[Federal Register Volume 83, Number 154 (Thursday, August 9, 2018)]
[Notices]
[Pages 39441-39448]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-17045]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2017-N-0558]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Disclosures in 
Professional and Consumer Prescription Drug Promotion

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 (PRA).

DATES: Fax written comments on the collection of information by 
September 10, 2018.

ADDRESSES: To ensure that comments on the information collection are 
received, OMB recommends that written comments be faxed to the Office 
of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer, 
Fax: 202-395-7285, or emailed to [email protected]. All 
comments should be identified with the OMB control number 0910-NEW and 
title ``Disclosures in Professional and Consumer Prescription Drug 
Promotion.'' 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, 
[email protected].

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.

Disclosures in Professional and Consumer Prescription Drug Promotion

OMB Control Number 0910-NEW

I. Background

    Section 1701(a)(4) of the Public Health Service Act (42 U.S.C. 
300u(a)(4)) authorizes FDA to conduct research relating to health 
information. Section 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.
    FDA regulates prescription drug advertising and promotional 
labeling directed to healthcare professionals (HCPs) and consumers 
(section 502(a) and (n), respectively, of the FD&C Act (21 U.S.C. 
352(a) and (n))). In the course of promoting their products, 
pharmaceutical sponsors (sponsors) may present a variety of information 
including the indication, details about the administration of the 
product, efficacy information, and clinical trial data. To present 
often complicated information concisely, sponsors may not include 
relevant information in the body of the text or visual display of the 
claim. Additionally, sponsors may not always present limitations to the 
claim in the main body of the text or display. In these cases, sponsors 
typically include disclosures of information somewhere in the 
promotional piece.
    There is limited published research on disclosures in prescription 
drug promotion, either directed to consumers or to HCPs. The use of 
disclosures is one method of communicating information to HCPs and 
consumers about scientific and clinical data, the limitations of that 
data, and practical utility of that information. These disclosures may 
influence HCP and consumer comprehension and decision making, and may 
affect how and what treatment HCPs prescribe for their patients. 
Previous research on the effectiveness of disclosures has been 
conducted primarily in the dietary supplement arena (Refs. 1-4). Thus, 
the proposed research will examine the effectiveness of clear and 
conspicuous disclosures in prescription drug promotion directed to both 
populations. The purpose of our study is to determine how useful 
disclosures regarding prescription drug information are when presented 
prominently and adjacent to claims.\1\ Specifically, are HCPs and 
consumers able to use disclosures to effectively frame information in 
efficacy claims in prescription drug promotion?
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    \1\ The Federal Trade Commission (FTC), which regulates the 
advertising of non-prescription drug products as well as other non-
FDA regulated products (e.g., package goods, cars, etc.) issued a 
specific position on disclosures (Ref. 5) for the advertising it 
regulates. Specifically, FTC explains that disclosures must be 
``clear and conspicuous''; in other words, in understandable 
language, located near the claim to be further clarified, and not 
hidden or minimized by small font or other distractions.
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    To address this research question, we have designed a set of 
studies that cover both consumers and HCPs, as well as three 
presentations addressing different

[[Page 39442]]

types of information: Scope of treatment, ease of use, and statistical 
significance (see table 1). The scope of treatment information to be 
tested can be thought of as disease-awareness information; that is, a 
broader discussion of a medical condition that includes disease 
characteristics beyond what the promoted drug has been shown to treat. 
The disclosure for this condition will focus on the disease 
characteristics that the product has been shown to treat. The ease of 
use information to be tested is a simple claim of easy drug 
administration, followed by a disclosure that includes material 
information about drug administration. Finally, the statistical 
significance information to be tested includes a presentation of 
efficacy analyses, followed by a disclosure revealing that the results 
of the presented analyses were not statistically significant, and thus 
must be viewed with considerable caution. We selected these types of 
information because they are commonly seen in promotional material.
    Each participant will view three different professionally developed 
mock promotional print pieces for different prescription drug products 
that mimic currently available promotion. For each of the three 
promotional pieces, they will be randomized to see an ad with a weak 
disclosure, a strong disclosure, or no disclosure. We will manipulate 
the strength of disclosure by including additional concluding 
information (strong) or not (weak) in the disclosure statement. In all 
cases, disclosures will be adjacent to claims and written in font clear 
enough to be detected.

