[Federal Register Volume 86, Number 41 (Thursday, March 4, 2021)]
[Notices]
[Pages 12692-12696]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-04472]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2020-N-1228]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Study of Multiple 
Indications in Direct-to-Consumer Television Advertisements

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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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: Submit written comments (including recommendations) on the 
collection of information by April 5, 2021.

ADDRESSES: To ensure that comments on the information collection are 
received, OMB recommends that written comments be submitted to https://www.reginfo.gov/public/do/PRAMain. Find this particular information 
collection by selecting ``Currently under Review--Open for Public 
Comments'' or by using the search function. The title of this 
information collection is ``Study of Multiple Indications in Direct-to-
Consumer Television Advertisements.'' Also include the FDA docket 
number found in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: Ila S. Mizrachi, Office of Operations, 
Food and Drug Administration, Three White Flint North, 10A-12M, 11601 
Landsdown St., North Bethesda, MD 20852, 301-796-7726, 
PRAStaff@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 Multiple Indications in Direct-to-Consumer Television 
Advertisements

OMB Control Number 0910-NEW

    Section 1701(a)(4) of the Public Health Service Act (42 U.S.C. 
300u(a)(4)) authorizes the FDA to conduct research relating to health 
information. Section 1003(d)(2)(C) of the Federal Food, Drug, and 
Cosmetic Act (FD&C Act) (21 U.S.C. 393(d)(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.
    The Office of Prescription Drug Promotion's (OPDP) mission is to 
protect the public health by helping to ensure that prescription drug 
promotion is truthful, balanced, and accurately communicated. OPDP's 
research program provides scientific evidence to help ensure that our 
policies related to prescription drug promotion will have the greatest 
benefit to public health.
    Toward that end, we have consistently conducted research to 
evaluate the aspects of prescription drug promotion that are most 
central to our mission, focusing in particular on three main topic 
areas: (1) Advertising features, including content and format; (2) 
target populations; and (3) research quality. Through the evaluation of 
advertising features, we assess how elements such as graphics, format, 
and disease and product characteristics impact the communication and

[[Page 12693]]

understanding of prescription drug risks and benefits. Focusing on 
target populations allows us to evaluate how understanding of 
prescription drug risks and benefits may vary as a function of 
audience, and our focus on research quality aims at maximizing the 
quality of research data through analytical methodology development and 
investigation of sampling and response issues. This study will inform 
the first topic area, advertising features, including content and 
format.
    Because we recognize the strength of data and the confidence in the 
robust nature of the findings is improved through the results of 
multiple converging studies, we continue to develop evidence to inform 
our thinking. We evaluate the results from our studies within the 
broader context of research and findings from other sources, and this 
larger body of knowledge collectively informs our policies as well as 
our research program. Our research is documented on our homepage, which 
can be found at: https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/office-prescription-drug-promotion-opdp-research. The 
website includes links to the latest Federal Register notices and peer-
reviewed publications produced by our office. The website maintains 
information on studies we have conducted, dating back to a direct-to-
consumer (DTC) survey conducted in 1999.
    A number of prescription drugs are approved for multiple 
indications. These indications can be similar in certain respects 
(e.g., diabetic peripheral neuropathy and fibromyalgia, which are both 
conditions that manifest in pain) or very different from one another 
(e.g., diabetic peripheral neuropathy and generalized anxiety 
disorder). If a drug is approved for multiple indications, sponsors 
choose whether to promote only one of those indications in DTC 
television advertising, or multiple indications in the same television 
advertisement. We are unaware of any quantitative research that 
addresses how presenting multiple indications in one advertisement 
affects consumers' processing of drug information. Some research 
suggests that presenting more than one indication in a television 
advertisement, regardless of the similarity of the indications, may 
increase the cognitive load on consumers, thus decreasing their 
understanding of the drug's indications (Refs. 1-3).
    When more than one indication is presented, the similarity or 
dissimilarity of the indications may affect participants' ability to 
remember and understand the indications. If this is the case, it is not 
clear whether similarity would have a positive or negative effect in 
the multimodal context of a television advertisement (e.g., Refs. 4 and 
5).
    This study will provide preliminary information on whether 
consumers face challenges when multiple indications are promoted in a 
single television advertisement. The study also will explore whether 
similarity of the indications affects participants' likelihood to 
recall and understand the indications, and whether its effect would be 
positive or negative.
    We propose to test three types of fictional DTC television 
advertisements--one that promotes a single indication, one that 
promotes an indication plus a similar indication, and one that promotes 
an indication plus a dissimilar indication--in two different medical 
conditions (table 1).

