statement)
----------------------------------------------------------------------------------------------------------------

    Part two of the study will examine four variations in the duration
of the toll-free statement using the language from FDAAA: Short (on
screen for approximately 3 seconds after the major statement), long (on
screen for approximately 6 seconds after the major statement), on
screen during the whole ad, and the control condition of no toll-free
statement included. These times were adopted by calculating how long it
would take a person reading at an average reading speed to read the
statement. As in the first part of this study series, the toll-free
statement will appear as superimposed text and a control condition in
which the toll-free statement does not appear will be included.

[[Page 41708]]

                          Part Two: Duration\*\
                                  4 x 1

-------------------------------------------------------------------------
Short (on screeen for approximately
3 seconds after major statement)
------------------------------------------------------------------------
Long (on screen for approximately
6 seconds after major statement)
------------------------------------------------------------------------
During the whole ad
------------------------------------------------------------------------
Control (no toll-free statement)
------------------------------------------------------------------------
\*\Using FDAAA statement

    Part three of the study will examine two variations in the
prominence of the toll-free statement using the language from the
FDAAA: Spoken after the major statement with only the Web site and
phone number in superimposed text, and a control condition where the
toll-free statement is presented visually after the major statement.

                        Part Three: Prominence\*\
                                  2 x 1
Extra Prominent (spoken after major statement of risks, Web site and
 phone number on screen)
------------------------------------------------------------------------
Control (after major statement of risks)
------------------------------------------------------------------------
\*\Using FDAAA statement

    We will investigate these issues in one disease condition, high
blood pressure, because high blood pressure has a high incidence rate
in the population, is a public health concern, and is likely to occur
in both males and females. Further, because there is little broadcast
promotion for prescription treatment of high blood pressure at this
time, participants should be less familiar with DTC television ads for
this type of drug, reducing the potential influence of prior
experience.
    Our primary dependent variable is comprehension of the risk
information mentioned in the major statement. In addition to this
variable, we will also examine comprehension of benefit information. We
will also examine the noticeability and comprehension of the toll-free
statement.

C. Procedure

    Participants will see a cluster of four ads: Two 15-second non-DTC
ads (fillers), an approximately 60-second DTC ad for a fictitious high
blood pressure medication, and a 30-second DTC ad for an unrelated
medical condition with the same toll-free statement included. We
include two DTC ads with the toll-free statement in our protocol
because this better approximates what will happen if this statement is
enacted. That is, viewers will see the statement in all DTC ads for all
products. In this study, we want to avoid the suggestion that there is
something particular about the high blood pressure drug class that
causes the statement to be mandated. Thus, we will show multiple DTC
ads but ask questions regarding only the ad which has been manipulated
to test our hypotheses. To maximize response information, the test ad
will always be the last ad they see.
    After viewing the ads, a structured interview will be conducted.
Participants will answer questions about the high blood pressure DTC
test ad they have seen. Questions will examine a number of important
perceptions about the advertised product, including risk comprehension,
risk recall, benefit comprehension, benefit recall, behavioral
intention, noticeability of the toll-free statement, and recall of the
toll-free statement.
    Finally, demographic and health care utilization information will
be collected. The entire procedure is expected to last approximately 20
minutes. A total of 6,000 interviews will be completed. This will be a
one-time (rather than annual) information collection.

D. Participants

    Data will be collected using an Internet protocol. Two samples of
consumers will be recruited: One sample of individuals diagnosed with
high blood pressure and another sample of consumers over the age of 21.
Both groups will represent a range of education levels. Because the
task presumes basic reading abilities, all selected participants must
speak English as their primary language.
    FDA proposes to conduct two rounds of pretesting with 700 consumers
in each round to refine the questionnaire and the stimuli before
collecting data for the main study.

Hypotheses

    Overall, we expect effects to be stronger in the high blood
pressure sample than in the general population sample, as high blood
pressure sufferers will likely have higher involvement with the medical
condition.
1. Risk Comprehension
    This section explains the following:
     Any inclusion of the toll-free statement will reduce the
comprehension of risk information.
    (Risk comprehension will be highest in control condition for all
analyses)
     Placement:
    Conditions in which the statement is presented after the major
statement and the statement is present for the whole ad will reduce
comprehension least.
    (After control condition, risk comprehension will be highest in
conditions where statement is present for whole ad or after the major
statement; risk comprehension will be lowest when statement is
presented during or before the major statement).

[[Page 41709]]

