Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment Request; Utilization of Adequate Provision Among Low to Non-Internet Users, 10855-10862 [2018-04996]

Agencies

• Food and Drug Administration
• DEPARTMENT OF HEALTH AND HUMAN SERVICES

[Federal Register Volume 83, Number 49 (Tuesday, March 13, 2018)]
[Notices]
[Pages 10855-10862]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-04996]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2017-N-0493]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Utilization of 
Adequate Provision Among Low to Non-Internet Users

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 either electronic or written comments on the collection 
of information by April 12, 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 ``Utilization of Adequate Provision Among Low to Non-internet 
Users.'' 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: 

I. Background

    In compliance with 44 U.S.C. 3507, FDA has submitted the following 
proposed collection of information to OMB for review and clearance.

Utilization of Adequate Provision Among Low to Non-Internet Users

OMB Control Number 0910-NEW

    Section 1701(a)(4) of the Public Health Service Act (42 U.S.C. 
300u(a)(4)) authorizes FDA to conduct research relating to health 
information. Section 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.
    Prescription drug advertising regulations require that broadcast 
advertisements containing product claims present the product's major 
side effects and contraindications in either audio or audio and visual 
parts of the advertisement (21 CFR 202.1(e)(1)); this is often called 
the major statement. The regulations also require that broadcast 
advertisements contain a brief summary of all necessary information 
related to side effects and contraindications or that ``adequate 
provision'' be made for dissemination of the approved package labeling 
in connection with the broadcast (Sec.  202.1(e)(1)). The requirement 
for adequate provision is generally fulfilled when a firm gives 
consumers the option of obtaining FDA-required labeling or other 
information via a toll-free telephone number, through print 
advertisements or product brochures, through information disseminated 
at health care provider offices or pharmacies, and through the internet 
(Ref. 1). The purpose of including all four elements is to ensure that 
most of a potentially diverse audience can access the information.
    Internet accessibility is increasing, but many members of certain 
demographic groups (e.g., older adults, low socioeconomic status 
individuals) nonetheless report that the internet is inaccessible to 
them either as a resource or due to limited knowledge, and so a website 
alone may not adequately serve all potential audiences (Refs. 2 and 3). 
Similarly, some consumers may prefer to consult sources other than a 
health care provider to conduct initial research, for privacy reasons 
or otherwise (Refs. 1, 4, and 5). In light of these considerations, the 
toll-free number and print ad may provide special value to consumers 
who are low to non-internet users and/or those who value privacy when 
conducting initial research on a medication, though not necessarily 
unique value relative to one another. As such, a primary purpose of 
this research is to examine the value of including both the toll-free 
number and print ad as part of adequate provision in direct-to-consumer 
(DTC) prescription drug broadcast ads. We will also investigate the 
ability and willingness of low to non-internet users to make use of 
internet resources if other options were unavailable. These questions 
will be assessed using a survey methodology administered via telephone.
    In addition, building on concurrent FDA research regarding drug 
risk

[[Page 10856]]

