Notice2022-20623

Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment Request; Targeted Mechanism of Action Presentations in Prescription Drug Promotion

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Published
September 23, 2022

Issuing agencies

Health and Human Services DepartmentFood and Drug Administration

Abstract

The Food and Drug Administration (FDA, Agency, or we) 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.

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<title>Federal Register, Volume 87 Issue 184 (Friday, September 23, 2022)</title>
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[Federal Register Volume 87, Number 184 (Friday, September 23, 2022)]
[Notices]
[Pages 58110-58116]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2022-20623]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2021-N-1050]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Targeted Mechanism of 
Action Presentations in Prescription Drug Promotion

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is 
announcing that a proposed collection of information has been submitted 
to the Office of Management and Budget (OMB) for review and clearance 
under the Paperwork Reduction Act of 1995.

DATES: Submit written comments (including recommendations) on the 
collection of information by October 24, 2022.

ADDRESSES: To ensure that comments on the information collection are 
received, OMB recommends that written comments be submitted to <a href="https://www.reginfo.gov/public/do/PRAMain">https://www.reginfo.gov/public/do/PRAMain</a>. Find this particular information 
collection by selecting ``Currently under Review--Open for Public 
Comments'' or by using the search function. The title of this 
information collection is ``Targeted Mechanism of Action Presentations 
in Prescription Drug Promotion.'' Also include the FDA docket number 
found in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: JonnaLynn Capezzuto, Office of 
Operations, Food and Drug Administration, Three White Flint North, 10A-
12M, 11601 Landsdown St., North Bethesda, MD 20852, 301-796-3794, 
<a href="/cdn-cgi/l/email-protection#f0a0a2b1a384919696b0969491de989883de979f86"><span class="__cf_email__" data-cfemail="5c0c0e1d0f283d3a3a1c3a383d7234342f723b332a">[email&#160;protected]</span></a>.
    For copies of the questionnaire: Office of Prescription Drug 
Promotion (OPDP) Research Team, <a href="/cdn-cgi/l/email-protection#33776770415640565241505b735557521d5b5b401d545c45"><span class="__cf_email__" data-cfemail="a6e2f2e5d4c3d5c3c7d4c5cee6c0c2c788ceced588c1c9d0">[email&#160;protected]</span></a>.

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.

Targeted Mechanism of Action Presentations in 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.
    The Office of Prescription Drug Promotion's (OPDP) mission is to 
protect the public health by helping to ensure that prescription drug 
promotion is truthful, balanced, and accurately communicated. OPDP's 
research program provides scientific evidence to help ensure that our 
policies related to prescription drug promotion will have the greatest 
benefit to public health. Toward that end, we have consistently 
conducted research to evaluate the aspects of prescription drug 
promotion that are most central to our mission. Our research focuses in 
particular on three main topic areas: advertising features, including 
content and format; target

[[Page 58111]]