                       Table 12--Identical Study Designs for Samples of HCPs and Consumers
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                                                      Level of disclosure
            Type of claim             --------------------------------------------------         Control
                                                 Weak                    Strong
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                                                  Study A: HCPs
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Scope of Treatment...................  Evidence Only..........  Evidence + Conclusion..  No Disclosure
Ease of Use..........................  Evidence Only..........  Evidence + Conclusion..  No Disclosure
Statistical Significance.............  Evidence Only..........  Evidence + Conclusion..  No Disclosure
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                                               Study B: Consumers
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Scope of Treatment...................  Evidence Only..........  Evidence + Conclusion..  No Disclosure
Ease of Use..........................  Evidence Only..........  Evidence + Conclusion..  No Disclosure
Statistical Significance.............  Evidence Only..........  Evidence + Conclusion..  No Disclosure
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    We will analyze the results of the scope of treatment disclosures, 
the ease of use disclosures, and the statistical significance 
disclosures independently of each other, even though each participant 
will see one of each. The claims and disclosures are different enough 
that practice effects should be moderated, but we will counterbalance 
the order of ads shown to minimize potential bias.
    Because promotional pieces intended for HCPs and consumers have 
different levels of complexity and medical depth, and because the 
amount of knowledge expected between the two groups differs, the 
studies will use separate mock promotional pieces and ask slightly 
different comprehension questions of each group. We will maintain as 
much similarity across groups as possible for descriptive comparisons.
    Both consumers and HCPs will be recruited from internet panels. 
Because promotional pieces will represent three different medical 
conditions, we will obtain a general population sample of consumers and 
a HCP sample of primary care physicians. We will exclude individuals 
who are employees of the U.S. Department of Health and Human Services 
or who work in pharmaceutical, advertising, or marketing settings 
because their knowledge and experiences may not reflect those of the 
typical healthcare provider or consumer. Eligible participants who 
agree to participate voluntarily in this survey will view mock 
promotional pieces and answer questions about their comprehension of 
the main messages in the promotion, perceptions of the product, 
attention to disclosures and intention to ask a HCP about it 
(consumers) or to prescribe the product (HCPs). Questionnaires are 
available upon request.
    Pretests will be conducted before conducting the main studies to 
ensure the mock promotional pieces are realistic and that the 
questionnaire flows well and questions are reasonable. We will 
supplement the findings of the pretests with two small eye-tracking 
studies. Researchers use eye-tracking technology to capture viewing 
behavior that is independent of self-report. The technology measures 
where and for how long participants glanced at or examined particular 
parts of a display. It has been used in studies of consumer print 
advertising (Refs. 6-8) and internet promotion (Refs. 9 and 10). To our 
knowledge, there is little or no published research using eye-tracking 
technology with HCPs.
    We will use these small eye-tracking studies to determine what 
parts of each promotional piece consumers and HCPs actually viewed. 
Specifically, we will be able to determine whether they looked at the 
disclosure statement at all, and we can obtain a rough idea of how long 
they looked at it. This data will complement the self-reported items on 
the questionnaire. Moreover, we will use this data, as well as the 
pretest data, to improve the main studies. For this part of the study, 
20 consumers and 20 HCPs will view the promotional pieces.
    In the Federal Register of June 14, 2017 (82 FR 27268), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. Four comments were received. Responses to 
those comments follow. 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. The following acronyms are used here: DTC = direct-to-
consumer; HCP = healthcare professional; FDA and ``The Agency'' = Food 
and Drug Administration; OPDP = FDA's Office of Prescription Drug 
Promotion.
    The first public comment responder (regulations.gov tracking number 
lkl-8y39-rtyb) included 25 individual

[[Page 39443]]

