Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment Request; Examination of Secondary Claim Disclosures and Biosimilar Disclosures in Prescription Drug Promotional Materials, 50888-50894 [2021-19690]

Agencies

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

[Federal Register Volume 86, Number 174 (Monday, September 13, 2021)]
[Notices]
[Pages 50888-50894]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-19690]



[[Page 50888]]

-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2020-N-1307]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Examination of 
Secondary Claim Disclosures and Biosimilar Disclosures in Prescription 
Drug Promotional Materials

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

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

DATES: Submit written comments (including recommendations) on the 
collection of information by October 13, 2021.

ADDRESSES: To ensure that comments on the information collection are 
received, OMB recommends that written comments be submitted to https://www.reginfo.gov/public/do/PRAMain. Find this particular information 
collection by selecting ``Currently under Review--Open for Public 
Comments'' or by using the search function. The title of this 
information collection is ``Examination of Secondary Claim Disclosures 
and Biosimilar Disclosures in Prescription Drug Promotional 
Materials.'' 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, 10 a.m.-12 p.m., 
11601 Landsdown St., North Bethesda, MD 20852, 301-796-7726, 
[email protected].

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

Examination of Secondary Claim Disclosures and Biosimilar Disclosures 
in Prescription Drug Promotional Materials

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 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 areas: Advertising features and target 
populations.
    Because we recognize that the strength of data and the confidence 
in the robust nature of the findings is improved by utilizing the 
results of multiple converging studies, we continue to develop evidence 
to inform our thinking. We evaluate the results from our studies within 
the broader context of research and findings from other sources, and 
this larger body of knowledge collectively informs our policies as well 
as our research program. Our research is documented on our homepage, 
which can be found at: https://www.fda.gov/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cder/ucm090276.htm. The website 
includes links to the latest Federal Register notices and peer-reviewed 
publications produced by our office. The website maintains information 
on studies we have conducted, dating back to a survey on direct-to-
consumer (DTC) advertisements conducted in 1999.
    The purpose of this research is to build on prior FDA research on 
the topic of disclosures by examining the impact of disclosures of two 
different types of information, detailed later in this notice. The 
literature on disclosures suggests their effectiveness is subject to 
format, design, and audience factors, among other things (Ref. 1). For 
example, research on consumer attitudes has found some people believe 
that FDA evaluates certain dietary supplement claims despite the 
presence and consumer awareness of language required by the Dietary 
Supplement Health and Education Act, which clearly states that FDA has 
not evaluated those claims (Refs. 2 and 3). In the context of 
prescription drug promotion, there is initial evidence that--when 
noticed--disclosures may effectively convey important information 
(Refs. 4 to 6); however, what role disclosures may play in educating or 
correcting misunderstanding warrants further investigation.
    In the new study proposed here, the first type of disclosed 
information we will examine is clinical benefit information based on a 
secondary endpoint reported in a product's approved labeling (a 
secondary claim). In some cases, truthful and non-misleading 
presentations about secondary endpoints in well-designed clinical 
studies can provide reliable information about treatment effects that 
may be distinct from the treatment effects described in the product's 
indication statement. For example, a product may be indicated to treat 
a specific type of cancer based on a primary endpoint of survival. 
However, a secondary endpoint in the study of that product may provide 
data about an additional distinct benefit, such as functional status.
    Phase 1 of the proposed research will examine the impact of adding 
a disclosure about a secondary claim in DTC and healthcare provider 
(HCP)-directed promotion in the context of a prescription drug website. 
We will also examine the effect of the presence of a comparative claim 
about the secondary claim. Our proposed main outcome measures are 
perceptions of and attitudes toward the product, the secondary claim, 
and the disclosure. The pretest and main studies for Phase 1 will have 
the same design, will be conducted online, and will follow the same 
procedure. We will examine four levels of secondary claim disclosure to 
explore the effects of disclosing that the secondary benefit is not one 
of the indicated uses of the product (e.g., not a treatment for [the 
secondary benefit

[[Page 50889]]

claim], quantitative information about claim, not a treatment for 
[claim] and quantitative information about claim, or no disclosure), 
and two levels (presence or absence) of a comparative element regarding 
the secondary claim, for a total of eight experimental conditions (see 
table 1). Participants will be randomly assigned to one of these 
conditions; they will view one version of a website. This 4 x 2 design 
will be replicated across two target populations (HCPs and consumers).