              Table 1--Study Design: 1 x 3 Factorial Experiment Repeated in Two Medical Conditions
----------------------------------------------------------------------------------------------------------------
                                                                    Indication 1 plus a     Indication 1 plus a
                                             Indication 1           similar indication    dissimilar  indication
----------------------------------------------------------------------------------------------------------------
Study 1: Diabetic peripheral          DPN.......................  DPN + fibromyalgia....  DPN + generalized
 neuropathy (DPN).                                                                         anxiety disorder.
Study 2: Rheumatoid arthritis (RA)..  RA........................  RA + psoriatic          RA + ulcerative
                                                                   arthritis.              colitis.
----------------------------------------------------------------------------------------------------------------

    We plan to conduct two pretests (one for each main study) and two 
main studies not longer than 20 minutes, administered via internet 
panel, to test the experimental manipulations and pilot the main study 
procedures. Participants will be randomly assigned to view one study 
advertisement and then complete a questionnaire that assesses recall 
and comprehension of the drug's benefits and risks, benefit and risk 
perceptions, attitudes, and behavioral intentions. We will also measure 
covariates such as demographics and health literacy. Taking into 
account prior research, it is our hypothesis that participants will be 
more likely to correctly recall and understand the first indication 
when it is presented alone, compared with when it is presented with a 
second (similar or dissimilar) indication. We will explore whether 
similarity of the indications affects participants' likelihood to 
recall and understand the indications. We will also explore the effects 
of the indication presentation on benefit and risk perceptions, 
attitudes toward the drug and the indication information, and 
intentions to look for more information and ask a doctor about the 
drug.
    For all phases of this research, we will recruit adult volunteers 
18 years of age or older. For Pretest 1 and Study 1, we will recruit 
participants who self-report being diagnosed with diabetes (N = 60 in 
Pretest 1 and N = 402 in Study 1). For Pretest 2 and Study 2, we will 
recruit participants who self-report being diagnosed with rheumatoid 
arthritis (N = 60 in Pretest 2 and N = 402 in Study 2). We will exclude 
individuals who work for the Department of Health and Human Services or 
work in the healthcare, marketing, or pharmaceutical industries. We 
will also exclude pretest participants from the main studies, and 
participants will not be able to participate in both Studies 1 and 2. 
With these sample sizes, we will have sufficient power to detect small-
sized effects in Studies 1 and 2. For the burden estimate, we include 
an additional 10% over our target number of valid completes to account 
for some overage.
    In the Federal Register of July 6, 2020 (85 FR 40296), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. FDA received four comments that were PRA-
related.
    Within the four submissions, FDA received multiple comments that 
the Agency has addressed below. For brevity, some public comments are 
paraphrased and therefore may not reflect the exact language used by 
the commenter. We assure commenters that the entirety of their comments 
was considered even if not fully captured by our paraphrasing in this 
document.
    (Comment) One comment suggested several ideas for other study 
designs, including: (1) Studying consumer reactions to actual 
advertisement campaigns; (2) studying consumer reactions to watching a 
DTC television advertisement and then viewing a related website; and 
(3) studying advertisements for multiple indications with different 
risk profiles. Another comment suggested another study idea:

[[Page 12694]]