information,\1\ we will assess risk perceptions as influenced by 
opening statements that could be used to introduce risks in DTC 
prescription drug broadcast ads. Opening statements may be used to 
frame risk information that follows. As such, consumers may interpret 
the likelihood, magnitude, and duration of risks differently depending 
on how those risks are introduced (Refs. 6-9). The intended outcome of 
this component of the research is to evaluate the influence of these 
opening statements within a sample of low to non-internet users. This 
research question will be addressed using a 1 x 3 between-subjects 
experimental design embedded in the previously mentioned survey. This 
particular component of the research will serve as an exploratory test 
intended to inform FDA's future research efforts.
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    \1\ https://www.federalregister.gov/documents/2015/01/13/2015-00269/agency-information-collection-activities-submission-for-office-of-management-and-budget-review.
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    Sampling Frame. Given that older adults (i.e., those aged 65 and 
older) are among the largest consumers of prescription drugs (Ref. 10) 
and that approximately 41 percent of older adults do not use the 
internet (Ref. 2), investigating use of adequate provision in this 
population is especially important. Also of concern, 34 percent of 
those with less than a high school education do not use the internet, 
23 percent of individuals with household incomes lower than $30,000 per 
year do not use the internet, and 22 percent of individuals living in 
rural areas do not use the internet (Ref. 2). These estimates capture 
non-internet users, and so consideration of low-internet users warrants 
additional concern. Consistent with these citations, the present 
research will utilize a nationally representative sample of low to non-
internet users from these and other relevant demographic groups.
    Data collection will utilize a random digit dialing (RDD) sample 
that has been pre-identified as being a non-internet household, or 
having at least one non-internet using member. This sample solution is 
ideal because it relies on a dual-frame (landline and cell phone) 
probability sample, yet has the advantage of prior knowledge of those 
who are likely to be low to non-internet users (re-screening will 
verify this). The Social Science Research Solutions (SSRS) Omnibus, 
within which this survey will be embedded, utilizes a sample designed 
to represent the entire adult U.S. population, including Hawaii and 
Alaska, and including bilingual (Spanish-speaking) respondents. As 
reflected in the overall population of low to non-internet users, we 
intend to collect a small sample of Spanish-speaking individuals, which 
comprise a subsample of the regular landline and cell phone RDD 
sampling frames. We will also screen for past and present prescription 
drug use in order to ensure a motivated sample.
    Survey Protocol. This survey will be conducted by telephone on 
landline and cell phones, with an expected 50 to 60 percent of 
interviews conducted on cell phones. Interviewing for the pretest and 
main study will be conducted via SSRS's computer-assisted telephone 
interviewing system. We expect to achieve a roughly 40 percent survey 
completion rate from the pre-identified respondents to be sampled in 
this study, given an 8-week field period and a maximum of 10 attempts 
to reach respondents. The original SSRS Omnibus from which this sample 
is derived receives an approximately 8 to 12 percent response rate. 
These are not uncommon response rates for high-quality surveys and have 
been found to yield accurate estimates (Refs. 11 and 12).
    As communicated earlier, the primary focus of interview questions 
concern the ability and willingness of low to non-internet users to 
utilize the various components of adequate provision, particularly the 
toll-free number and print ad components. In addition to these 
questions, experimental manipulations will be embedded in the survey as 
an exploratory test to assess the impact of opening statements that 
could be used to introduce risks in DTC prescription drug broadcast 
ads, which is a related concept. To form the experimental 
manipulations, participants will be presented with a statement of major 
risks and side effects (``the major statement'') drawn from a real 
prescription drug product, but modified to include only serious and 
actionable risks. Preceding this description of major risks will be one 
of three opening statements: (1) ``[Drug] can cause severe, life 
threatening reactions. These include . . .''; (2) ``[Drug] can cause 
serious reactions. These include . . .''; or (3) ``[Drug] can cause 
reactions. These include . . .'' All risk statements will conclude with 
the following language: ``This is not a full list of risks and side 
effects. Talk to your doctor and read the patient labeling for more 
information.'' Participants will be randomly assigned to experimental 
condition, and all manipulations will be pre-recorded to allow for 
consistent administration. Following exposure to these manipulations, 
participants will respond to several questions designed to assess risk 
perceptions.
    Before the main study, we will execute a pretest with a sample of 
25 participants from the same sampling frame as outlined. The pretest 
questionnaire will take approximately 15 minutes to complete. The goal 
of the pretest will be to assess the questionnaire's format and the 
general protocol to ensure that the main study is ready for execution. 
To test the protocol among the target groups, we will seek to recruit a 
mix of participants based on demographic and other characteristics of 
interest. We do not plan to use incentives for the pretest or main 
study portions of this survey. However, upon request, cell phone 
respondents may be offered $5 to cover the cost of their cell phone 
minutes.
    Questionnaire development is an iterative process and so the main 
study questionnaire will include any changes from pretesting, as well 
as other outcomes, such as OMB and public comments. Like pretesting, 
the main study questionnaire should take approximately 15 minutes to 
complete. Based on a power analyses, the main study sample will include 
approximately 1,996 participants. This sample size will allow us to 
draw statistical comparisons between the various demographic groups in 
the sample.
    Measurement and Planned Analyses. Consistent with the larger 
purpose of the study, survey questions will examine access, technical 
ability, and willingness to use adequate provision options; preference 
for and experience using adequate provision options; privacy concerns; 
and potentially other secondary questions of interest. In addition, to 
assess the impact of the experimental manipulations, survey questions 
will assess perceived risk likelihood, perceived risk magnitude, and 
perceived risk duration. Demographic information will also be 
collected. To examine differences between experimental conditions, we 
will conduct inferential statistical tests such as analysis of 
variance. A copy of the draft questionnaire is available upon request.
    In the Federal Register of June 12, 2017 (82 FR 26934), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. Comments received along with our responses 
to the comments are provided 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

[[Page 10857]]