                                                              Table 1--Phase 1 Study Design
                        [Phase 1: Secondary Claim Disclosure by Comparative Secondary Claim in Online Prescription Drug Websites]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                    Secondary claim disclosure
                                                                         -------------------------------------------------------------------------------
                                                                                                                   ``Drug X is not a
                                                                                                ``In a clinical      treatment for
                                                                                                    trial,        [claim]'' AND ``In
                       Comparative secondary claim                         ``Drug X is not a     participants      a clinical trial,  None (no secondary
                                                                             treatment for       [quantitative       participants      claim disclosure)
                                                                               [claim]''        information] on      [quantitative
                                                                                                   Drug X''         information] on
                                                                                                                       Drug X''
--------------------------------------------------------------------------------------------------------------------------------------------------------
HCPs:
    Present: Compared to [xx] on Drug Y.................................
    Absent..............................................................
Consumers:
    Present: Compared to [xx] on Drug Y.................................
    Absent..............................................................
--------------------------------------------------------------------------------------------------------------------------------------------------------

    The second, independent phase of the proposed research will examine 
disclosures about a biosimilar product. In both consumer and HCP 
audiences, we will assess the impact of a disclosure designating the 
product as a biosimilar as well as varying basic factual statements 
about biosimilars. Phase 2 will examine the impact of: (1) Adding a 
disclosure designating the product as a biosimilar; (2) adding general 
informational statements about biosimilars; and (3) naming a reference 
product. This approach allows us to examine the effect of disclosing 
biosimilar status; examines the additive effect of including one, two, 
or three additional basic statements of information about biosimilars; 
and measures the effect of naming the reference product. Our proposed 
main outcome measures are perceptions of and attitudes toward the 
biosimilar product and the disclosure.
    We propose to examine seven different disclosure conditions plus a 
control with no disclosure for a total of eight test conditions. As a 
baseline, each of the seven disclosure conditions will include a 
statement that the drug is a biosimilar. Six of the seven disclosure 
conditions will include this baseline statement and will vary the 
amount of additional basic factual information about biosimilar 
products in the following way: (1) Two of the six conditions have the 
baseline + statement A; (2), two of the six conditions have the 
baseline + statement A + statement B; and (3) two of the six conditions 
have the baseline + statement A + statement B + statement C. Moreover, 
three of the six disclosure conditions will name the specific reference 
product while the other three will refer to a reference product 
generally (for example, ``This biosimilar is a biological product that 
is highly similar to and has no clinically meaningful differences from 
an existing FDA-approved reference product''). The wording of the 
disclosure will be tailored to the audience; for example, the 
disclosures for the consumer audience will avoid technical terms. A 
control condition will also be included in which no biosimilar 
statement or additional information disclosure is presented.
    The pretest and main studies for Phase 2 will have the same design, 
will be conducted online, and will follow the same procedure. Both 
phases will be conducted concurrently. Sample sizes were determined on 
the basis of power analysis that will allow us to detect medium effect 
sizes.
    In the Federal Register of July 7, 2020 (85 FR 40659), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. FDA received eight submissions. Three 
submissions (regulations.gov tracking numbers 1k4-9hoh-uskf, 1k4-9itu-
fj33, and 1k4-9its-ko9f) were outside the scope of the research and are 
not addressed further. Within the remaining five submissions, FDA 
received multiple comments that the Agency has addressed below. For 
brevity, some public comments are paraphrased and therefore may not 
reflect the exact language used by the commenter. We assure commenters 
that the entirety of their comments was considered, even if not fully 
captured by our paraphrasing in this document. The following acronyms 
are used here: HCP = healthcare provider; FDA and ``The Agency'' = Food 
and Drug Administration; DTC = direct-to-consumer; OPDP = FDA's Office 
of Prescription Drug Promotion.
    (Comment 1) Two comments were supportive of the study, and one 
comment was supportive of the study's inclusion of both HCP and 
consumer samples.
    (Response 1) We thank the commenters for their support of the 
research.
    (Comment 2) One comment asserted that FDA has not made the stimuli 
available for public comment.
    (Response 2) 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. In our research proposals, we describe the 
purpose of the study, the design, the population of interest, and the 
estimated burden.
    (Comment 3) Two comments recommended FDA ensure the wording of the 
stimuli in both phases is appropriate to each audience (HCP and 
consumer), and one comment suggested FDA partner with a health literacy 
organization.
    (Response 3) We assessed understanding of both the consumer and 
provider versions of statements through in-depth cognitive interviews 
and will also do so in our survey. Findings from our cognitive 
interviews suggest that most consumers understood the gist of this 
information, although they were not always familiar with some 
terminology.