Studying a drug with multiple indications for the same disease.
    (Response) We appreciate these alternate study ideas. As this is 
the first study on this topic, we acknowledge our study cannot answer 
every research question. We believe these alternate study ideas could 
be candidates for future research, and we encourage stakeholders to 
conduct research in this area.
    (Comment) One comment recommended using Crohn's or ulcerative 
colitis rather than leukemia as the dissimilar indication in Study 2 to 
avoid confusion with adverse effects of common RA medications.
    (Response) Based on this comment, we plan to use ulcerative colitis 
rather than leukemia as the dissimilar indication in Study 2.
    (Comment) Three comments noted that care should be taken to reduce 
confounding variables in the study stimuli in terms of length, order 
and presentation of indications, background and actor profiles, 
advertisement quality, and audio and visual effects.
    (Response) We can confirm that care has been taken to ensure that 
we do not have any unintentional confounds across the study conditions. 
The advertisements use the same actors, scenes, audio and visual 
effects and all other design and content features to ensure that all 
elements are consistent across experimental conditions. We also used 
the same setting, actors, and advertisement concept across Study 1 and 
Study 2 to minimize differences across the two studies. The only aspect 
that will change is the manipulated content (i.e., script and 
superimposed text relaying the indications).
    (Comment) One comment requested that we clarify how we are defining 
similar versus dissimilar indications.
    (Response) The similar indications have similar clinical 
manifestations: In Study 1, nerve-related pain for diabetic peripheral 
neuropathy and fibromyalgia, and in Study 2, joint pain for rheumatoid 
arthritis and psoriatic arthritis. The dissimilar indications have 
dissimilar clinical manifestations: In Study 1, nerve-related pain for 
diabetic peripheral neuropathy and anxiety for generalized anxiety 
disorder, and in Study 2, joint pain for rheumatoid arthritis and 
abdominal pain and diarrhea for ulcerative colitis.
    (Comment) One comment recommended stratification across conditions 
for demographics and several health characteristics.
    (Response) Typically, stratified randomization is used if there are 
prognostic variables that correlate with outcome measures and 
researchers are concerned about such factors not being evenly 
distributed across groups (Ref. 6). We have no reason to expect that 
the aforementioned factors would have a strong association with the 
outcome measures, nor do we have reason to believe that we will not 
achieve adequate balance of prognostic variables given the large sample 
size proposed for this study (Ref. 6). Random assignment will help to 
produce groups which are, on average, probabilistically similar to each 
other. Because randomization eliminates most other sources of 
systematic variation, we can be reasonably confident that any effect 
that is found is the result of the intervention and not some 
preexisting differences between the groups (Ref. 7). However, we have 
included questions about demographics and health characteristics, which 
will enable us to assess their association with our outcomes and 
statistically control for them if necessary.
    (Comment) One comment noted that the sample size per cell should be 
at least 75 participants.
    (Response) We conducted power analyses to determine sample size. We 
plan to have 134 participants per cell in each study, for a total of 
402 participants per study.
    (Comment) One comment noted that recruiting participants with only 
the primary indication could bias results because participants will be 
more familiar with their own medical condition. Instead, it suggested 
that for each study condition we recruit a sample that matches that 
study condition (e.g., recruiting participants with diabetic peripheral 
neuropathy or fibromyalgia for the second study condition in Study 1).
    (Response) We agree that participants may know more about their own 
medical condition than the other medical conditions advertised. 
However, we believe the alternate design offered in the comment would 
make results difficult to interpret as it would be unclear whether 
differences were due to the advertisement manipulations or to the 
different samples. Instead, we plan to keep the original design. We do 
not plan to compare participants' recall, recognition, or comprehension 
of the primary indication to the second indication (which may lead to 
the bias noted in the comment). Rather, we plan to compare 
understanding across the experimental conditions. For instance, we are 
testing the hypothesis that participants (with diabetes in Study 1 and 
rheumatoid arthritis in Study 2) who see the first indication alone 
will be more likely to recall, recognize, and comprehend the first 
indication compared with participants (with diabetes in Study 1 and 
rheumatoid arthritis in Study 2) who see the first indication and a 
second (similar or dissimilar) indication. As another example, we would 
expect that recall, recognition, and comprehension of the second 
indication would be higher when the second indication is mentioned in 
the advertisement compared with when it is not (e.g., participants are 
more likely to know the drug is also indicated for fibromyalgia when 
the advertisement mentions the fibromyalgia indication). We will 
measure participants' familiarity with treatments for each medical 
condition and assess whether they have been diagnosed with each medical 
condition. We can use these variables to explore differences among 
participants. A future study could examine how individuals suffering 
from fibromyalgia or generalized anxiety, or from psoriatic arthritis 
or ulcerative colitis (which are secondary indications in the current 
study) may interpret these advertisements.
    (Comment) One comment suggested recruiting participants with 
diabetic peripheral neuropathy specifically rather than diabetes in 
Study 1, while another comment noted that diabetic peripheral 
neuropathy is underdiagnosed and therefore may present recruitment 
challenges.
    (Response) We plan to retain the diabetes sample for Study 1 to aid 
recruitment. We will ask participants if they experience diabetes-
related pain and whether they have been diagnosed with diabetic 
peripheral neuropathy.
    (Comment) One comment noted concern about the chosen indications 
because medical conditions can differ from one another in several ways 
(e.g., prevalence, treatment options) and suggested considering public 
awareness of the medical conditions.
    (Response) We agree that medical conditions vary; this is 
unavoidable in a study of this kind. To account for this, we plan to 
conduct two studies using different medical conditions to determine 
whether the effects replicate across studies. We will measure 
participants' familiarity with treatments for the medical conditions in 
each study.
    (Comment) One comment suggested asking participants if they were 
familiar with the fictitious drug and terminating participants who say 
yes.
    (Response) It is unlikely that many participants will claim to be 
familiar with the fictional brand name. However, past research has 
noted the human tendency to falsely recognize content