not fully captured by our paraphrasing. The following acronyms are used 
here: FRN = Federal Register Notice; DTC = direct-to-consumer; FDA and 
``The Agency'' = Food and Drug Administration; OPDP = FDA's Office of 
Prescription Drug Promotion.
    Comment 1a, regulations.gov tracking number 1k1-8y16-3nqx 
(summarized): The commenter expresses support for FDA's collective 
research and welcomes the Agency's current proposed survey examining 
adequate provision.
    Response to Comment 1a: We appreciate and thank the commenter for 
their support.
    Comment 1b (verbatim): Throughout the main survey questionnaire, 
some questions ask about ability to obtain information on prescription 
drugs after seeing an advertisement on television. These questions 
presume access to a television. If understanding this process of first 
seeing an ad on TV then searching for information is the key objective, 
we suggest in the screening criteria ensuring all respondents have 
access to a TV and/or watch television on a regular basis.
    Response to Comment 1b: We have added a screening question to 
confirm that participants watch television at least occasionally.
    Comment 1c (verbatim): As currently outlined, the sample frame is 
relatively broad in that it includes those who possibly do not have 
experience with prescription medications or experience searching for 
prescription medication information. Respondents without experience in 
this area could provide speculative responses to many questions, and 
thus, [the commenter] suggests that they are outside of the scope. To 
address this, we recommend adding a screening question or questions to 
include only those who have had at least one medical condition which 
has required prescription medication within the last 12 months.
    Response to Comment 1c: To ensure a motivated sample, we included a 
question to screen for past or present prescription drug use.
    Comment 1d (verbatim): The purpose of the secondary objective of 
the study pertaining to risk statements is not entirely clear. Since 
the sample frame is not restricted to those who suffer from a condition 
which could be helped by the mock drug, responses have the possibility 
to be speculative and reflect bias of people coming in to the study 
rather than what is intended. For instance, respondents who happen to 
be within a population targeted by the major statements are reasonably 
more likely to report a higher likelihood of experiencing a stated side 
effect and reporting a higher seriousness of them, biasing experiment 
responses.
    Response to Comment 1d: The secondary objective of the study is 
designed to assess the impact of opening statements that could be used 
to introduce risks in DTC prescription drug broadcast ads. This 
objective complements previously published research and adds value by 
newly investigating the impact of framing statements among a sample of 
low to non-internet users. Our approach involves random assignment to 
experimental conditions which should lead to approximately equal 
numbers of diagnosed versus undiagnosed individuals in each of the 
conditions, lessening any concern about bias. Nonetheless, please 
understand that this secondary objective is intended to provide a 
preliminary assessment of the stated research questions for development 
purposes. Procedurally, this objective will involve only a brief 
presentation of a short audio broadcast followed by three questions, 
allowing us to gather this valuable information with very low burden to 
participants who are already engaged in our larger survey regarding 
adequate provision.
    Comment 1e (verbatim): Additionally, information gained from the 
experimental manipulations (E-1 through E-3) will only be applicable to 
hearing the opening and major statement presented over the phone, 
rather than versus being read through print or online. Interpretations 
and understanding of this info could differ between the media. While 
this could possibly be a useful supplement to current knowledge, the 
learnings will likely not be directly applicable to the other media. If 
comparison of interpretation between the media is the goal of this 
section, [the commenter] suggests a stand-alone study would better 
address that goal rather than an addendum to this one.
    Response to Comment 1e: We appreciate this limitation of our 
preliminary assessment and intend to take it into consideration when 
interpreting results.
    Comment 1f (verbatim): Screener: The current screener terminates 
cell phone users who have not browsed the internet in the past month (S 
I). It is not readily apparent why this group should not participate in 
the survey. We would suggest that the termination criteria be removed 
from this question as it may make incremental improvement to response 
rates.
    Response to Comment 1f: The screener only excludes cell phone users 
(T1 = 2) who choose ``don't know'' (- 98) or refuse the question (- 99) 
(S1 < 0).
    Comment 1g (verbatim): As is, it is unclear what an independent 
variable for the questionnaire is intended to be. One possibility [the 
commenter] suggests is including a question aimed at understanding the 
overall preference for source of information, which would serve as the 
independent variable in the study or could be combined with the ability 
and access questions to make a composite variable. (e.g., ``What is 
your preferred medium in which to receive prescription drug 
information: Print ads for the drug; the manufacturer's phone number or 
website; or asking your healthcare provider?'')
    Response to Comment 1g: Please refer to the instruction set 
preceding question 3. Our questionnaire attempts to learn about patient 
preferences through questions about participant likelihood to seek 
information via the various available sources, as well as past use, 
ability, and willingness, among other constructs. We believe these 
constructs to provide adequate assessment of consumer preference to 
obtain additional information via the various available sources. 
Moreover, we note that another commenter (see Comment 3n) takes the 
position that we should not inquire about patient preferences. We have 
considered both of the perspectives when deciding upon potential 
revisions.
    Comment 1h (verbatim): Throughout the survey, [the commenter] 
suggests defining each point on the 5 point scales used to avoid 
confusion by respondents. In our consumer research efforts, we 
customarily use 5 point scales that are defined at each point, such as 
`Excellent, Very Good, Good, Poor, and Very Poor'.
    Response to Comment 1h: We concur that defining each point on 5 
point scales helps mitigate confusion and have revised the 
questionnaire to define each point of scales.
    Comment 1i (verbatim): It seems inappropriate to use a Likert scale 
to answer ``Q1: Access to sources of information'', as it would seem 
access could be defined more narrowly--No access, some access, or 
complete access. We suggest using the pre-test to examine this question 
in particular to ensure either that the current scale is interpreted 
correctly or determine an appropriate re-wording. Additionally, it 
could be helpful to include the more specific options as distinct 
answer choices (e.g. an option for internet at a public library and a 
separate option for internet at a coffee shop) in order to provide more 
granular information which could be useful to the FDA as