[[Page 50890]]

The stimuli in both phases use language appropriate to each sample and, 
where possible, use plain language in the consumer versions for greater 
clarity. We crafted the statements about biosimilars using terminology 
from FDA's Biosimilar Basics Patient Materials (https://www.fda.gov/drugs/biosimilars/patient-materials). However, when examining 
perceptions around complex concepts, such as biosimilars, plain 
language substitutes for certain terms are not always available.
    (Comment 4) One comment suggested we measure diabetes and obesity 
comorbidities of the Phase 1 consumer sample. One comment suggested we 
restrict the Phase 2 sample to consumers who have rheumatoid arthritis 
(RA), half of whom are being treated with a biologic for that 
condition, and one comment suggested we only sample rheumatologists.
    (Response 4) In Phase 1 we are measuring participants' self-
reported diagnosis of type 2 diabetes, knowledge about the disease and 
treatments for type 2 diabetes and weight loss, and prior experience 
with type 2 diabetes and weight loss treatment. These will be used as 
covariates in the analyses, where appropriate.
    With respect to the suggestion to limit the sample to diagnosed 
consumers and rheumatologists in Phase 2, there are several factors to 
consider. Diagnosed sample participants are likely to be more motivated 
to read the ad because it is relevant to their medical condition. On 
the other hand, participants in that sample are also more likely to be 
familiar with treatments for their condition and bring with them prior 
knowledge that may influence their responses. As in Phase 1, we will 
assess treatment familiarity and diagnosis amongst our general 
population sample and control for those variables. While we understand 
that the Phase 2 topic may be relevant for specialists, and we do often 
include specialists in our research, we chose not to limit our HCP 
sample. Recruiting from a wider HCP sample is more reflective of the 
reality of the healthcare environment where patients interact with HCPs 
across multiple specialties and expertise. Further, specialists make up 
a small proportion of HCPs, which makes them harder to recruit. In 
2020, for example, the proportion of specialists representing each 
specialty area ranged from 3 percent (endocrinologists) to 17 percent 
(emergency medicine specialists) (Ref. 7). These data demonstrate that 
the pool of potentially eligible specialists is limited.
    (Comment 5) One comment suggested we focus the study on patients 
rather than HCPs, as the knowledge levels of patients is low, or 
perhaps conduct separate but parallel studies of both HCPs and 
patients.
    (Response 5) The study will be conducted among two separate 
populations, consumers from the general population and HCPs. As shown 
in table 1, the study design incorporates parallel arms for consumers 
and HCPs.
    (Comment 6) One comment suggested FDA ensure a sufficient sample 
size to conduct rigorous statistical analysis.
    (Response 6) We conducted a power analyses to determine the sample 
size per study arm and will have a sufficient sample to rigorously test 
our research questions.
    (Comment 7) Two comments suggested studying comparative claims in a 
separate study to reduce participant burden and confusion.
    (Response 7) Our proposed design examines the impact of adding 
comparative and quantitative information to the disclosure of interest 
(see table 1). Each participant will see only one claim. Because these 
variables are fully crossed in the design, we will be able to examine 
the impact of comparative information and quantitative information 
separately.
    (Comment 8) One comment asked FDA to explain the added value and 
appropriateness of including disclosures in biosimilar product 
promotional materials. The comment cautioned that disclosures must not 
be couched in cautionary or negative terms or include statements that 
are ambiguous or of minimal relevance to patients.
    (Response 8) Currently, FDA neither requires nor prohibits 
biosimilar-related disclosures in biosimilar product promotion, and 
this research does not presuppose or reflect any established FDA 
position on their value. FDA is using this research to gather 
information to assess how certain biosimilar product disclosures, if 
they are used in promotion, could impact perceptions. Our study seeks 
to test several variations of biosimilar statements. We specifically 
examined potential negative reactions during in-depth cognitive 
interviews. Participants in our interviews expressed that the language 
was neutrally worded, and participants did not perceive the statements 
to be negative or cautionary.
    (Comment 9) One comment questioned whether there was a control 
group in the Phase 2 questionnaire and suggested a control group that 
will not identify the product as a biosimilar be included.
    (Response 9) The Phase 2 study includes a control condition where 
the promotional material does not identify the product as biosimilar.
    (Comment 10) One comment noted that the prescribing information for 
a biosimilar does not include a named reference product and questioned 
why FDA is mandating inclusion of a named reference product in 
biosimilar promotional materials.
    (Response 10) Sponsors may choose to disseminate promotion in which 
a comparator product is named. These comparative promotions exist in 
the marketplace. One purpose of Phase 2 is to examine the difference 
between a disclosure statement that includes a named comparator and one 
that refers to a comparator generally. The fact that FDA is conducting 
research that includes specific disclosures does not create a 
requirement that sponsors use any of those disclosures or any other 
requirement.
    (Comment 11) Two comments suggested concepts that should be 
conveyed in the biosimilar disclosures. One comment stressed the 
importance of the tone of the disclosure statement about biosimilars. 
The following key messages were proposed for inclusion in the study:
    1. Patients can expect that biosimilars will provide the same 
safety and effectiveness as the reference product.
    2. FDA has a rigorous review and approval process, applying the 
same high-quality standards to both biosimilars and reference products.
    3. Patients have been benefitting from the use of biosimilars for 
many years.
    The second comment suggested the study should also include an 
examination of the impact of adding additional information about the 
list of extrapolated indications, and the rationale for extrapolation 
of indications to a biosimilar product to assess impact on HCP 
perceptions.
    (Response 11) This study seeks to test several variations on 
potential biosimilar statements but does not attempt to test all 
possible statements. We decline to expand this study to test additional 
content like that suggested by the comments, but other content may be 
considered in future research. With regard to the comment about tone, 
for the disclosure variations that we will test, we examined potential 
negative reactions during in-depth cognitive interviews. Participants 
in our interviews expressed that the language was neutrally worded, and 
participants did not perceive the statements to be negative or 
cautionary. An examination of how HCPs perceive a biosimilar based on 
extrapolated indications is beyond the scope of this research. It may 
be considered in future research.