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. This study will inform 
the first two topic areas, advertising features and target populations.
    Because we recognize the strength of data and the confidence in the 
robust nature of the findings are 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 home page, 
which can be found at: <a href="https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/office-prescription-drug-promotion-opdp-research">https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/office-prescription-drug-promotion-opdp-research</a>. The website includes links to the latest Federal Register 
notices and peer-reviewed publications produced by our office.
    In 2014, OPDP conducted focus groups designed to provide insights 
on how consumers and healthcare providers (HCPs), including physicians, 
nurse practitioners, and physician assistants, interpret the term 
``targeted'' in prescription drug promotional materials. Although 
diverse views were voiced, there appeared to be some tendency toward 
the impression that products with promotional materials using this term 
would be safer and more effective than other similar treatments. OPDP 
is also now conducting a nationally representative survey regarding the 
ways in which consumers and primary care physicians (PCPs) interpret 
terms and phrases commonly used in prescription drug promotional 
materials, including assessment of impressions of the terms 
``targeted'' and ``targeted mechanism of action'' (targeted MoA) (86 FR 
24867, May 10, 2021). Building upon this line of research, the proposed 
study will investigate the influence of targeted MoA claims, graphics, 
and disclosures that provide context about a drug's targeted MoA, 
utilizing an experimental design with both consumer and HCP samples. 
The experimental approach described here is intended to complement and 
augment the prior research by facilitating assessment of causality. 
Specifically, the proposed study will explore how varied targeted MoA 
presentations affect consumer and HCP understanding of the MoA of a 
drug, perception of drug benefits and risks, attention to risk 
information, and interest in the drug.
    Table 1 depicts the study design. Participants will be randomly 
assigned to one of 12 experimental conditions in which the presence 
versus absence of: (1) a targeted MoA claim, (2) a graphic depicting a 
targeted MoA, and (3) a disclosure that provides context about the 
targeted MoA of the drug are varied in a branded website for a 
fictitious prescription drug indicated to treat bladder cancer and 
cancers of the urinary tract (renal pelvis, ureter, or urethra) that 
have spread or cannot be removed by surgery. We selected cancer as the 
medical condition for study given the prevalence of targeted MoA 
presentations in promotional materials for prescription drugs indicated 
to treat various forms of cancer. Notably, there will be three 
variations related to the targeted MoA graphic: (1) no graphic, (2) an 
inaccurate graphic (graphic 1) showing only the effect of the drug on 
cancerous cells but not on healthy cells, and (3) an accurate graphic 
(graphic 2) that will show the effect of the drug on both cancerous and 
healthy cells. The design will be replicated in both the consumer and 
HCP samples with stimuli specifically created for each audience. Draft 
stimuli were informed by, but not identical to, actual targeted MoA 
presentations from a marketplace evaluation conducted under FDA 
guidance. Draft stimuli were also informed by an FDA subject matter 
expert's review. Following exposure to the stimuli, the participants 
will complete a questionnaire designed to assess relevant outcome 
measures. A copy of the questionnaire is available upon request. All 
aspects of this study will be completed online. Participation is 
estimated to take approximately 20 minutes, excluding the screener's 
time.

                                                                  Table 1--Study Design
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                      Targeted MoA graphic
                                                                                                      --------------------------------------------------
                  Sample                            Disclosure                Targeted MoA claim           Present          Present
                                                                                                         (graphic 1--     (graphic 2--        Absent
                                                                                                         inaccurate)       accurate)
--------------------------------------------------------------------------------------------------------------------------------------------------------
HCP......................................  Present.....................  Present.....................     \1\ [ssquf]          [ssquf]          [ssquf]
                                                                         Absent......................         [ssquf]          [ssquf]          [ssquf]
                                           Absent......................  Present.....................         [ssquf]          [ssquf]          [ssquf]
                                                                         Absent......................         [ssquf]          [ssquf]          [ssquf]
Consumer.................................  Present.....................  Present.....................         [ssquf]          [ssquf]          [ssquf]
                                                                         Absent......................         [ssquf]          [ssquf]          [ssquf]
                                           Absent......................  Present.....................         [ssquf]          [ssquf]          [ssquf]
                                                                         Absent......................         [ssquf]          [ssquf]          [ssquf]
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ Each [ssquf] symbol represents an experimental condition.

    For the HCP sample, we will recruit oncologists, PCPs with oncology 
experience, and nurse practitioners and physician assistants who 
specialize in oncology. We will also recruit a general population 
sample of adult volunteers 18 years or older for the consumer sample. A 
general population, rather than a diagnosed consumer sample, was 
selected because of concerns about being able to recruit enough 
participants for this particular study if we selected a cancer-specific 
sample.
    We will ask consumers to consider a hypothetical scenario in which 
they have recently been diagnosed with cancer and are actively looking 
for available treatments. HCPs will be asked to consider a scenario in 
which they are actively looking for available treatments for a patient 
who has been diagnosed with cancer. We will also ask consumers if they 
have ever been diagnosed with cancer. HCP participants will be drawn