[[Page 10858]]

well as industry as a whole. We suggest using the pre-test to produce a 
full list of options as well as any appropriate re-wordings.
    Response to Comment 1i: We agree that defining access more narrowly 
may be sufficient for this question and so we have adopted this 
approach in our revised survey. We will also evaluate responses to this 
narrowed scale in our analysis of pretest data. We also appreciate the 
value of assessing locations of access; however, we consider such 
questions to be of lesser relevance to our key objectives, and we have 
sought to limit the duration of the survey to less than 15 minutes. 
Consequently, we do not adopt this recommendation.
    Comment 1j (verbatim): Throughout the survey, we suggest adding in 
``Talked with your doctor'' as an answer choice among the options for 
sources of information. Physicians are a major source of product 
information and ``talking with a doctor'' are what drug advertisements 
generally suggest to consumers, so inclusion of this option is 
appropriate.
    Response to Comment 1j: We agree that health care providers are one 
important source for adequate provision. Nonetheless, the current 
investigation is designed to assess the utility of the various options 
for disseminating additional product risk information, and speaking 
with a health care provider is not under reevaluation. Consequently, we 
ask participants to respond under the premise that they are seeking 
information prior to approaching a health care professional.
    Comment 1k (verbatim): As currently worded, question 13 has the 
possibility to lead the respondent by stating that ``Some people change 
their approach . . .'' The current wording could bias respondents to be 
overly critical. [The commenter] would suggest either changing the 
question or adding in a new question prior to the current Q 13 to 
ascertain a rating of the level of privacy offered by each information 
source. This new question would provide the respondents current 
perceptions of privacy, something which the survey omits. For example, 
a newly worded question could be as follows: ``On a 5-point scale, in 
which 1 is Very Low Privacy and 5 is Very High Privacy, what is the 
level of privacy offered by each of the following information sources 
when getting full prescription-drug product information?'' The current 
question 13 could then follow this question.
    Response to Comment 1k: Our intention with this question (and its 
wording) is to facilitate comparisons between baseline likelihood to 
use the various sources of adequate provision (see Q3) and likelihood 
to use the various options in cases where privacy is a concern. By 
stating ``Some people change their approach . . . '' we hoped to give 
participants permission to respond differently than they had in the 
earlier question, if they felt a change in their response was 
appropriate. Nonetheless, we recognize that this language could be 
leading and so we have eliminated it from our revised questionnaire. We 
are hopeful that the revised question will still allow us to draw the 
intended comparisons.
    Comment 1l (verbatim): In addition to our concerns regarding the 
goal of the experiment questions (E 1-E2), the purpose in the 
variations of the major statements is unclear. The objectives state 
that varying opening statements (E I) are the secondary focus of this 
research, not major statements. We suggest choosing an appropriate 
major statement in the pre-tests and then using that in the broader 
fielding of the study.
    Response to Comment 1l: The purpose of varying the major statements 
was to add to the generalizability of our findings. The revised version 
of our survey adopts this commenter's recommendation and includes only 
one version of the major statement.
    Comment 1m (verbatim): We suggest adding a ``Don't know'' option 
for EI-E3 as respondents might not be able to assess how long lasting, 
serious, or likely the side effects would be. The current range of 
answer choices may force inaccurate or speculative responses; a ``Don't 
Know'' answer would be a legitimate choice and informative for the 
study. Our standard practice is to provide a ``Don't Know'' option 
whenever it could be a valid answer.
    Response to Comment 1m: The items used in this section were 
developed through scale validation research and thus we prefer to 
retain them in their original form. Nonetheless, we have added labels 
to each point on the scales in response to Comment 1h, and the midpoint 
(``neutral'') of these scales may be treated similarly to a ``Don't 
Know'' option.
    Comment 2a, regulations.gov tracking number 1k1-8xz6-t7bj 
(verbatim): The practical utility of this study is unclear. Currently, 
industry is broadly executing on making labeling available via both IN 
[internet] and non-IN based options to a diverse audience. 
Historically, there were many options available to enable patients to 
locate drug-related labeling, even before the IN became available. When 
added to the three options mentioned above, the IN provides patients 
with a fourth option, one that is increasingly at a patient's fingertip 
via tablet, cell phone, or laptop. Hence, it is unclear how results 
from this study will enhance consumer access to information or be 
applied to modify current practices.
    Response to Comment 2a: As stated in the 60-day FRN (82 FR 26934), 
our intention is to assess the utility of the various sources of 
adequate provision among a sample of low to non-internet users. For 
example, it may not be necessary to include both a print ad reference 
and toll free number reference. We have received inquiries along these 
lines from stakeholders. Additionally, we may find that low to non-
internet users would be willing to use the internet themselves or with 
the help of a friend or family member if non-internet options were 
unavailable. This research will provide insights to inform our approach 
to the adequate provision requirement.
    Comment 2b (verbatim): The sampling frame focuses on those ``not 
likely to have IN access'' as defined by FDA and includes older adults, 
with less than a high school education, who make less than $30,000/
year, and live in rural areas; it also includes bilingual Spanish 
speakers. Yet it is not clear how persons not likely to have IN access 
would be able to inform FDA about how they would behave if they had 
access to the IN and other options were not available. Rather than 
speculate about how their behavior might change if faced with IN access 
and no other options, it would be better to design a study that focuses 
on understanding the effectiveness of non-IN options to provide 
information in general.
    Response to Comment 2b: To be clear, we intend to sample from the 
above referenced populations separately, as opposed to sampling from 
one population with all these attributes.
    As indicated in the 60-day FRN (82 FR 26934), we do intend to 
assess the effectiveness of non-internet options. However, as a 
secondary objective, it seems to us worthwhile to also consider how low 
to non-internet users may respond if non-internet options were 
unavailable. As another commenter indicates (see Comment 3b), internet 
use is widespread and technological sources of adequate provision may 
suffice (when combined with recommendation to speak to a health care 
professional). We hope to shed light on this question through our 
research.
    Comment 2c (verbatim): Questions 1-5 and 13: The current choices do 
not assess the respondent's willingness or ability to visit their 
healthcare provider