[[Page 12695]]

(Ref. 8). While theoretically interesting, the fact that people may 
falsely recognize our brand should not threaten the internal validity 
of the current study. Random assignment should guard against systematic 
differences among groups in terms of false recognition tendency. 
Nonetheless, we appreciate this concern and in response, we have added 
a question to the survey to measure familiarity with the brand, which 
we can then explore in auxiliary analyses, but we do not think 
participants with false brand familiarity should be removed from the 
study. Our study sample includes those with rheumatoid arthritis for 
one of the studies (a condition with lower prevalence in the United 
States, about 0.6 percent of the population). Excluding those with 
false recognition would impose additional burden on recruitment.
    (Comment) One comment suggested that the questionnaire should 
include the statement ``Based on the ad you just saw . . .'' before 
each question.
    (Response) We include this statement and similar language 
throughout the questionnaire.
    (Comment) One comment suggested we measure unaided awareness of the 
indications, aided awareness of the indications, likelihood to go to 
the branded drug website to learn more about the drug, and likelihood 
to ask their doctor about the drug.
    (Response) We measure unaided awareness of the indications (benefit 
recall) in Question 2, aided awareness of the indications (benefit 
recognition) in Question 3, and likelihood to look for more information 
about the drug and ask their doctor about the drug in Questions 16 and 
17.
    (Comment) One comment suggested deleting Questions 2 and 13 in 
favor of Questions 3 and 14 because these open-ended questions may be 
difficult for respondents to answer.
    (Response) Questions 2 and 13 measure unaided recall of drug 
benefits and risks whereas Questions 3 and 14 measure recognition of 
drug benefits and risks. We agree that recall is more difficult than 
recognition. We plan to retain Questions 2 and 13 but will assess their 
utility in cognitive interviews and pretesting.
    (Comment) One comment suggested using consistent scales on the 
questionnaire.
    (Response) Most questionnaire items have true/false/don't know or 
yes/no/don't know response options. Some items are validated measures 
with Likert-type scales; for these, we have used the response options 
from the validated measures.
    (Comment) Two comments suggested removing or revising questions 7-
10 because participants do not have the medical expertise to say 
whether someone is a good candidate for a drug. Instead, the comments 
suggested asking whether the drug is appropriate for them.
    (Response) These questions are intended to measure participants' 
comprehension of the indications as communicated in the advertisements. 
DTC advertisements can drive consumers to ask their doctors about a 
drug, so it is important to know whether the drug indication is 
accurately communicated to consumers. We used similar questions about 
being a ``good candidate'' in another study (OMB control number 0910-
0885). In cognitive interviews, participants were able to answer the 
questions and they understood that the questions were asking about the 
drug information in the advertisement. We also tested language, such as 
whether it would be appropriate for the person to ask their doctor 
about the drug, but participants found this language to be wordy and 
unnecessary. We do not plan to change these questions at this time, but 
we will assess participants' ability to answer these questions in 
cognitive interviews and pretesting.
    (Comment) Two comments suggested deleting or revising several items 
(Questions 16, 17, 21-24, 26, 27 in one comment, Questions 18-27 in the 
other) because responses to these items may be influenced by the 
particular stimuli used and by factors other than those being studied.
    (Response) These items measure intentions, attitudes, and 
perceptions. We agree that several factors can influence these 
outcomes. However, random assignment to conditions allows us to 
determine whether the experimental manipulation is responsible for 
differences in these outcomes across conditions. We will retain these 
items and assess their utility in cognitive interviews and pretesting.
    (Comment) One comment suggested combining Questions 30 through 33 
into one item and asking it at the beginning of the questionnaire.
    (Response) We combined questions Q31 and Q32 into one item and 
moved the item to the screener.
    (Comment) One comment suggested we ask participants if they have 
been diagnosed with the indicated medical conditions (diabetic 
neuropathy, fibromyalgia, etc.).
    (Response) These questions are included on the questionnaire.
    FDA estimates the burden of this collection of information as 
follows:

                                                     Table 2--Estimated Annual Reporting Burden \1\
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                                                                 Number of
                  Activity                       Number of     responses per   Total annual           Average burden per response           Total hours
                                                respondents     respondent      respondents
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Pretest 1 and 2 screener....................             264               1             264  0.083 (5 minutes).........................              22
Pretest 1 and 2.............................             132               1             132  0.333 (20 minutes)........................              44
Main Study 1 and 2 screener.................           1,770               1           1,770  0.083 (5 minutes).........................             147
Main Study 1 and 2..........................             885               1             885  0.333 (20 minutes)........................             295
                                             -----------------------------------------------------------------------------------------------------------
    Total...................................  ..............  ..............  ..............  ..........................................             508
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

References

    The following references are on display at the Dockets Management 
Staff (see ADDRESSES) and are available for viewing by interested 
persons between 9 a.m. and 4 p.m., Monday through Friday; these are not 
available electronically at https://www.regulations.gov as these 
references are copyright protected. Some may be available at the 
website address, if listed. FDA has verified the website addresses, as 
of the date this document publishes in the Federal Register, but 
websites are subject to change over time.

1. Mayer, R.E. and R. Moreno (2003), ``Nine Ways to Reduce Cognitive 
Load in Multimedia Learning.'' Educational Psychologist, 38(1), 43-
52.
2. Mutlu-Bayraktar, D., V. Cosgun, and T.

[[Page 12696]]

Altan (2019), ``Cognitive Load in Multimedia Learning Environments: 
A Systematic Review.'' Computers & Education, 141, 103618.
3. Betts, K.R., V. Boudewyns, K.J. Aikin, C. Squire, et al. (2018), 
``Serious and Actionable Risks, Plus Disclosure: Investigating an 
Alternative Approach for Presenting Risk Information in Prescription 
Drug Television Advertisements.'' Research in Social and 
Administrative Pharmacy, 14(10), 951-963.
4. Jiang, Y.V., H.J. Lee, A. Asaad, and R. Remington (2016), 
``Similarity Effects in Visual Working Memory.'' Psychonomic 
Bulletin & Review, 23(2), 476-482.
5. Oberauer, K. and E.B. Lange (2008), ``Interference in Verbal 
Working Memory: Distinguishing Similarity-Based Confusion, Feature 
Overwriting, and Feature Migration.'' Journal of Memory and 
Language, 58(3), 730-745.
6. Friedman, L.M., C.D. Furberg, and D.L. DeMets (1998), 
Fundamentals of Clinical Trials. New York, NY: Spring Science-
Business Media, LLC.
7. Fisher, R.A. (1937), The Design of Experiments. Edinburgh, United 
Kingdom: Oliver and Boyd.
8. Southwell, B.G. and R. Langteau (2008), ``Age, Memory Changes, 
and the Varying Utility of Recognition as a Media Effects Pathway''. 
Communication Methods and Measures, 2, 100-114.

    Dated: February 26, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2021-04472 Filed 3-3-21; 8:45 am]
BILLING CODE 4164-01-P