[[Page 58112]]

from online HCP panels, and general population consumer participants 
will be drawn from online consumer panels. Informed by power analyses, 
we will recruit a sample of 540 HCPs and 540 consumers for the main 
study.
    In the Federal Register of October 28, 2021 (86 FR 59736), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. FDA received five comments that were 
Paperwork Reduction Act (PRA) related. Within the submissions, FDA 
received multiple comments that the Agency has addressed in this 
notice. For brevity, some public comments are paraphrased and, 
therefore, may not state the exact language used by the commenter. All 
comments were considered even if they were not fully captured by our 
paraphrasing in this document. One submission (ID number FDA-2021-N-
1050-0002) was read and considered but was outside the scope of the 
research and is not addressed further. Comments and responses are 
numbered here for organizational purposes only.
    (Comment 1) One comment stated that FDA has already investigated 
how HCPs and consumers interpret the terms ``targeted'' and ``targeted 
mechanism of action.''
    (Response 1) Prior qualitative research \1\ looked at how consumers 
and HCPs interpret the term ``targeted'' in prescription drug 
promotional materials. This initial qualitative research suggested that 
products using the term ``targeted'' may appear safer or more effective 
than other similar treatments but did not fully explore the 
implications of those interpretations. Robust empirical evidence is 
needed to understand how complex concepts, such as ``targeted'' and 
``targeted MoA,'' are interpreted or whether they lead to inaccurate 
inferences about a drug's efficacy and side effects when presented to 
consumers and HCPs in prescription drug promotion. The present research 
seeks to extend previous studies by investigating the effects of 
including a graphic and by exploring whether the inclusion of a 
disclosure statement can help to clarify the information. It is 
possible that the presence of targeted MoA graphics affects the 
impressions of the product, which we are assessing in this study. It is 
also possible that any inflated perceptions consumers or HCPs may have 
based on the MoA claim or graphics can be adjusted by adding a 
disclosure. These are the questions this research is aiming to address 
through an experimental design. We conducted a literature review, which 
found that only two published articles (Refs. 1 and 2) have focused on 
assessing the impact of exposure to MoA presentations in prescription 
drug promotion. We also conducted a marketplace evaluation, which found 
that these types of presentations are widespread in the prescription 
drug promotion marketplace. Together, this preliminary work highlights 
the importance of this study and the need for experimental research 
that examines the effect of targeted MoA presentations in prescription 
drug promotion on both consumers and HCPs.
---------------------------------------------------------------------------

    \1\ See ``Focus Groups to Investigate Specific Terminology in 
Prescription Drug Promotion (completed in 2014),'' available at 
<a href="https://www.fda.gov/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cder/ucm090276.htm">https://www.fda.gov/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cder/ucm090276.htm</a>.
---------------------------------------------------------------------------

    (Comment 2) Two comments proposed recruiting cancer patients rather 
than general population consumers because, according to one comment, 
cancer patients are more likely to be exposed to promotional materials 
regarding cancer products and may be more familiar with cancer-related 
terms than the general population. The comments also suggested that 