[[Page 10859]]

to obtain the approved package labeling. This option should be added.
    Response to Comment 2c: Please refer to Comment 1j and our 
associated response.
    Comment 2d (verbatim): Question 15: Given the length of the package 
labeling making it impractical to receive the information verbally, it 
would be likely that callers would prefer an option, Mail the 
prescription drug product information to me, even when faced with 
privacy concerns.
    Response to Comment 2d: This response option has been added to our 
revised questionnaire.
    Comment 2e (verbatim): Instructions for Experimental Manipulations, 
E1/E2: E2 includes three different versions of the major statements. If 
the intended outcome of this component of the research is to evaluate 
the influence of these opening statements within a sample of low to 
non-IN users, and risk perceptions will be assessed as influenced by 
opening statements that could be used to introduce risks, it is unclear 
why the major statements (E2: A, B, C) differ when assessing whether or 
not opening statements (E1: 1, 2, 3) influence risk perceptions.
    Response to Comment 2e: Please refer to Comment 1l and our 
associated response.
    Comment 3a, regulations.gov tracking number 1k1-8y13-m7td: 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 five years and 
articulate a clear vision for its research priorities for the near 
future.''
    Response to Comment 3a: 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 
health care providers can make informed decisions about treatment 
options. OPDP's research program supports this mission by providing 
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 FRNs and peer-reviewed publications 
produced by our office. The website maintains information on all 
studies we have conducted, dating back to a DTC survey conducted in 
1999.
    Comment 3b; the commenter provided a summary of their comments 
followed by a more detailed description of the same comments. For 
brevity, only the summary of comments (verbatim) is provided below. 
Full comments may be accessed at regulations.gov via tracking number 
1k1-8y13-m7td.
    First, FDA's proposed research appears to offer limited practical 
utility in several ways:
     The Agency proposes research based on an outdated, 18-
year-old guidance document that fails to recognize adequately the 
societal and technological changes of the last two decades, including 
the many options now available to satisfy the adequate provision 
requirement.
     FDA regulations require adequate, not complete, provision. 
Given the prevalence of the internet and smartphones across all U.S. 
demographic groups, we believe that biopharmaceutical manufacturers can 
satisfy adequate provision simply through information dissemination at 
health care provider offices or pharmacies, a 1-800 number, and/or the 
internet.
     FDA fails to recognize existing research that demonstrates 
the pervasiveness of the internet and smartphones in the United States. 
This research limits any potential utility of the proposed study. The 
Agency's proposal mainly relies on data from six to 16 years ago. The 
smartphone is dramatically increasing internet connectivity for 
traditionally low to non-internet use demographic groups. Further, FDA 
does not acknowledge that older adults (with or without internet 
access) tend to rely on others, including family and health care 
personnel, for drug information.
    Response to Comment 3b: FDA recognizes that a large proportion of 
the U.S. population utilizes the internet. It is specifically for this 
reason that we are conducting research to inform our current guidance 
recommendations. Nonetheless, as indicated in the 60-day FRN (82 FR 
26934), certain segments of the U.S. population are unlikely to use the 
internet. For example, 41 percent of individuals aged 65 and older do 
not use the internet, yet are the largest consumers of prescription 
drugs. As the commenter states, some individuals from this demographic 
rely on others to obtain drug information, but this perspective does 
not take into account the desire for privacy in obtaining such 
information, or the availability of these other individuals. The 
proposed research will provide empirical assessment of how vulnerable 
populations such as older adults may be impacted by changes to 
regulatory policy.
    The assertion that the requirement for ``adequate'' provision can 
be fulfilled by disseminating information through ``health care 
provider offices or pharmacies, a 1-800 number, and/or the internet'' 
may be correct, and FDA invites the commenter to submit data supportive 
of this perspective. FDA maintains a science-based approach to its 
regulatory decisionmaking, and as such, the current research is 
designed to inform our thinking in this area.
    We disagree with the assertion that our proposal relied mainly on 
data from 6 to 16 years ago. A more careful review of the FRN will show 
that our key citations range from 2013 to the present. By necessity, we 
also cite the relevant 1999 guidance, as well as a few other references 
which speak to general patterns of human behavior.
    Comment 3c (summarized): The commenter recommends removal of the 
second proposed study concerning opening statements to frame risk 
information on the grounds that (a) questions regarding adequate 
provision may impact responding in the second