[[Page 50891]]

    (Comment 12) One comment suggested Phase 1 and Phase 2 be converted 
to separate studies.
    (Response 12) Phase 1 and Phase 2 are intended to be two separate 
studies that are being examined concurrently for efficiency. We will 
make this distinction clear in any discussion of results.
    (Comment 13) One comment recommended FDA narrow the scope of the 
research to questions within its jurisdiction and eliminate overlap 
with other ongoing research.
    (Response 13) As explained earlier, the Public Health Service Act 
authorizes FDA to conduct research relating to health information, and 
the FD&C Act authorizes FDA to conduct research relating to drugs and 
other FDA regulated products in carrying out the provisions of the FD&C 
Act. The study is within FDA's authority, and it will help to inform 
OPDP's work to help ensure that prescription drug information is 
truthful, balanced, and accurately communicated, so that HCPs and 
consumers can make informed decisions. While the comment did not 
identify any specific ongoing research as overlapping, we note that in 
general, OPDP may conduct concurrent or overlapping studies on similar 
topics to serve these goals.
    (Comment 14) One comment suggested participants be permitted to 
refer back to the stimuli while answering questions.
    (Response 14) For this study we will instruct participants to read 
the material carefully and alert them that they will be answering 
several questions about the content that they just saw. The goal of 
this study is not to assess participants' comprehension of detailed, 
verbatim information in the stimuli, for which repeated exposures to 
study stimuli may be more appropriate. Rather, our study will determine 
if experimental manipulation of the disclosure language influences 
``gist'' understanding of the information, attitudes, and perceptions 
(Ref. 8). Allowing for multiple exposures to the stimuli could 
potentially influence these outcomes. A large body of literature 
supports presence of a ``mere exposure effects'' in social science 
research, where more exposure enhances processing and increases 
positive affect towards stimuli (Refs. 9 and 10).
    (Comment 15) One comment stated the research lacks practical 
utility because it treats the secondary benefit claim as not related to 
the product's indicated uses, and the comment recommends that FDA 
revise Phase 1 of the study to reflect that secondary endpoints are not 
inherently unapproved uses and to focus instead on comprehension of 
what is a primary versus secondary endpoint in the data supporting a 
drug's approval.
    (Response 15) In this study, we are not making a generalization 
about the approval status of secondary endpoints. We are examining the 
specific case of a disclosure about a secondary endpoint that, while it 
may be related to the product's primary indication, is not in itself an 
indication for the product and was not evaluated in such a way to 
support the drawing of conclusions about the product's effect on that 
endpoint. In this scenario, a disclosure about the secondary claim may 
help the audience interpret the secondary claim and provide context. 
The purpose of this study is to evaluate such disclosures about this 
specific type of secondary claim and measure the impact on perceptions 
of and attitudes toward the product, the secondary claim, and the 
disclosure. For instance, we will vary such elements as the presence of 
quantitative information about the secondary claim and the presence of 
comparative information (see table 1 for full design). We note that 
there are examples of prescription drug ads currently in use that 
contain language similar to what we are evaluating in order to qualify 
secondary endpoints, thus highlighting the practical utility of this 
research.
    (Comment 16) One comment suggested changes to the instructions for 
Phase 2 to state that the study is intended to ``assess your 
understanding of and reactions to biosimilar biologic drug 
disclosures.''
    (Response 16) The control condition does not identify the product 
as biosimilar. To maintain the internal validity of the study and avoid 
potentially biasing participants' responses, we will keep the 
instructions as they are.
    (Comment 17) One comment suggested changing the dosage route and 
strength of the reference product to be consistent with currently 
marketed biologics.
    (Response 17) We have made this change.
    (Comment 18) Two comments asked that the name of the reference 
product be changed to one that is fictitious.
    (Response 18) We have made this change and will use a fictitious 
reference product name.
    (Comment 19) One comment suggested stratifying the sample on 
several variables. The comment suggested that obesity and diabetes 
diagnosis be considered specifically for Phase 1, as well as variables 
like disease severity, treatment history (e.g., patients who have never 
received a biologic versus biologic-experienced patients), and 
knowledge of the studied condition for both phases.
    (Response 19) 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. 11). We have no reason to believe that 
we will not achieve adequate balance of prognostic variables given the 
large sample size proposed for this study (Ref. 11). 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. 12). Our survey 
includes several questions about health and medical demographics that 
will enable us to assess their association with our outcomes and 
statistically control for them if necessary.
    (Comment 20) One comment suggested using consistent scales 
throughout the study and adding ``based on the ad you just saw'' to 
many of the questions.
    (Response 20) As suggested, we have added statements in the 
instructions for respondents to answer based on the promotion they 
``just saw'' for clarification. Where possible, we have used validated 
measures and have retained the scale endpoints of those measures. We do 
not believe that these varied types of questions will pose difficulties 
for respondents as we did not find evidence of difficulties in 
cognitive testing.
    (Comment 21) One comment suggested deleting or revising Phase 1 
Questions 4 to 7 to focus on whether the participant understands that 
the secondary use is linked to the approved primary indication.
    (Response 21) Our collection of constructs and measures, grounded 
in behavioral theory (Refs. 1 to 3), assesses perceptions, attitudes, 
understanding, and intentions around prescription drug disclosures. 
Based on cognitive testing, we have removed these questions.
    (Comment 22) One comment suggested deleting Phase 1 Questions 9, 
15, and 16 because they deal with the practice of medicine.
    (Response 22) The intent of Question 9 is to assess understanding 
of the secondary claim disclosure, which explains that even though the 
drug is not indicated for weight loss, that it can help some people 
lose weight. Based on