being diagnosed with a life-threatening illness may influence 
perception of risk/benefit and interest in a drug. One comment 
encouraged the Agency to look for ways to mitigate such bias, and the 
other specifically proposed that the Agency focus the research on a 
target consumer respondent sample of those who have had a cancer 
diagnosis and allow the screening criteria to straddle across multiple 
cancer diagnoses.
    (Response 2) We chose a general population sample because of 
concerns about being able to recruit enough participants if we selected 
a cancer-specific sample. However, we agree that in a future study, a 
small, carefully designed replication study with cancer patients could 
be valuable. We will also ask participants if they have been diagnosed 
with cancer and control for any impact that a diagnosis of prior cancer 
may have.
    (Comment 3) One comment objected that access to the specific study 
stimuli and questionnaire was not provided.
    (Response 3) We have described the purpose of the study, the 
design, and the population of interest and have provided the 
questionnaire to numerous individuals upon request. We provided the 
disclosure language in the questionnaire. 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 our research.
    (Comment 4) Two comments suggested that the research assumes that 
all targeted MoA claims that do not include a discussion of off-target 
effects are misleading and that it is misleading to suggest that 
targeted therapies are safer or more effective. The comments noted that 
this assumption would be overly broad and simplified and may result in 
biased results.
    (Response 4) This research does not assume that any specific 
presentation is or is not misleading. Rather, this research aims to 
understand whether variations in MoA presentations of a targeted drug 
(e.g., presenting an inaccurate graphic depicting a drug's MoA without 
a disclosure relative to an accurate graphic depicting the MoA) may 
affect consumer and HCP perceptions of the drug. In this way, the 
research will provide more information to help determine whether these 
audiences are misled by the tested presentations.
    (Comment 5) Two comments focused on the proposed graphics. One 
expressed concern about the ability of a graphic to depict a targeted 
MoA accurately (particularly as it refers to the impact on off-target 
healthy cells) and to convey a truthful and non-misleading 
representation. The other comment proposed changes to the inaccurate 
graphic in terms of how it depicted healthy and cancer cells.
    (Response 5) We tested candidate graphics in cognitive interviews 
to confirm that the audience interpreted the graphics as intended. The 
graphics were also reviewed by medical professionals, and we consulted 
with a doctoral-trained researcher who publishes extensively on the 
effects of graphic presentations in health communication and 
advertising.
    (Comment 6) One comment noted that it is unclear what proportion of 
the sample will be oncologists versus PCPs with oncology experience. 
The comment also stated that while PCPs may have a role in the cancer 
patient's journey and may provide input along the way to diagnosis, as 
well as during the management phase of treatment, they are not routine 
decision makers for new treatments or treatment changes.
    (Response 6) HCPs of all types are exposed to prescription drug 
promotion. Depending on location (e.g., rural areas) and type of 
clinical setting, some non-oncologists may consider oncologic 
prescription drugs to treat their patients. We agree that oncologists 
are the most relevant population to study in this research. However, we 
also want to know whether specific education and experience influence 
the processing of claims, graphics, and disclosures. We