comments, to which we have responded.
    Comment 1a (summarized): FDA is conducting too much research 
without articulating a clear, overarching research agenda or adequate 
rationales on how the proposed research related to the goal of further 
protecting public health. The Agency should publish a comprehensive 
list of its prescription drug advertising and promotion studies from 
the past 5 years and articulate a clear vision for its research 
priorities for the near future.
    Response 1a: OPDP's mission is to protect the public health by 
helping to ensure that prescription drug information is truthful, 
balanced, and accurately communicated, so that patients and healthcare 
providers can make informed decisions about treatment options. OPDP's 
research program supports this mission by generating 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 we believe are most central to our 
mission, focusing in particular on three main topic areas: Advertising 
features, including content and format; target populations; and 
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 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.
    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/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cder/ucm090276.htm. 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 survey of DTC attitudes 
and behaviors conducted in 1999.
    Comment 1b (The commenter provided a summary of the comments 
followed by a more detailed description of the same comments. For 
brevity, the summary of comments has been omitted and only the specific 
comments [1b through 1y] are provided below. The commenter's full 
comments may be accessed at regulations.gov via tracking number lkl-
8y39-rtb) (verbatim): It is not clear from this description whether the 
study will yield useful information to evaluate whether disclosures 
provide appropriate contextual information in certain communications, 
whether such disclosures can be made more effective, and where the 
disclosures are necessary to ensure communications are truthful and 
non-misleading. The Agency should provide significantly more detail 
regarding the design of the study, the proposed disclosures, the mock 
promotional pieces, and the information it seeks to collect.
    Response 1b: We have provided the purpose of the study, the design, 
the population of interest, and have provided the questionnaire to 
numerous individuals upon request. These materials have proven 
sufficient for others to comment publicly, and for academic experts to 
peer-review the study successfully. We do not make draft stimuli public 
during this time because of concerns that this may contaminate our 
participant pool and compromise the research.
    Comment 1c (summarized): After pretesting, the Agency should make 
available revised questionnaires, data collection methodologies, and 
stimuli.
    Response 1c: In this current notice, we provide the revised design 
as based on academic peer reviewers, cognitive interviewing, and public 
comments. The revised questionnaire is also available upon request. Our 
full stimuli are under development during the PRA process. We do not 
make draft stimuli public during this time because of concerns that 
this may contaminate our participant pool and compromise the research. 
Individuals are welcome to inquire about the progress of the study and 
any changes from the pretests will be communicated at that time.
    Comment 1d (summarized): FDA should base mock promotional stimuli 
on realistic promotional pieces.
    Response 1d: We have done this. Our stimuli are modified from 
actual promotional pieces in the marketplace to disguise the original 
product.
    Comment 1e (summarized): It is unclear whether such disclosures 
will contain relevant information ordinarily provided in promotional 
materials.
    Response 1e: The goal of our research is to obtain answers to 
questions about prescription drug promotion that will inform the Agency 
and stakeholders. Thus, we strive in all of our studies to make our 
mock promotional pieces as realistic as possible. That includes any 
disclosures that we may include in testing. Also, please see response 
to comment 1d.
    Comment 1f (verbatim): FDA seems to have an overly broad conception 
of the need for disclosures for ``scope of treatment'' communications. 
In the Notice, FDA describes this type of communication as ``a disease-
awareness claim; that is, a broader discussion of a medical condition 
that may include disease characteristics beyond what the promoted drug 
has been shown to treat.'' Where a disease awareness communication 
discusses a disease in a manner beyond what the promoted drug has been 
shown to treat, but does so in a balanced manner without implying any 
particular treatment benefits from the associated drug, it should be 
viewed as providing helpful general background information on the 
disease, and not as making an off-label claim for the drug. In those 
circumstances, there should be no need for any disclosure about the 
limits of use of the drug. FDA should clarify its understanding of 
``scope of treatment'' claims and make its proposed claims and 
disclosures available for public comment.
    Response 1f: Previous research has demonstrated that presenting 
study participants with information about the consequences of a 
disease, particularly when the information was integrated into one 
print ad with information about a particular drug, resulted in false 
beliefs that the advertised drug prevented those consequences.\2\ The 
``scope of treatment'' claims that are included in this research are 
embedded in mock promotional materials, juxtaposed with specific 
efficacy information about the mock drug products. As such, they will 
likely imply ``particular treatment benefits from the associated 
drug.'' This research will help us to evaluate the usefulness of a 
disclosure in relation to this type of information when it is found in 
promotional pieces. Also, please see response to comment 1c.
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    \2\ Aikin, K.J., H.W. Sullivan, and K.R. Betts, (2016). 
``Disease information in direct-to-consumer prescription drug print 
ads.'' Journal of Health Communication, 21(2), pp. 228-239.

