[Federal Register Volume 73, Number 229 (Wednesday, November 26, 2008)]
[Notices]
[Pages 72058-72062]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E8-28065]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

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


Agency Information Collection Activities; Proposed Collection; 
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.

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SUMMARY: The Food and Drug Administration (FDA) is announcing an 
opportunity for public comment on a 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 a study examining the impact 
on consumer comprehension of inclusion of a toll-free number to report 
side effects in direct-to-consumer (DTC) prescription drug television 
advertisements.

DATES: Submit written or electronic comments on the collection of 
information by January 26, 2009.

ADDRESSES: Submit electronic comments on the collection of information 
to http://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 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: 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.

Toll-Free Number for Consumer Reporting of Drug Product Side Effects in 
Direct-to-Consumer Television Advertisements for Prescription Drugs

    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 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

[[Page 72059]]

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 online at http://www.fda.gov/ohrms/dockets/
ac/oc08.html#RCAC.
Relevant Prior History and Research
    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 
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 the 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 online at http://www.fda.gov/OHRMS/DOCKETS/
98fr/E8-25670.pdf.

Proposed Research
    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 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. As cognitive load increases, 
more mental resources are necessary to process and understand the 
information.\1\ 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 in the following paragraphs before examining the 
details of the research design.
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    \1\ Chandler, P. and J. Sweller, ``Cognitive Load Theory and the 
Format of Instruction.'' Cognition and Instruction, 8(4), 293-332, 
1991.
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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 locating the toll-free statement here confuses consumers or 
provides no information for them

[[Page 72060]]

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 if it is located 
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. The usefulness of the 
toll-free statement, however, may improve in this condition relative to 
those discussed above 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 will be able to disregard it to 
focus on the risk information when desired. 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 in the long run.
2. Statement Wording
    The second variable, statement type, will have two executions of 
statement language: The language from FDAAA versus the language used in 
the TFNR 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/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 
``burnout'' 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 for a short amount of time may 
not give consumers enough time to read and process the message, 
resulting in lower comprehension of the message but no impact on the 
comprehension of the risk information. Alternatively, displaying the 
toll-free statement for a longer period of time may wipe away memory 
traces of the risks from the major statement, resulting in lower risk 
comprehension. Whether this longer duration increases the usefulness of 
the toll-free statement itself is an empirical question. 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, given the 
limited cognitive capacity of viewers. In examining this variable, we 
are exploring the parameters of this tradeoff.
Design Overview
    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: (1) Before the major statement of risks, (2) during 
the major statement of risks, (3) after the major statement of risks, 
or (4) 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
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                                            Statement Type
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          Placement                   FDAAA                 TFNR
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Before major statement of     ....................  ....................
 risks
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During major statement of     ....................  ....................
 risks
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[[Page 72061]]

 
After major statement of      ....................  ....................
 risks
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During the whole ad           ....................  ....................
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Plus:

 
 
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Control (no toll-free statement)
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    Part two of the study will examine four variations in the duration 
of the toll-free statement using the language from FDAAA: (1) Short 
(approximately 3 seconds after the major statement), (2) long 
(approximately 6 seconds after the major statement), (3) during the 
whole ad, and (4) 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.

                          Part Two: Duration\*\
                                  4 x 1
 
 
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Short (Approximately 3 seconds)
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Long (Approximately 6 seconds)
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During the whole ad
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Control (no toll-free statement)
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\*\Using FDAAA statement

    Part three of the study will examine two variations in the 
prominence of the toll-free statement using the language from FDAAA: 
Spoken with only the Web site and telephone number in superimposed 
text; or spoken with the full statement superimposed in text. Both 
variants in part three will place the toll-free statement after the 
major statement of risks. There will also be a control condition in 
which the statement does not appear at all.

                        Part Three: Prominence\*\
                                  3 x 1
Audio Only (spoken after major statement of risks, website and phone
 number on screen)
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Extra Prominent (spoken after major statement of risks, entire toll-free
 statement on screen)
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Control (no toll-free statement)
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\*\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 promotion 
for prescription treatment of high blood pressure, 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.
Procedure
    Participants will see an advertising pod of four ads: Two non-DTC 
ads (fillers), a DTC ad for a fictitious high blood pressure 
medication, and a 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 required to be implemented in DTC 
TV ads. That

[[Page 72062]]

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 participants 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 comprehension 
of the toll-free statement.
    Finally, demographic and health care utilization information will 
be collected. The entire procedure is expected to last approximately 15 
minutes. A total of 1,600 interviews will be completed. This will be a 
one-time (rather than annual) information collection.
Participants
    Data will be collected using an Internet protocol. Consumers over 
the age of 18 will be screened and recruited by the contractor to 
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 2 rounds of pretesting with 200 consumers 
in each round to refine the questionnaire and the stimuli before 
fielding the main study.
    FDA estimates the burden of this collection of information as 
follows:
    FDA estimates that 2,400 individuals will need to be screened to 
obtain a respondent sample of 400 for the pretests and 1,600 for the 
study. The screener is expected to take 30 seconds, for a total 
screener burden of 20 hours. The ad viewing and questionnaire are 
expected to take 15 minutes for the participants in the pretest and the 
main study, for a cumulative study burden of 500 hours. The estimated 
total burden for this data collection effort is 520 hours. The 
respondent burden is provided in table 1 of this document:

                                 Table 1--Estimated Annual Reporting Burden \1\
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                                            Annual Frequency     Total Annual      Hours per
            No. of Respondents                per Response        Responses        Response       Total Hours
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2,400 (screener)                                           1              2,400          .008                 20
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400 (pretest)                                              1                400           .25                100
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1,600 (study)                                              1              1,600           .25                400
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Total                                                                                                        520
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

    Please note that on January 15, 2008, the FDA Division of Dockets 
Management Web site transitioned to the Federal Dockets Management 
System (FDMS). FDMS is a Government-wide, electronic docket management 
system. Electronic comments or submissions will be accepted by FDA only 
through FDMS at http://www.regulations.gov.

    Dated: November 19, 2008.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E8-28065 Filed 11-25-08; 8:45 am]
BILLING CODE 4160-01-S