[[Page 58113]]

intend to use PCPs as a control group to understand whether specific 
advanced training influences the understanding of MoA claims, graphics, 
and associated disclosures. Further, including PCPs with oncology 
experience alongside oncologists has yielded useful data in prior 
studies (Ref. 3). The sample will be equally distributed across 
oncologists, PCPs with oncology experience, and nurse practitioners and 
physician assistants with oncology experience.
    (Comment 7) One comment stated that the study should only recruit 
nurse practitioners and physician assistants who specialize in 
oncology.
    (Response 7) We agree. Only nurse practitioners and physician 
assistants who specialize in oncology are eligible for the study.
    (Comment 8) One comment noted that the instructions at the top of 
the questionnaire ask participants to ``make your best guess'' based on 
the web page they just viewed. The comment stated that respondents 
should not be asked to guess as their response and argued that these 
instructions undermine the importance of the participants' answers.
    (Response 8) The instructions are displayed before perceived 
efficacy and risk questions where consumer participants are told, 
``Most people don't know how a prescription drug will affect them until 
they've taken the drug. But we'd like you to make your best guess based 
on the web page you just saw. Please answer the following questions 
based on what you saw on the web page.'' HCPs are told, ``Please answer 
the following questions based on what you saw on the web page rather 
than prior knowledge of this class of medications.''
    These instructions have been cognitively tested in prior studies, 
as well as in the present study, and we found no evidence that these 
instructions undermined the perceived importance of participants' 
answers. Instead, the instructions helped to indicate that we wanted 
participants to form an opinion and that they did not need to base 
their opinion on prior knowledge to do so.
    (Comment 9) One comment suggested that the recall questions 
(questions 6 through 11) and especially the ``foil'' responses could 
bias the responses to the questions that follow them and recommended 
locating the recall questions after other questions.
    (Response 9) We always approach question ordering carefully, 
attempting to balance several considerations, including the reduction 
of bias from one question to another, the flow, and the importance of 
each item. In this case, we are prioritizing measures of specific claim 
comprehension over other more general questions in our questionnaire, 
which is why questions 6 through 11 are placed earlier in the 
questionnaire. Answering recall and comprehension questions first will 
allow consumers and HCPs to provide a more accurate response and will 
allow us to better understand whether the information was comprehended. 
We did not encounter any issues with recall questions influencing 
responses to questions found later in the survey during cognitive 
interviews.
    (Comment 10) One comment recommended using a consistent scale 
throughout the survey. Another suggested changing questions 12, 13, 14, 
16, 17, 18, 19, 20, 22, and 23 to 7-point scales to add a midpoint.
    (Response 10) We use true/false/don't know or yes/no/don't know 
response options for the comprehension questions and Likert-type scales 
for perceptions and opinion questions. Using one scale throughout the 
survey would not necessarily provide better data. For nearly all 
Likert-type questions, we use 6-point scales with the endpoints 
labeled. Some of these questions with Likert-type scales are validated 
questions; for these, we have maintained the response options from the 
validated measures. Other questions were altered from validated 
measures, and similarly, we preferred to maintain the Likert-type 
scales that the original measure had. We will change question 5 from a 
7-point to a 6-point scale to increase consistency. We will retain the 
5-point scales with all response options labeled for the two validated 
scales for beliefs about medications and trust in prescription drug 
materials.
    Regarding the inclusion of a midpoint, this is a matter of debate 
in the literature and has never been resolved. Based on input from 
cognitive interviews and in response to public comments, we will be 
adding a neutral point to the comparative efficacy and risk questions 
(i.e., questions 17 through 23), which will change these questions to 
be 7-point response options with endpoints and midpoint labeled.
    (Comment 11) Two comments stated that the 6-point scales do not 
allow the respondent to pick neither agree/disagree/unknown. One 
comment noted that this is a concern for most 6-point scale questions 
but particularly for questions 17 through 23, which compare the study 
drug to other medications. The comments recommended either an anchored 
neutral middle point on the scale or a box for uncertain/do not know 
responses.
    (Response 11) There are benefits and drawbacks to including a 
neutral or ``no reaction'' response in survey research, and the 
decision to use a neutral midpoint depends on the goal of the measures 
(Refs. 4 and 5). For questions assessing comprehension of the MoA 
claim, we included a ``do not know'' option as this response would 
indicate some level of uncertainty about the MoA, and that uncertainty 
itself would be meaningful and actionable information. However, when 
assessing perceptions and attitudes about the claim, graphic, or 
disclosure, our objective is to force a selection. Inclusion of a 
neutral response option in these instances could potentially encourage 
satisficing--cuing participants to select a neutral response when there 
is uncertainty (Ref. 7). For the comparative risk and efficacy 
questions (questions 17 through 23), we will include a midpoint based 
on results from cognitive interviews; however, these interviews did not 
point to the need to include a midpoint for the other questions.
    (Comment 12) Questions 17 through 23 ask about the efficacy and 
risks of the study drug compared to other prescription drugs for the 
same indication. One comment contended that, without prior knowledge of 
the efficacy and risks of the prescription drugs on the market, it 
would be difficult for respondents to make a fully informed conclusion. 
Another comment asserted that the comparative risk and efficacy 
questions should be revised to establish a clear comparator, such as 
chemotherapy. Finally, a comment recommended removing these questions 
as consumers should not be assessing a drug's safety or efficacy 
compared to other drugs.
    (Response 12) There are instances in the clinical setting when 
consumers will discuss the safety and risk information of a drug 
compared to others (e.g., if a patient switches from one drug to 
another or if a family member asks the consumer to talk to their doctor 
about another drug). We acknowledge that in a clinical setting, 
patients and HCPs may use additional information to make decisions 
about how a drug compares to another. However, the intent of questions 
17 through 23 is to understand whether exposure to different 
presentations of the MoA claim, graphics, and disclosure results in 
different comprehension or perceptions, such as perception of 
comparative risks and efficacy. Except for the varied presentations, 
all participants will have the same level of information regarding the 
MoA of the drug. So, we would expect that all