[[Page 50892]]

cognitive testing, we have revised the question to more specifically 
assess potential misperceptions of the claim; ``[drug name] is for 
weight loss'' Questions 15 and 16 are intended to assess perceptions 
about the magnitude of the drug's benefit--with regard to both the 
indication (reduction in A1C levels) and the secondary claim (weight 
loss)--based on the information in the website. Based on cognitive 
testing, we have revised these questions to read ``How much do you 
think [drug name] would lower A1C levels for patients with type 2 
diabetes?'' and ``How much do you think [drug name] would help with 
weight loss for patients with type 2 diabetes?'' It is a proper subject 
for FDA research to study whether particular framing of statements 
contributes to an HCP's accurate understanding or to misunderstanding 
about drugs to inform their prescribing decisions in the course of 
their practice of medicine.
    (Comment 23) One comment suggested deleting or clarifying Phase 1 
Question 11 to refer to ``type 1 or type 2 diabetes'' rather than 
``other health conditions.'' This comment also suggested revising Phase 
1 Questions 12 to 16 to indicate they are focused on diabetic patients.
    (Response 23) We have deleted Question 11 and have revised the 
other items to refer specifically to type 2 diabetes to improve 
question clarity.
    (Comment 24) One comment suggested deleting or revising Phase 1 
Question 10 to read ``[Drug X] is approved for helping people without 
diabetes lose weight.''
    (Response 24) We have deleted this question.
    (Comment 25) One comment recommended deleting Phase 1 Questions 17 
to 23 and Questions 35 to 38 because responses could be influenced by 
many reasons and it is unclear how these questions relate to the study 
objectives.
    (Response 25) These items measure perceived efficacy and attitude 
toward the drug. Attitude toward the drug and perceived efficacy can 
influence other outcomes such as the intention to take the drug or 
mention it to the doctor. Thus, we believe it is important to assess 
these variables. Given that we are randomizing participants to 
experimental conditions, we suspect that differences between 
experimental conditions are due to the experimental manipulations 
rather than participants' background and experiences. Additionally, we 
also included several variables to measure participants' experience 
with diabetes and weight loss, as well as medications for these 
conditions. If these variables are related to perceived efficacy and 
attitude toward the drug, we plan to include them as covariates in 
analyses.
    (Comment 26) One comment suggested deleting Phase 1 Questions 32 to 
34 because these questions ask about perceived risks and side effects 
that are not within the stated study objectives.
    (Response 26) The goal of the study is to examine the impact of the 
presence of the comparative claim and type of disclosures; it is 
possible for participants to form different (and potentially distorted) 
risk perceptions based on the presence or absence of the comparative 
claim or type of disclosure. Assessing this outcome will allow us to 
determine whether risk perceptions vary based on exposure to study 
manipulations.
    (Comment 27) One comment suggested deleting or revising Phase 2 
Questions 4 to 11 and Questions 14 to 18 because participants will not 
be able to evaluate the safety and efficacy of, or make decisions 
about, their intended course of action related to the fictitious drug.
    (Response 27) The promotional material will include information on 
primary and secondary endpoints as well as an important safety 
information section. We acknowledge that in a clinical setting patients 