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    Comment 1g (verbatim): FDA states that the ``ease of use'' claim 
``is a simple claim of easy drug administration that omits specific 
important details that contribute to a more difficult drug 
administration than suggested.'' This statement appears to imply that 
all ease of use claims are misleading, where the Agency perhaps intends 
to clarify that validated and non-misleading ``ease of use'' claims may 
require a disclosure or more context. FDA should clarify its 
understanding of ``ease of use'' claims, and, in testing, ensure it 
does not test overly misleading base claims for ``ease of use'' that 
would be difficult to contextualize with a disclosure statement and 
hence would bias the results of its study. Such claims should be made 
available for public comment.
    Response 1g: FDA did not intend to imply that all ease of use 
claims are misleading or that all ease of use claims would necessarily 
require a disclosure. FDA agrees that some ease of use statements 
require a disclosure or more context and intends to evaluate one such 
example with this research. We have revised the description of the 
study in this notice to clarify. Also, please see response to comment 
1c.
    Comment 1h (verbatim): FDA states that the ``statistical 
significance'' claim ``will be one in which the disclosure reveals that 
the presented analyses were not statistically significant, and thus 
must be viewed with considerable caution.'' It is not clear what 
content FDA intends to test for this type of claim. We encourage FDA to 
clarify how it intends to present ``not statistically significant'' 
analyses for testing in order to ensure such claims are presented with 
appropriate contextual information. Such claims should be made 
available for public comment.
    Response 1h: Please see responses to comment 1c, 1d, and 1e.
    Comment 1i (summarized): The Agency should clarify what 
distinctions will be made between HCP and consumer pieces.
    Response 1i: As our mock promotional pieces have been adapted from 
existing materials in the public domain, the materials directed to HCPs 
and to consumers vary in similar ways to what can currently be seen in 
the public domain. For example, materials directed to HCPs tend to have 
more data, more technical medical language, and more text in general. 
Consumer pieces are generally written in plainer language and generally 
do not include as much data and statistical information. Our pieces are 
highly realistic as they were developed from actual promotional pieces.
    Comment 1j (verbatim): The Agency proposes that consumer and HCP 
subjects will be recruited from internet panels, indicating that the 
study will be conducted using an electronic format. Because the 
proposed research topic is not dependent on an electronic medium, FDA 
should consider testing non-electronic media as well, including printed 
promotional pieces.
    Response 1j: Although our study will be conducted via the internet, 
we will show participants mock print materials in .pdf format.
    Comment 1k (verbatim): The Agency proposes to use eye-tracking 
studies to complement the self-reported items on the questionnaire and 
to improve the main studies. [The commenter] encourages the Agency to 
use this technology in conjunction with other inputs (for example, 
qualitative research) to understand why subjects are looking at a 
portion of the proposed materials, rather than to draw conclusions that 
such portions were viewed. Additionally, an explanation of the use of 
eye-tracking technology should also be included during the subject 
enrollment process.
    Response 1k: FDA plans to collect and analyze eye-tracking 
(physical measures of attention) data in conjunction with other 
measures, including cognitive interviews. To avoid the potential for 
priming effects, the eye-tracking component of the study will not be 
explained to recruited individuals before they report for their in-
person sessions. However, participants will be made aware of the eye-
tracking component during the informed consent process.
    Comment 1l (summarized): The commenter recommends increasing the 
sample size of the eye-tracking components to ensure more robust data.
    Response 1l: Our primary method of analysis of the eye-tracking 
data will be examination of gaze plots coupled with self-report data 
provided by participants. Thus, eye-tracking results will be examined 
on an individual, rather than aggregate, level. Furthermore, the eye-
tracking studies included in this research are intended as qualitative, 
formative studies; they will be used to inform any necessary changes to 
the stimuli before the main studies. Formative eye-tracking studies 
such as these are often executed with sample sizes as small as five 
participants.\3\ In our experience, a sample of 20 participants in each 
population ensures that we will collect fully useable data from a 
minimum of 15 participants in each population. Used as an observation 
tool, eye-tracking complements the other data collected to increase 
discoverability of specific events and confidence in our qualitative 
findings.
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    \3\ Pernice, K. and J. Nielsen, (2009). ``How to Conduct 
Eyetracking Studies.'' https://media.nngroup.com/media/reports/free/How_to_Conduct_Eyetracking_Studies.pdf.
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    Comment 1m (summarized): The commenter recommends limiting the 
participant sample to disease sufferers rather than a general 
population sample.
    Response 1m: We carefully consider the type of sample to use in 
each of our studies. In the current study, the population of sufferers 
for the conditions addressed by our stimuli (i.e., chronic obstructive 
pulmonary disease (COPD), chronic iron overload, and high blood 
pressure) are varied. Because we are showing participants more than one 
ad, we chose not to select diagnosed populations or specialists.
    Comment 1n (summarized): FDA should recruit a demographically and 
geographically diverse sample.
    Response 1n: We agree and we plan to recruit individuals with a 
range of gender, race, ethnicity, and, as much as possible within an 
internet sample, socioeconomic status. For the consumer sample, we aim 
for a sample with 60 percent of people who have some college or less. 
An advantage of sampling via internet panel is that we have access to 
individuals in all parts of the United States.
    Comment 1o (verbatim): FDA should capture whether subjects 
comprehend certain information disclosed in the mock promotional 
pieces, even if the subject does not recall information on the 
specifics. Currently, open-ended and recall questions (e.g., Consumer 
Questionnaire Q2-Q3; HCP Questionnaire Q2-Q3) ask test subjects to 
identify certain information regarding the featured drug products (what 
a mock drug product is specifically ``used for'' or ``not approved 
for''). It is not clear why such an open-ended format or questions are 
necessary for the research purpose of the study, as subjects could 
recognize a limit to the efficacy being presented even if they do not 
follow or recall all of the details of a disclosure.
    Response 1o: We do intend to capture what information has been 
observed in the mock promotional pieces, and we do this through the 
open-ended and recall questions. It is common practice to include open-
ended and closed-ended questions in one research study, as they tend to 
complement each other. Open-ended questions allow responses that have 
not been prompted by particulars, which is not the case with closed-
ended questions. Closed-ended questions