[[Page 58114]]

participants would be equally informed of the drug, and differences 
among study conditions could be attributed to the experimental 
manipulations. Additionally, any subjective experiences outside the 
experiment setting should be evenly distributed across study conditions 
as a function of random assignment; therefore, they should not have any 
impact on the outcomes of the study. Still, cognitive interviews 
indicated that HCPs and consumers preferred that a midpoint be added to 
the response scale for these questions, which we added in the revised 
questionnaire. Based on cognitive interviews, we also revised the 
questions to include the phrase ``compared to other similar 
prescription drugs that are for/treat bladder cancer.'' We will also 
review these questions and make any necessary adjustments based on pre-
testing results.
    (Comment 13) One comment stated that the questionnaire does not 
consider the HCP respondents' baseline understanding or expectations of 
targeted treatments.
    (Response 13) We expect that any knowledge or expectations of 
targeted treatments that consumers and HCPs already have outside of the 
experiment setting should be evenly distributed across study conditions 
as a function of random assignment; therefore, observed differences 
between conditions are unlikely to be caused by these individual 
differences. However, we added an item that assesses HCPs' knowledge of 
targeted therapies for cancer treatments.
    (Comment 14) One comment encouraged FDA to disseminate all final 
results of completed research related to this topic.
    (Response 14) FDA's research is documented on our homepage, which 
can be found at <a href="https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/office-prescription-drug-promotion-opdp-research">https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/office-prescription-drug-promotion-opdp-research</a>. The 
website includes links to the latest Federal Register notices and peer-
reviewed publications produced by our office. The Agency also 
anticipates disseminating the results of this study after the final 
analyses of the data are completed. The exact timing and nature of any 
such dissemination has not been determined, but dissemination of 
research results often occurs through presentations at trade and 
academic conferences, publications, articles, and postings on FDA's 
website.
    (Comment 15) One comment recommended that certain populations, such 
as those who work in pharmaceutical marketing or for the U.S. 
Department of Health and Human Services (HHS), be excluded from the 
study.
    (Response 15) We agree. Participants will be excluded from 
participation if they work for a pharmaceutical, advertising, or market 
research company or are employed by HHS.
    (Comment 16) One comment recommended that participants who are 
unable to recall key elements of the stimuli, such as indication, risk 
elements, presence of claim, and presence of disclaimers, be excluded 
from the study because they are not able to appropriately assess the 
MoA presentations.
    (Response 16) The fact that a consumer or HCP is not able to recall 
certain information does not mean they did not see that information or 
subconsciously process it (Ref. 6). Therefore, we do not plan to 
exclude anyone based on their self-reported recall of elements in the 
stimuli.
    (Comment 17) One comment suggested that participants should be 
asked questions 30 through 34 as part of a pre-test and be stratified 
based on their responses.
    (Response 17) Typically, stratified randomization is used if there 
are prognostic variables that correlate with outcome measures and 
researchers are concerned about such factors not being evenly 
distributed across groups (Ref. 8). We have no reason to expect that 
the aforementioned factors would have a strong association with the 
outcome measures, nor do we have reason to believe that we will not 
achieve adequate balance of prognostic variables given the large sample 
size proposed for this study (Ref. 8). Random assignment will help to 
produce groups that are, on average, probabilistically similar to each 
other. Because randomization eliminates most other sources of 
systematic variation, we can be reasonably confident that any effect 
that is found is the result of the intervention and not some 
preexisting differences between the groups (Ref. 9). However, we have 
included questions 30 through 34 to assess the association of factors 
such as health literacy, prior cancer diagnosis, or familiarity with 
cancer treatment options with our outcomes and statistically control 
for those variables if necessary.
    (Comment 18) One comment suggested that in order to ensure that 
differences in risk assessment across stimuli are due to the 
manipulation of MoA information, the prominence of the risk 
presentation should be standardized across the 12 versions of the 
stimuli and displayed in accordance with FDA's guidance document 
entitled ``Presenting Risk Information in Prescription Drug and Medical 
Device Promotion.'' \2\ The comment also encouraged the use of 
qualifiers to delineate which side effects are considered serious.
---------------------------------------------------------------------------

    \2\ The draft guidance for industry ``Presenting Risk 
Information in Prescription Drug and Medical Device Promotion'' (May 
2009) is available on the FDA guidance web page at <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents">https://www.fda.gov/regulatory-information/search-fda-guidance-documents</a>. 
When finalized this guidance will represent FDA's thinking on this 
issue.
---------------------------------------------------------------------------