[[Page 10860]]

proposed study and (b) a low to non-internet user sample is not 
sufficiently diverse.
    Response to Comment 3c: Please refer to Comment 1d and our 
associated response.
    Comment 3d (summarized): The commenter provides several 
recommendations pertaining to subject enrollment. The first comment on 
this topic ``recommends that FDA ensure that the subject sample 
includes representative portions of alleged subpopulations of low to 
non-internet users, including older adults, low socioeconomic status 
individuals, people with less than a high school education, and 
individuals living in rural areas.''
    Response to Comment 3d: To obtain a nationally representative 
sample of the target population of adult low to non-internet users who 
are also prescription drug users, the research team will use a sample 
sourced from a dual frame. This approach involves using a random digit 
dialing sample that has been pre-identified as being a non-internet 
household (or having at least one non-internet using member). The 
demographics within this frame of low to non-internet users fall within 
the expected range of subpopulations with respect to older adults, low 
socioeconomic status, and people with less than a high school education 
or some college. The sample is designed to represent the adult U.S. 
population (including Hawaii and Alaska) and will include rural areas. 
This sample solution is ideal because it relies on a dual-frame 
probability-sample, yet has the advantage of already knowing who are 
likely to be low to non-internet users.
    Comment 3e (summarized): In the second comment pertaining to 
subject enrollment, the commenter recommends that participants reached 
via smartphone not be included in the sample.
    Response to Comment 3e: We agree that smartphone use is increasing 
internet access for traditionally low to non-internet use demographics 
and appreciate the importance of confirming our sample are low to non-
internet users. Notwithstanding, we are screening based on self-
reported internet browsing, such that individuals who report browsing 
the internet three or more times in the past month--regardless of 
medium--will not be asked to participate in the survey. Further, the 
current approach supports that only households which have been pre-
identified as having at least one non-internet using member will be 
screened for participation, adding an additional layer of assurance 
that only low to non-internet users will be asked to participate in the 
questionnaire.
    Comment 3f (summarized): In the third comment pertaining to subject 
enrollment, the commenter recommends collecting data in-person because 
data collection via phone may impact responses regarding the 1-800 
number.
    Response to Comment 3f: We acknowledge that in-person data 
collection would add value to the proposed research but cost 
implications bar us from pursuing it. We will consider implications of 
our protocol for survey administration when interpreting results.
    Comment 3g (summarized): In the final comment pertaining to subject 
enrollment, the commenter indicates agreement with the proposed 
approach to screen for past and present prescription drug use in order 
to ensure a motivated sample.
    Response to Comment 3g: We appreciate the support for this planned 
approach.
    Comment 3h: Remaining comments pertain to the draft study 
questionnaire. The first comment on this topic suggests that certain 
items may lead participants to respond in certain ways. Examples 
(abbreviated for brevity) include:
     The instructions for Q3 of the Main Study Survey state: 
``Prescription drugs advertised on television provide only limited 
product information. For example, not all of the product's risks and 
side effects are described. Imagine you wanted to obtain additional 
product information before seeing your health care provider.'' As 
previously mentioned, while research ``reveal[s] consumers engage in 
some prescription drug information seeking . . . most takes place after 
visiting a doctor, not before'' (emphasis added [by commenter]). The 
question prompt does not reflect common practice and may lead to a 
misleading answer. Both the prompt and question itself should be 
revised to reflect that subjects may look specifically to their 
healthcare provider for this information.
     Further, the Main Study Survey introduces questions about 
privacy by stating: ``Next, I will ask about privacy concerns you might 
have when getting full prescription-drug product information.'' Such 
phrasing suggests that a subject should have ``concerns'' in this 
context. Q12 asks subjects to ``rate the extent to which you value 
privacy . . . '' (emphasis added [by commenter]). Such language 
suggests subjects should indeed ``value'' privacy.
     The prompt for Q13 is also leading by introducing the 
question with: ``Some people change their approach to getting 
information about prescription drugs when privacy is a concern.''
    Response to Comment 3h: As the commenter indicates in the first 
comment, there is evidence to suggest that consumers seek information 
both before and after visiting with a health care professional. 
Moreover, the ubiquity of DTC prescription drug advertising suggests 
that pharmaceutical companies are well aware of the advantages of 
introducing products to consumers prior to the consumer-health care 
provider interaction. The proposed research is concerned with how low 
to non-internet users access full product information prior to 
approaching a health care professional. As such, we need to provide 
this context to participants before they can respond regarding their 
interest and experiences within this context. We disagree that our 
presentation here is leading as the commenter describes, and 
consequently, we retain our current approach with these questions.
    Likewise, in response to the second comment, we cannot inquire 
about privacy concerns without referencing privacy concerns. 
Nonetheless, we have revised Q12 to read ``How much value do you place 
on privacy . . .''
    In response to the third comment, please see Comment 1k and our 
associated response.
    Comment 3i (summarized): The second comment pertaining to the study 
questionnaire concerned definitions and terms. The commenter states, 
``The questionnaires do not define certain key terms (e.g., side 
effect, risk, serious, reference, full product information, partial 
information). Subjects may interpret these terms based on different 
standards. For example, for Q16 of the Main Study Survey, FDA may wish 
to provide context for what could constitute ``complete prescription-
drug product information. FDA should consider providing user-friendly 
definitions or terms throughout the questionnaires.''
    Response to Comment 3i: We appreciate the importance of ensuring 
uniform interpretation of terms. In cognitive interviews preceding this 
work, we assessed whether individuals interpret key terms similarly and 
made revisions where necessary. We have also considered the additional 
time (burden) that would be required to complete the survey if every 
term were defined in the pretest and main study. We have targeted to 
keep the current information collection to under 15 minutes per 
respondent. With these factors in mind, we have chosen not to provide 
additional definitions.