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provide a more efficient way of obtaining information.
    Comment 1p (summarized): FDA should ensure that terms used in the 
consumer pieces are consumer-friendly.
    Response 1p: We agree and always review our mock consumer pieces 
for lay language. The terms mentioned by the commenter (e.g., chronic 
iron overload, COPD, lung function, scientific evidence, effectiveness, 
statistically significant) will be used in the HCP materials. However, 
we also strive to make our materials as realistic as possible, and in 
this case, we have modified existing DTC pieces for consumers. If they 
used a term (e.g., COPD), and OPDP reviewers agreed that this is common 
and acceptable, we maintained it in our mock pieces.
    Comment 1q (summarized): FDA should consider changing the sliding 
scale format of Q4.
    Response 1q: We carefully develop each question of our 
questionnaires, taking into account language and response options. No 
cognitive interview participant reported confusion with this sliding 
scale question. Without scientific justification for changing the 
response format of this question, we will maintain the current format.
    Comment 1r (verbatim): In a study setting, subjects may be prone to 
pay attention to more or all of the information presented throughout 
the study, including claims designed to be intentionally misleading. As 
a result, subjects are more likely to be biased based on the strength 
or weakness of the claims and disclosures presented. The Agency should 
address what efforts it will take to avoid response bias by presenting 
these varying degrees of disclosures.
    Response 1r: The study is designed so that participant will be 
randomly assigned to condition. Moreover, the only aspect of the 
participants' experiences that will be varied in the study will be the 
manipulations that we have described. Any individual differences in 
attention or ability or potential biases should be spread across 
experimental conditions. Thus, if we find differences between and among 
conditions, we can be reasonably sure that the manipulations caused the 
differences. We have not found in the past that our participants spend 
an inordinate amount of time viewing stimuli, but we will be careful to 
place the research in context when we interpret the data.
    Comment 1s (verbatim): The Consent Text introduction should not 
state that the survey is being conducted ``on behalf of the U.S. Food 
and Drug Administration.'' This statement could potentially influence 
subjects' responses to study questions. Instead, this information might 
be provided at the conclusion of the study.
    Response 1s: In previous studies, we took this same view and 
typically used ``Department of Health and Human Services.'' We will 
incorporate this change.
    Comment 1t (verbatim): Questions regarding statements in ads 
(Consumer Questionnaire Q10, Q20, Q30; HCP Questionnaire Q12, Q22, Q33) 
should be the first questions presented following the subjects' viewing 
of a promotional piece. A subject will likely recall the statements 
that appeared in the promotional piece most accurately immediately 
after reviewing the piece and before answering other questions that 
could influence their selection of answers.
    Response 1t: As with all other aspects of study design, we 
carefully develop questionnaires with order effects in mind. Therefore, 
we chose to include questions regarding perception of efficacy or ease 
of use, information seeking, and behavioral intention first because it 
is important that participant responses to these items be based solely 
on the information presented in the ads. The questions referenced by 
the commenter also include incorrect recall items, which could 
potentially bias responses to later questions if the order was changed. 
Additionally, repeated exposures to the correct recall items in the 
above-referenced questions could have a reinforcing effect that could 
confound results.
    Comment 1u (verbatim): In the Consumer Questionnaire, an ``FDA 
employee'' category, similar to S7 and S8, should be added to the 
Screener Survey. These individuals should also be terminated from the 
study.
    Response 1u: We will revise question S8 to read, ``Do you work for 
a pharmaceutical company, an advertising agency, a market research 
company, or the U.S. Department of Health and Human Services?'' to 
capture these individuals, as suggested.
    Comment 1v (verbatim): In the Consumer Questionnaire, Q8-Q9 should 
be presented prior to Q6-Q7 in order to prevent bias in favor of non-
HCP sources. Similarly, Q19 should appear before Q18, and Q28 should 
appear before Q27.
    Response 1v: We will reorder the questionnaire as the commenter 
suggested.
    Comment 1w (summarized): We recommend that Q8-Q9, Q19, and Q28 be 
expanded to more fully evaluate the role of the prescriber in aiding 
consumers' understanding of disclaimers in promotional materials.
    Response 1w: HCPs are often a very important source of information 
about prescription drugs. However, when prescription drugs are promoted 
directly to consumers, they may be more likely to look for information 
on their own before taking steps to consult their HCPs. We have taken 
this into account in this study by examining the responses of both 
consumers and HCPs.
    Comment 1x (verbatim): In the HCP Questionnaire, Q5, Q7, and Q29 
should be omitted. Comparative efficacy is highly dependent on the 
particular HCP subject's experience outside the experiment setting; 
this question thus may lead to highly variable results. Further, how 
the drug featured in the mock promotional communication compares to 
other prescription medications has no relevance to FDA's stated study 
goals. Questions regarding comparative efficacy should thus be omitted 
from the proposed HCP Questionnaire.
    Response 1x: Comparative efficacy questions are another way to 
assess how HCPs respond to prescription drug promotion. Any subjective 
experiences outside the experiment setting should fall out because HCPs 
will be randomly assigned to conditions. The questions are relevant to 
our study because HCPs make comparative decisions each time they make a 
prescribing decision.
    Comment 1y (verbatim): In the HCP Questionnaire, Q34 does not 
appear to provide appropriate programming instructions for the scenario 
in which Q33_A=01 and Q33_D=01. FDA should confirm that Q33 may be 
asked if subjects select both Q33_A and Q33_D, and provide that this 
question may be repeated for both responses. The variable label text 
for Q34 should also be rewritten as follows: ``How much did the 
statement [disclosure] influence your assessment of the scientific 
evidence for [D]esyflux?''
    Response 1y: Q33 asks whether participants have seen any of the 
listed statements. Q34 is asked for each of Q33_A and Q33_D when they 
respond affirmatively to that statement in Q33. Thus, participants who 
chose option 01 for both items will see two separate questions. We will 
make the suggested changes to Q34.
    The second public comment responder (regulations.gov tracking 
number lkl-8y11-169c) included four individual comments, to which we 
have responded.
    Comment 2a (summarized): FDA should give consideration to the 
representativeness of online study