    (Response 18) In creating the stimuli, we created one web page that 
was the basis for all the stimuli. The risk presentation was 
standardized across the experimental conditions, and we kept FDA's 
guidance in mind when displaying stimuli. Regarding the suggested use 
of qualifiers to delineate which side effects are considered 
``serious,'' we again note that we kept FDA's guidance in mind with 
respect to the risk presentation.
    (Comment 19) One comment noted that the disclosure for patients 
should be reworded as follows to prevent implied bias: ``[Drug X] 
delivers medicine directly to cancer cells and can also harm healthy 
cells.''
    (Response 19) We revised the statement to read ``[Drug X] could 
also affect healthy cells.'' With this change, the consumer disclosure 
is consistent with the content of the disclosure shown to HCPs.
    (Comment 20) One comment asserted that most promotional materials 
in the real world qualify MoA statements with language mirroring the 
labeling (e.g., ``Pre-clinical studies demonstrate . . .'') and 
recommended that the research materials be updated to include similar 
qualifying language.
    (Response 20) The addition of such language may create an imbalance 
of information across the various experimental conditions and could 
confound interpretation of the results. As such, we did not include the 
qualifying language mentioned above.
    (Comment 21) One comment suggested that study participants should 
be allowed to refer back to the product website as often as needed 
rather than only being permitted to view it once.
    (Response 21) As a practice, we often purposely do not permit study 
participants to refer back to the product website as often as needed 
for these types of studies. Rather, for this study, we will instruct 
participants to read the website carefully and alert them that they 
will be answering several questions about the content that they just 
saw and that they cannot return to the website. The goal of this study 
is not to assess participants' comprehension of verbatim information in 
the stimuli, for which

[[Page 58115]]

repeated exposures to stimuli may be more appropriate in another study. 
Rather, the present study is interested in gist understanding of the 
information. Allowing for multiple exposures to the stimuli could 
potentially influence study outcomes and confound interpretation of the 
study results. A large literature supports presence of a ``mere 
exposure effect'' in social science research, where more exposure 
enhances processing and increases positive affect toward stimuli (Refs. 
10 and 11).
    (Comment 22) One comment recommended removing question 16 (i.e., 
risk-benefit tradeoff) for consumers because consumers may not have the 
experience or background to assess a drug's benefit-risk profile. The 
comment also suggested that this question ignores the role of 
prescribers in informing patients of the relevant risks and benefits of 
prescription medications.
    (Response 22) We disagree that consumers do not form their own 
perceptions about risk-benefit tradeoffs after seeing direct-to-
consumer (DTC) promotional materials and before any discussion with an 
HCP. Consumers often wish to participate in shared decision making with 
HCPs when selecting prescription drugs and may request specific 
prescription drugs from their HCPs based on promotions they have seen 
in the marketplace. Because the information consumers receive through 
DTC prescription drug promotion can impact these requests, it is 
important to investigate how the information in prescription drug 
promotional pieces impacts consumer attention, understanding, and 
perceptions. In addition, the purpose of these questions is to assess 
perceived benefit and risk based on the promotional material shown. The 
question includes instructions indicating that judgments should be 
reached based on the information on the prescription drug website. As 
such, we plan to ask participants about their perceptions of the risk-
benefit tradeoff using question 16, which is a common and validated 
item in DTC research.
    FDA estimates the burden of this collection of information as 
follows:

                                  Table 2--Estimated Annual Reporting Burden 1
----------------------------------------------------------------------------------------------------------------
                                 Number of       Number of
          Activity             respondents 2   responses per   Total annual     Average burden per   Total hours
                                                respondent       responses          response 3
----------------------------------------------------------------------------------------------------------------
Pretest:
    General population:                  528               1             528  0.08 (5 min.)........         42.2
     pretest screener
     completes (assumes 75%
     eligible).
    General population:                  396               1             396  0.33 (20 min.).......        130.7
     number of completes,
     pretest.
    HCP: pretest screener                660               1             660  0.08 (5 min.)........         52.8
     completes (assumes 60%
     eligible).
    HCP: number of                       396               1             396  0.33 (20 min.).......        130.7
     completes, pretest.
Main Study:
    General population:                  792               1             792  0.08 (5 min.)........         63.4
     number of main study
     screener completes
     (assumes 75% eligible).
    General population:                  594               1             594  0.33 (20 min.).......        196.0
     number of completes,
     main study.
    HCP: number of main                  990               1             990  0.08 (5 min.)........         79.2
     study screener
     completes (assumes 60%
     eligible).
    HCP: number of                       594               1             594  0.33 (20 min.).......        196.0
     completes, main study.
                             -----------------------------------------------------------------------------------
        Total...............  ..............  ..............  ..............  .....................          891
----------------------------------------------------------------------------------------------------------------
1 There are no capital costs or operating and maintenance costs associated with this collection of information.
2 As with most online and mail surveys, it is always possible that some participants are in the process of
  completing the survey when the target number is reached and that those surveys will be completed and received
  before the survey is closed out. To account for this, we have estimated approximately 10 percent overage for
  both samples in the study.
3 Burden estimates of less than 1 hour are expressed as a fraction of an hour in decimal format.