[[Page 10861]]

    Comment 3j (summarized): The third comment pertaining to the study 
questionnaire concerned the sliding scale format of certain questions: 
``FDA should consider replacing the sliding scale format (especially 
for Q1-Q3 of the Main Study Survey) with a binary or ``Yes-No-Neutral'' 
scheme. The sliding-scale format is at times confusing in form, 
inappropriately frames certain questions, and could potentially 
introduce error.''
    Response to Comment 3j: Please see Comment 1i and our associated 
response.
    Comment 3k: The final comments pertaining to the questionnaire were 
characterized by the commenter as miscellany. The first comment read, 
``As previously mentioned in Section II.A, E1-E3 of the Main Study 
Survey should be eliminated. (reference omitted) Similarly, we would 
also recommend that elimination of ``Other Questions of Interest'' 
(Q16-Q20) of the Main Study Survey, which appear to have limited 
applicability to the study of adequate provision.''
    Response to Comment 3k: In regards to E1-E3, please see Comment 1d 
and our associated response. In regards to Q16-Q20, all these items 
provide potentially valuable information relevant to the topic of 
interest, and therefore we prefer to retain them.
    Comment 3l: The next comment characterized as miscellany read: 
``The Study Screener introduction should not state that the survey is 
being conducted ``on behalf of the Food and Drug Administration'' and 
that study results ``will be used in the consideration of important 
policy decisions.'' These statements could potentially influence 
subjects' responses to study questions. Instead, this information might 
be provided at the conclusion of the study.''
    Response to Comment 3l: Such statements are intended to communicate 
the legitimacy of the study to potential participants, and thus 
validate participation. Upon further consideration, we concur that 
these statements may potentially influence responses, and we have 
removed them.
    Comment 3m: The next comment characterized as miscellany read: 
``The Main Study Survey should include a similar question to Q5, 
inquiring about if a toll-free number was not available.''
    Response to Comment 3m: We acknowledge the potential value of this 
question, but given the key objectives of the research, and concerns 
about participant burden, we decline to adopt this recommendation. We 
have targeted to keep the current information collection to under 15 
minutes per respondent.
    Comment 3n: Continuing under the miscellany category: ``There are 
several questions of the Main Study Survey (e.g., questions associated 
with Instructions_2) that inquire about a subject's preferences 
regarding the provision of product labeling. We do not understand the 
utility of these questions. Again, FDA's regulation concerns adequate, 
not preferred, provision.''
    Response to Comment 3n: In deciding upon potential revisions, we 
have considered both this commenter's views and those of another 
commenter (see Comment 1g) which recommend utilizing consumer 
preferences as an independent variable. We agree with the first 
commenter that consumer preferences are crucial for understanding the 
issues at hand as articulated in the 60-day FRN (82 FR 26934). 
Consequently, we have retained these questions.
    Comment 3o: The next miscellany comment read: ``Certain questions, 
like Q4 and Q5 of the Main Study Survey, should include the option of 
asking a health care provider. Such a choice is part of FDA's adequate 
provision recommendation in the Guidance Document.''
    Response to Comment 3o: Please see Comment 1j and our associated 
response.
    Comment 3p: The next miscellany comment read: ``The ordering of the 
questions (web page, toll-free number, print ad) of the Main Study 
Survey could potentially introduce bias. FDA may want to randomize the 
ordering of questions (e.g., Q6-Q11) to eliminate such bias.''
    Response to Comment 3p: We accept this recommendation and will 
randomize the ordering of questions Q6 to Q11 pertaining to web page, 
toll-free number, and print ad.
    Comment 3q: The final comment characterized as miscellany read: 
``Q15 of the Main Study Survey should include an option of mailing 
information to the customer.''
    Response to Comment 3q: Please see Comment 2d and our associated 
response.
    FDA estimates the burden of this collection of information as 
follows:

                                                         Table 1--Estimated Reporting Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                   Number of
                   Activity                        Number of     responses per   Total annual         Average  burden per  response         Total hours
                                                  respondents     respondent       responses
--------------------------------------------------------------------------------------------------------------------------------------------------------
Pretest Screener..............................              63               1              63  .05 (3 minutes).........................            3.15
Pretest Survey................................              25               1              25  .25 (15 minutes)........................            6.25
Main Study Screener...........................           4,990               1           4,990  .05 (3 minutes).........................           249.5
Main Study Survey.............................           1,996               1           1,996  .25 (15 minutes)........................             499
                                               ---------------------------------------------------------------------------------------------------------
    Total Hours...............................  ..............  ..............  ..............  ........................................           757.9
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

II. References

    The following references are on display in 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; 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. U.S. Department of Health and Human Services, Food and Drug 
Administration (1999). ``Guidance for Industry: Consumer-Directed 
Broadcast Advertisements.'' Available at https://www.fda.gov/RegulatoryInformation/Guidances/ucm125039.htm.
2. Anderson, M. and A. Perrin (2016). ``13% of Americans Don't Use 
the internet: Who Are They?'' Pew Research Center. Available at 
https://www.pewresearch.org/fact-tank/2016/09/07/some-americans-dont-use-the-internet-who-are-they/.
3. U.S. Department of Commerce, U.S. Census Bureau (2013). 
``Computer and internet Use in the United States: Population 
Characteristics.'' Available at https://www.census.gov/prod/2013pubs/p20-569.pdf.

[[Page 10862]]

4. Fox, S. and L. Rainie (2002). ``Vital Decisions: How internet 
Users Decide What Information to Trust When They or Their Loved Ones 
Are Sick. Pew internet & American Life Project.'' Available at 
https://www.pewinternet.org/2002/05/22/main-report-the-search-for-online-medical-help/.
5. DeLorme, D.E., J. Huh, and L.N. Reid (2011). ``Source Selection 
in Prescription Drug Information Seeking and Influencing Factors: 
Applying the Comprehensive Model of Information Seeking in an 
American Context.'' Journal of Health Communication, 16: pp. 766-
787.
6. O'Donoghue, A.C., H.W. Sullivan, K.J. Aikin, et al. (2014). 
``Important Safety Information or Important Risk Information? A 
Question of Framing in Prescription Drug Advertisements.'' 
Therapeutic Innovation and Regulatory Science, 48: pp. 305-307. doi: 
10.1177/2168479013510306
7. Kahneman, D. (2011). Thinking, Fast and Slow. New York, NY: 
Farrar, Straus, and Giroux.
8. Rothman, A.J. and P. Salovey (1997). ``Shaping Perceptions To 
Motivate Healthy Behavior: The Role of Message Framing.'' 
Psychological Bulletin, 121: pp. 3-19.
9. Armstrong, K., J.S. Schwartz, G. Fitzgerald, et al. (2002). 
``Effect of Framing as Gain Versus Loss on Understanding and 
Hypothetical Treatment Choices: Survival and Mortality Curves.'' 
Medical Decision Making, 22: pp. 76-83.
10. National Center for Health Statistics (2016). ``Health, United 
States, 2015: With Special Feature on Racial and Ethnic Health 
Disparities.'' Hyattsville, MD.
11. Brick, J.M. and D. Williams (2013). ``Explaining Rising 
Nonresponse Rates in Cross-Sectional Surveys.'' The Annals of the 
American Academy of Political and Social Science, 645: pp. 36-59.
12. Groves, R.M. (2006). ``Nonresponse Rates and Nonresponse Bias in 
Household Surveys.'' Public Opinion Quarterly, 70: pp. 646-675.
13. Betts, K.R., V. Boudewyns, K.J. Aikin, C. Squire, et al. (2017). 
``Serious and Actionable Risks, Plus Disclosure: Investigating an 
Alternative Approach for Presenting Risk Information in Prescription 
Drug Television Advertisements.'' Research in Social & 
Administrative Pharmacy. doi: 10.1016/j.sapharm.2017.07.015.

    Dated: March 7, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-04996 Filed 3-12-18; 8:45 am]
 BILLING CODE 4164-01-P