[[Page 39446]]

volunteers to the general public who will view print ads.
    Response 2a: This is an excellent point and one to which we have 
given much thought. As with all research, there is a tradeoff of 
efficiencies when it comes to collecting information from volunteers. 
Recruiting from internet panels is a relatively economical way to 
achieve large sample sizes from all across the United States, making it 
possible to achieve geographic and urban/rural diversity in a way that 
was not previously possible. However, it is true that members of lower 
socioeconomic classes do not have the same access to computers and the 
internet, and therefore our sample may be skewed toward individuals who 
have higher education and/or income. We have attempted to mitigate this 
issue by aiming for recruitment of 60 percent of individuals with some 
or no college and 40 percent of individuals with a college degree or 
more.
    While it is important to note that random assignment of respondents 
to experimental conditions provides us the ability to make causal 
claims about our findings, we do note that truncating the population 
from which we sample is a limitation of the study and will describe 
this in any publication or presentation that results from the data.
    Comment 2b (verbatim): We suggest that the study include electronic 
advertisements in addition to print advertisements to account for and 
reflect changes in consumer consumption of media, including the 
increase of electronic promotion and advertising of products by 
sponsors.
    Response 2b: We agree that more information and promotion is moving 
to electronic presentations, including the internet, mobile 
applications, and other communication formats. However, the questions 
we ask in this current study are fundamental questions that should not 
differ based on presentation format. Moreover, our print ads are 
similar to what might be shown on a website, which is a prominent 
electronic format. We have other studies ongoing that are examining 
other electronic presentation modes (e.g., 82 FR 32842, July 18, 2017).
    Comment 2c (summarized): If the three levels of disclosure are to 
be strong, weak, and none, we recommend considering the following 
levels of disclosure:

 Additional concluding information makes it strong
 Less additional information makes it weak
 No additional information makes it none