     Wording: Type of statement will not influence risk
comprehension.
     Placement x Wording: This analysis is exploratory
     Duration:
    Statement will interfere with risk comprehension less when
presented in the whole ad than when presented for briefer periods.
    Short duration will result in lower risk comprehension than long
duration because it will be displayed for a short time, causing
attention to shift twice in quick succession
    (Risk comprehension highest in control condition, followed by whole
ad condition followed by long duration, and, finally, short duration)
     Prominence: Prominence of statement will not affect risk
comprehension.
2. Benefit Comprehension
    This section explains the following:
     Any inclusion of the toll-free statement will reduce the
comprehension of benefit information.
    (Benefit comprehension will be highest in control condition for all
analyses)
     Placement:
    Conditions in which the statement is presented after the major
statement and the statement is present for the whole ad will reduce
comprehension least.
    (After control condition, benefit comprehension will be highest in
conditions where statement is present for whole ad or after the major
statement; benefit comprehension will be lowest when statement is
presented during or before the major statement).
     Wording: Type of statement will not influence benefit
comprehension.
     Placement x Wording: This analysis is exploratory
     Duration:
    Statement will interfere with benefit comprehension most when
presented in the whole ad than when presented for briefer periods after
the major statement.
    No prediction of differences between short and long duration of
statement on benefit comprehension.
    (Benefit comprehension highest in control condition, followed short
and long duration conditions together, followed by condition where
statement is present in whole ad)
     Prominence: Prominence of statement will not affect
benefit comprehension.
3.Toll-Free Statement Recall
    This section explains the following:
     Toll-free statement recall will be higher in any condition
where it is included in the ad.
     Placement:
    Recall of statement will be highest in conditions where it is on
screen for the whole ad and where it is placed after the major
statement.
     Wording: This analysis is exploratory.
     Placement x Wording: This analysis is exploratory
     Duration:
    Recall of the statement will be greatest in the condition where it
is present for the whole ad, followed by the condition in which it is
located after the major statement.
     Prominence:
    Recall of the statement will be higher in the Extra Prominent
condition than in the condition in which it is only in super form after
the major statement.
4. Behavioral Intention
    This section explains the following:
     This analysis is exploratory and for completeness.

Analysis Plan

    We will conduct the following analyses separately for the general
population sample and the high blood pressure sufferers sample. Once
these separate analyses are completed, we will conduct the analyses
with the samples combined, using the type of sample as a moderator
variable to determine whether any effects differed significantly
between the groups.
    Part 1: We will test whether there is a main effect of placement on
our main dependent variables (i.e., risk comprehension, benefit
comprehension, and behavioral intention) using one-way Analysis of
Variants (ANOVAs) (four placement conditions, plus control condition).
We will conduct ANOVAs that assess the main effect of placement (four
placement conditions), the main effect of statement type, and the
interaction between placement and statement type on our main dependent
variables. We will examine logistic regression models predicting toll-
free statement recall from placement (four placement conditions, plus
control condition), and from placement, statement type, and the
interaction between placement and statement type. We will conduct these
analyses both with and without covariates (e.g., demographic and health
characteristics) included in the model. In addition, we will test
whether any main effects are moderated by other measured variables
(e.g., time spent viewing the ad, demographic and health
characteristics). If any main effects are significant, we will conduct
pairwise-comparisons to determine which conditions are significantly
different from one another. We will also conduct planned comparisons in
line with our hypotheses (see Hypotheses in this document).
    Part 2: We will test whether there is a main effect of duration on
our main dependent variables using one-way ANOVAs and logistic
regression models. We will examine these analyses both with and without
covariates (e.g., demographic and health characteristics) included in
the model. In addition, we will test whether the main effect is
moderated by other measured variables (e.g., time spent viewing the ad,
demographic and health characteristics). If the main effect is
significant, we will conduct pairwise-comparisons to determine which
conditions are significantly different from one another. We will also
conduct planned comparisons in line with our hypotheses (see Hypotheses
in this document).
    Part 3: We will test whether there is a main effect of prominence
on our main dependent variables using one-way ANOVAs and logistic
regression models. We will examine these analyses both with and without
covariates (e.g., demographic and health characteristics) included in
the model. In addition, we will test whether the main effect is
moderated by other measured variables (e.g., time spent viewing the ad,
demographic and health characteristics).
5. Pretesting of Stimuli
    The key to our study is the reasonableness and appropriateness of
the stimuli we use to approximate television DTC prescription drug ads.
Because the particular images are subjective, we will conduct extensive
pretesting with consumers similar to our main target audience. This
pretesting will involve 700 individuals in 2 waves. The purpose of the
pretesting is to ensure that the stimuli are perceived as realistic.
During the pretesting stage, the primary dependent variable will be the
success of the particular manipulation. The pretesting will allow us to
make changes in the ad stimuli before the actual study commences, thus
making participants' time more valuable.

[[Page 41710]]

                                                     Table 1.--Estimated Annual Reporting Burden\1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                     Annual Frequency                            Hours per
                      21 CFR Section                          No. of Respondents       per Response    Total Annual  Responses    Response   Total Hours
--------------------------------------------------------------------------------------------------------------------------------------------------------
Screener, pretesting                                                         2,800                  1                    2,800          .03           84
--------------------------------------------------------------------------------------------------------------------------------------------------------
Questionnaire, pretesting                                                    1,400                  1                    1,400          .25          350
--------------------------------------------------------------------------------------------------------------------------------------------------------
Screener, study                                                             12,000                  1                   12,000          .03          360
--------------------------------------------------------------------------------------------------------------------------------------------------------
Questionnaire, study                                                         6,000                  1                    6,000          .33        1,980
--------------------------------------------------------------------------------------------------------------------------------------------------------
Total                                                      .......................  .................  .......................  ...........        2,774
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

IV. References

    1. Chandler, P. and J. Sweller, ``Cognitive Load Theory and the
Format of Instruction,'' Cognition and Instruction, 8(4), 293-332,
1991.

    Dated: August 11, 2009.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E9-19782 Filed 8-17-09; 8:45 am]

BILLING CODE 4160-01-S