and HCPs may use additional information. However, the intent of these 
items is to understand whether exposure to different types of 
information related to the comparative claim and disclosure results in 
different comprehension or behavioral intention. All participants will 
have the same level of information regarding the fictitious drug with 
the only difference being the manipulated content. So, we would expect 
that all participants will be equally informed about the fictitious 
drug and differences between conditions could be attributed to the 
manipulations. Items 4 to 11 assess participant comprehension of 
promotional material.
    (Comment 28) One comment suggested deleting all Phase 2 questions 
about the advertising statement, questions assessing participants' 
understanding of how prescription drugs and biologic products work, 
familiarity with similar treatments, and attitudes about pharmaceutical 
companies; in particular, Questions 3, 27 to 30, and 36.
    (Response 28) The answers to these questions may help contextualize 
differences between the experimental conditions. There is some evidence 
that prior attitudes toward prescription drugs and pharmaceutical 
companies have an impact on attitudes and perceptions of particular 
prescription drugs and DTC ads (Ref. 13). Question 3 assesses attitudes 
toward the disclosure. For instance, it is possible that participants 
exposed to a certain disclosure may have more favorable attitudes 
towards the drug because they viewed the disclosure as trustworthy. 
Questions 27 to 30 and 36 will also help us contextualize the findings 
by understanding participants' prior beliefs about prescription drugs, 
biosimilars, and pharmaceutical companies that may influence their 
responses and how they process the disclosure, in which case we would 
include them as controls in our analyses.
    (Comment 29) One comment suggested moving Phase 2 Questions 27 to 
38 to the beginning of the questionnaire, before the participant views 
the stimuli.
    (Response 29) These questions are included to contextualize the 
findings and obtain an understanding of participants' prior beliefs and 
perceptions about biosimilars and more broadly prescription drug 
promotion. We ask these questions after the main study outcomes are 
assessed so that we do not contaminate participants' thoughts and 
perceptions of the promotional material. In addition, we do not want to 
prime the participants in the control condition (who are not told the 
drug is a biosimilar) to think the drug is a biosimilar, which would be 
equivalent to one of the other study conditions.
    (Comment 30) One comment suggested adding a response option to 
capture a neutral or ``no reaction'' response to questions.
    (Response 30) There are benefits and drawbacks to including a 
neutral or ``no reaction'' response in survey research, and the 
decision to use a neutral mid-point depends on the goal of the 
measures. For items assessing comprehension of disclosure language, we 
include a ``do not know'' option as this response would indicate some 
level of uncertainty about the meaning of the disclosure, which is 
meaningful and actionable information. However, when assessing 
perceptions and attitudes towards disclosures, our objective is to 
force a selection and have participants choose a leaning towards 
agreement or disagreement with the statement. Inclusion of a neutral 
response option in these instances could potentially encourage 
``satisficing''--cuing participants to select a neutral response under 
uncertainty because it is offered (Ref. 14).
    (Comment 31) One comment suggested clarifying Phase 2 Question 28 
to make clear it refers to the