II. References

    The following references marked with an asterisk (*) are on display 
at the Dockets Management Staff (see ADDRESSES) and are available for 
viewing by interested persons between 9 a.m. and 4 p.m., Monday through 
Friday; they also are available electronically at <a href="https://www.regulations.gov">https://www.regulations.gov</a>. References without asterisks are not on public 
display at <a href="https://www.regulations.gov">https://www.regulations.gov</a> because they have copyright 
restriction. Some may be available at the website address, if listed. 
References without asterisks are available for viewing only at the 
Dockets Management Staff. 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. O'Donoghue, A.C., Williams, P.A., Sullivan, H.W., et al. 
``Effects of Comparative Claims in Prescription Drug Direct-to-
Consumer Advertising on Consumer Perceptions and Recall.'' Social 
Science & Medicine, 120:1-11, 2014.
*2. Sullivan, H.W., O'Donoghue, A.C., Gard Read, J., et al. 
``Testimonials and Informational Videos on Branded Prescription Drug 
websites: Experimental Study to Assess Influence on Consumer 
Knowledge and Perceptions.'' Journal of Medical internet Research, 
20(1):e13, 2018.
3. Boudewyns, V., O'Donoghue, A.C., Paquin, R.S., et al. ``Physician 
Interpretation of Data of Uncertain Clinical Utility in Oncology 
Prescription Drug Promotion.'' The Oncologist, 26(12):1071-1078, 
2021.
4. Moors, G. ``Exploring the Effect of a Middle Response Category on 
Response Style in Attitude Measurement.'' Quality & Quantity, 
42(6):779-794, 2008.
5. Sturgis, P., Roberts, C., and Smith, P. ``Middle Alternatives 
Revisited: How the Neither/nor Response Acts as a Way of Saying `I 
Don't Know?''' Sociological Methods & Research, 43(1):15-38, 2014.
6. Shapiro, S. and Krishnan, H.S. ``Memory-Based Measures for 
Assessing Advertising Effects: A Comparison of Explicit and Implicit 
Memory Effects.'' Journal of Advertising, 30(3):1-13, 2001.
7. Krosnick, J.A. ``Questionnaire Design.'' In: Vannette, D., 
Krosnick, J. (eds). The Palgrave Handbook of Survey Research (pp. 
439-455). Palgrave Macmillan, Cham, 2018.
8. Friedman, L.M., Furberg, C.D., DeMets, D.L., et al. Fundamentals 
of Clinical Trials. 5th ed. New York, NY: Spring Science-Business 
Media, 1998.
9. Fisher, R.A. The Design of Experiments. Edinburgh, United 
Kingdom: Oliver & Boyd, 1935.
10. Bornstein, R.F. ``Exposure and Affect: Overview and Meta-
analysis of Research, 1968-1987.'' Psychological Bulletin, 
106(2):265-289, 1989.

[[Page 58116]]

11. Bornstein, R.F. and D'Agostino, P.R. ``The Attribution and 
Discounting of Perceptual Fluency: Preliminary Tests of a Perceptual 
Fluency/Attributional Model of the Mere Exposure Effect.'' Social 
Cognition, 12(2):103-128, 1994.

    Dated: September 19, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-20623 Filed 9-22-22; 8:45 am]
BILLING CODE 4164-01-P


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