    Response 2c: Thank you for clearly investing time and energy in 
responding to this study design. The suggested levels of disclosure are 
effectively the same as what we have included in our study design. The 
weak disclosure provides some additional information, while the strong 
disclosure provides both the additional information and an explicit 
conclusion based on the information.
    Comment 2d (summarized): FDA should keep in mind that stronger 
disclosures may be longer, therefore eye-tracking time may reflect 
length, not necessarily effectiveness.
    Response 2d: The commenter is correct in that a longer block of 
text will generally result in a longer gaze fixation. We have taken 
steps to keep the stronger disclosures as close as possible in length 
to the weaker disclosures. However, as noted previously, eye-tracking 
outcomes will be analyzed qualitatively. Our primary interest is 
whether the disclosure was attended to--the length of attention is of 
less interest in this case.
    The third public comment responder (regulations.gov tracking number 
lkl-8y16-bf58) included five individual comments, to which we have 
responded.
    Comment 3a (summarized): The commenter assumes that stimuli will 
conform to FDA regulations and requirements in non-study aspects and 
will not overdramatize claims versus disclosures.
    Response 3a: All stimuli will conform to FDA regulations, as 
reviewed by OPDP reviewers. Additionally, we have designed the 
materials to fall within realistic parameters, thus the claims and 
disclosures are representative of what we may see in the marketplace.
    Comment 3b (summarized): The commenter includes a section titled 
``Comments on the Brief Summary and Provision of Risk Information in 
Advertising'' wherein FDA is encouraged to continue to consider the 
purpose and practical limits of advertising.
    Response 3b: FDA agrees that a consideration of the purpose and 
practical limits of prescription drug promotion will guide the 
development of research projects. Otherwise, the comment appears to 
fall outside the scope of this particular proposed research.
    Comment 3c (summarized): Add ``Don't Know'' options for questions 
about perceived effectiveness in the consumer questionnaire.
    Response 3c: Questions about perceived effectiveness by definition 
involve subjective rather than objective assessments of effectiveness. 
Participants have the option to skip these questions if they wish.
    Comment 3d (verbatim): We suggest also including questions to 
capture whether respondents have a general understanding that there are 
limitations to the data and information being presented, even if they 
do not recall specific information and disclosure statements.
    Response 3d: This is a good suggestion, but it is important to 
phrase such questions appropriately. For example, simply asking 
participants if they believe the data is thorough and complete or that 
the data has limitations is not likely to yield useful information. 
However, there are several validated skepticism scales that approach 
this idea of trusting the validity of presented information. Although 
these items are not tied to data specifically, they will provide some 
information for us about how much individuals rely on the data. We have 
added two questions near the end of the survey to address this issue.
    Comment 3e (summarized): The commenter recommends deleting ``. . . 
from a source other than your healthcare provider'' from questions 6 
and 7.
    Response 3e: Because we ask about seeking information from a HCP in 
other questions, we will retain this distinction in Q6 and Q7 for 
clarity.
    The fourth public comment responder (regulations.gov tracking 
number lkl-8y38-n0p8) included eight individual comments, to which we 
have responded.
    Comment 4a (summarized): The commenter is supportive of the 
research.
    Response 4a: Thank you for your support.
    Comment 4b (summarized): The commenter suggests carefully selecting 
medical conditions to ensure a range of therapeutic areas. 
Specifically, they suggest one life-threatening condition (e.g., 
cardiovascular conditions leading to stroke), one chronic condition 
(e.g., atopic dermatitis), and one non-life-threatening and non-chronic 
condition (e.g., urinary tract infection).
    Response 4b: FDA believes this proposed range of medical conditions 
is a great way to choose therapeutic categories. For the current study, 
however, we limited ourselves to medical conditions that have existing 
promotional pieces that include a variety of limitations that can be 
feasibly explained in a disclosure. We will keep the commenter's 
approach in mind and apply it in future research when possible.
    Comment 4c (summarized): The commenter suggests selecting a 
diversity

[[Page 39447]]

of participants, including gender, race, ethnicity, socioeconomic 
status, etc., to better represent the population at large. Also, FDA 
should consider inclusion and exclusion criteria for HCPs and consumers 
carefully.
    Response 4c: We agree that these characteristics are important and 
strive to obtain representativeness across a variety of personal 
demographics. Although we will aim to recruit a diverse group of 
participants with sufficient variation on demographic characteristics 
such as gender, race, age, and education, we note that this study 
features random assignment to condition, whereby these demographic 
characteristics should have an equal chance of occurring. In terms of 
HCPs, we will include them if they are primary care physicians, and 
will work to recruit a sample with sufficient diversity on demographic 
characteristics as noted above.
    Comment 4d (verbatim): It is critical that FDA evaluates the merits 
of unbiased introduction by not presenting a promotional piece to HCPs 
with specialty in the same therapeutic category.
    Response 4d: For this study, we will be recruiting only primary 
care physicians and not specialists. Thus, while any given participant 
may have experience treating one or more of the conditions represented 
by our stimuli, none should have specialties in the respective 
therapeutic categories.
    Comment 4e (summarized): The commenter encourages the use of a 
health literacy competency tool such as a readability calculator to 
ensure consumers can understand the language.
    Response 4e: We agree that the plain language communication of 
information is critical for the best public health outcomes. 
Nevertheless, our aim in this study is to test promotional materials 
that are available in the public domain. Although we have disguised the 
products and campaigns in our mock stimuli, all pieces are derived 
directly from promotion in the marketplace. We feel this is important 
to ensure that our study is relevant.
    Comment 4f (summarized): The commenter recommends recruiting 
through hospitals, doctor offices, and clinics rather than via the 
internet. The commenter suggests that this will expand on the pool of 
participants, help minimize potential bias, and ensure the entire 
population of the United States is represented as not everyone has 
access to or uses the internet.
    Response 4f: Please see our response to comment 2a.
    Comment 4g (summarized): The commenter recommends conducting 
subgroup analyses, such as with older adults.
    Response 4g: We will examine covariates including age, race, and 
education level to determine whether these variables have any effect on 
our findings. This study is not designed to conduct between-subgroup 
analyses. If we detect relevant trends, such subgroup analyses may 
become good candidates for future studies.
    Comment 4h (verbatim): [The commenter] recommends that the FDA 
communicate the actions they will take based on the study results and 
analysis. We also encourage FDA to provide further communication about 
when FDA will publish the study results, how the study results will be 
applied, and how this will impact the work of FDA.
    Response 4h: Please see our response to comment 1a.
    FDA estimates the burden of this collection of information as 
follows:

                                 Table 2--Estimated Annual Reporting Burden \1\
----------------------------------------------------------------------------------------------------------------
                                                   Number of
           Activity                Number of     responses per   Total annual    Average burden     Total hours
                                  respondents     respondent       responses      per response          \2\
----------------------------------------------------------------------------------------------------------------
                                                    Consumers
----------------------------------------------------------------------------------------------------------------
Pretest Screener..............             833               1             833  0.03 (2 minutes)              25
Pretest.......................             500               1             500  0.33 (20                     165
                                                                                 minutes).
Eye-Tracking Screener.........              80               1              80  0.08 (5 minutes)               7
Eye-Tracking Study............              20               1              20  1...............              20
Main Study Screener...........           2,500               1           2,500  0.03 (2 minutes)              75
Main Study....................           1,500               1           1,500  0.33 (20                     495
                                                                                 minutes).
----------------------------------------------------------------------------------------------------------------
                                                      HCPs
----------------------------------------------------------------------------------------------------------------
Pretest Screener..............             735               1             735  0.03 (2 minutes)              22
Pretest.......................             500               1             500  0.33 (20                     165
                                                                                 minutes).
Eye-Tracking Screener.........              80               1              80  0.08 (5 minutes)               7
Eye-Tracking Study............              20               1              20  1...............              20
Main Study Screener...........           2,206               1           2,206  0.03 (2 minutes)              67
Main Study....................           1,500               1           1,500  0.33 (20                     495
                                                                                 minutes).
                               ---------------------------------------------------------------------------------
    Total.....................  ..............  ..............  ..............  ................           1,563
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.
\2\ Rounded to the next full hour.

II. References

    The following references are on display in the Dockets Management 
Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 
1061, Rockville, MD 20852 and are available for viewing by interested 
persons between 9 a.m. and 4 p.m., Monday through Friday; they are also 
available electronically at https://www.regulations.gov. 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. Dodge, T. and A. Kaufman. ``What Makes Consumers Think Dietary 
Supplements Are Safe and Effective? The Role of Disclaimers and FDA 
Approval.'' Health Psychology, 26(4), 513-517. (2007).
2. Dodge, T., D. Litt, and A. Kaufman. ``Influence of the Dietary 
Supplement Health and Education Act on Consumer Beliefs About the 
Safety and Effectiveness of Dietary Supplements.'' Journal of Health 
Communication: International Perspectives. 16(3), 230-244. (2011).

[[Page 39448]]

3. Mason, M.J., D.L. Scammon, and X. Feng. ``The Impact of Warnings, 
Disclaimers and Product Experience on Consumers' Perceptions of 
Dietary Supplements.'' Journal of Consumer Affairs, 41(1), 74-99. 
(2007).
4. France, K.R. and P.F. Bone. ``Policy Makers' Paradigms and 
Evidence from Consumer Interpretations of Dietary Supplement 
Labels.'' Journal of Consumer Affairs, 39(1), 27-51. (2005).
5. FTC. ``Full Disclosure.'' Accessed at: https://www.ftc.gov/news-events/blogs/business-blog/2014/09/full-disclosure (September 23, 
2014) Last accessed on June 22, 2018.
6. Higgins, E., M. Leinenger, and K. Rayner. ``Eye Movements When 
Viewing Advertisements.'' Frontiers in Psychology, 5, 210. (2014).
7. Pieters, R., M. Wedel, and R. Batra. ``The Stopping Power of 
Advertising: Measures and Effects of Visual Complexity.'' Journal of 
Marketing, 74(5), 48-60. (2010).
8. Thomsen, S. and K. Fulton. ``Adolescents' Attention to 
Responsibility Messages in Magazine Alcohol Advertisements: An Eye-
Tracking Approach.'' Journal of Adolescent Health, 41, 27-34. 
(2007).
9. Simola, J., J. Kuisma, A. [Ouml][ouml]rni, L. Uusitalo, et al. 
``The Impact of Salient Advertisements on Reading and Attention on 
Web pages.'' Journal of Experimental Psychology: Applied, 17(2), 
174-190. (2011).
10. Wedel, M. and R. Pieters. ``A Review of Eye-Tracking Research in 
Marketing.'' In Review of Marketing Research, vol. 4 (pp. 123-147), 
N. K. Malhotra (Ed.). Armonk, New York: M. E. Sharpe. (2008).

    Dated: August 3, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-17045 Filed 8-8-18; 8:45 am]
 BILLING CODE 4164-01-P