[[Page 50893]]

approved uses of biosimilars, not health conditions generally.
    (Response 31) We have removed this item from our survey.
    (Comment 32) One comment suggested revising Phase 2 Question 18 to 
ask about safety and efficacy separately because they may introduce 
bias if located in the same items.
    (Response 32) We acknowledge safety and efficacy are separate 
issues, and we assess beliefs about safety and efficacy separately in 
Questions 5 to 8. However, because biosimilars have no clinically 
meaningful differences in safety, purity, or potency (safety and 
effectiveness) from their reference product, we are also interested in 
the impact of the disclosure statement on participants' perceptions of 
safety and efficacy as a whole. Given this, we do not believe this 
question will introduce bias.
    (Comment 33) One comment suggested either deleting or revising 
questions about the biosimilar disclosure to make clear what ``same 
types of sources'' means.
    (Response 33) The wording of the biosimilar disclosure statement 
was crafted using terminology from FDA's Biosimilar Basics Patient 
Materials (https://www.fda.gov/drugs/biosimilars/patient-materials), 
and we tested its meaning during our in-depth cognitive interviews. 
Both the consumer and provider groups sufficiently understood this 
statement.
    (Comment 34) One comment suggested only asking Phase 2 Question 17 
of participants who are currently receiving a biologic.
    (Response 34) The intent of the question is to understand whether 
participants would ask their doctor to switch their medication after 
viewing the ad. We provided a hypothetical scenario and asked 
participants to answer this question as if they were taking the 
reference medication or another prescription medication to treat RA. 
This question would not be feasible among only those with RA who are 
receiving a biologic, given the prevalence of RA in the population 
(i.e., 0.6 percent) as we only expect to have a few individuals 
diagnosed with RA, if any.
    FDA estimates the burden of this collection of information as 
follows:

                                                     Table 2--Estimated Annual Reporting Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                    No. of
                   Activity                         No. of       responses per   Total annual         Average  burden per  response         Total hours
                                                  respondents     respondent       responses
--------------------------------------------------------------------------------------------------------------------------------------------------------
Study 1 Pretest screener (HCPs)...............             278               1             278  0.08 (5 minutes)........................           22.24
Study 1 Pretest screener (consumers)..........             278               1             278  0.08 (5 minutes)........................           22.24
Study 1 Pretest completes (HCPs)..............             139               1             139  0.33 (20 minutes).......................           45.87
Study 1 Pretest completes (consumers).........             139               1             139  0.33 (20 minutes).......................           45.87
Study 2 Pretest screener (HCPs)...............             476               1             476  0.08 (5 minutes)........................           38.08
Study 2 Pretest screener (consumers)..........             476               1             476  0.08 (5 minutes)........................           38.08
Study 2 Pretest completes (HCPs)..............             238               1             238  0.33 (20 minutes).......................           78.54
Study 2 Pretest completes (consumers).........             238               1             238  0.33 (20 minutes).......................           78.54
Study 1 Main study screener (HCPs)............             990               1             990  0.08 (5 minutes)........................            79.2
Study 1 Main study screener (consumers).......             990               1             990  0.08 (5 minutes)........................            79.2
Study 1 Main study completes (HCPs)...........             495               1             495  0.33 (20 minutes).......................          163.35
Study 1 Main study completes (consumers)......             495               1             495  0.33 (20 minutes).......................          163.35
Study 2 Main study screener (HCPs)............             792               1             792  0.08 (5 minutes)........................           63.36
Study 2 Main study screener (consumers).......             792               1             792  0.08 (5 minutes)........................           63.36
Study 2 Main study completes (HCPs)...........             396               1             396  0.33 (20 minutes).......................          130.68
Study 2 Main study completes (consumers)......             396               1             396  0.33 (20 minutes).......................          130.68
                                               ---------------------------------------------------------------------------------------------------------
    Total.....................................           7,608  ..............           7,608  ........................................           1,243
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
Note: With online surveys, several participants may be in the process of completing the survey at the time that the total target sample is reached.
  Those participants will be allowed to complete the survey, which can result in the number of valid completes exceeding the target number. With this in
  mind, we have included an additional 10 percent over our target number of valid completes to account for some overage.

II. References

    The following references marked with an asterisk (*) are on display 
with the Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, 240-
402-7500 and are available for viewing by interested persons between 9 
a.m. and 4 p.m., Monday through Friday; these also are available 
electronically at https://www.regulations.gov. References without 
asterisks are not on public display at https://www.regulations.gov 
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. Andrews, J.C. (2011). ``Warnings and Disclosures.'' In: 
Communicating Risks and Benefits: An Evidence-Based User's Guide. 
Fischhoff, B., N.T. Brewer, and J.S. Downs, (Eds). FDA: Silver 
Spring, MD. pp. 149-161.
2. Russo France, K. and P. Fitzgerald Bone (2005). ``Policy Makers' 
Paradigms and Evidence from Consumer Interpretations of Dietary 
Supplement Labels.'' Journal of Consumer Affairs, 39(1), 27-51.
3. Mason, M.J. and D.L. Scammon (2011). ``Unintended Consequences of 
Health Supplement Information Regulations: The Importance of 
Recognizing Consumer Motivations.'' Journal of Consumer Affairs, 
45(2), 201-223.
4. Betts, K.R., K.J. Aikin, V. Boudewyns, et al. (2017). ``Physician 
Response to Contextualized Price-Comparison Claims in Prescription 
Drug Advertising.'' Journal of Communication in Healthcare, 10(3), 
195-204.
5. Betts, K.R., V. Boudewyns, K.J. Aikin, et al. (2018). ``Serious 
and Actionable Risks, Plus Disclosure: Investigating an Alternative 
Approach for Presenting Risk Information in Prescription Drug 
Television Advertisements.'' Research in Social and Administrative 
Pharmacy, 14(10), 951-963.
6. Sullivan, H.W., A.C. O'Donoghue, K.T. David, et al. (2018). 
``Disclosing Accelerated Approval on 
Direct[hyphen]To[hyphen]Consumer Prescription Drug websites.'' 
Pharmacoepidemiology and Drug Safety, 27(11), 1277-1280.
7. *Kaiser Family Foundation. (2020). Professionally Active 
Specialist

[[Page 50894]]

Physicians by Field. Retrieved from https://www.kff.org/other/state-indicator/physicians-by-specialty-area.
8. Corbin, J.C., V.F. Reyna, R.B. Weldon, et al. (2015). ``How 
Reasoning, Judgment, and Decision Making Are Colored by Gist-Based 
Intuition: A Fuzzy-Trace Theory Approach.'' Journal of Applied 
Research in Memory and Cognition, 4(4), 344-355. https://doi.org/10.1016/j.jarmac.2015.09.001.
9. Bornstein, R.F. (1989). ``Exposure and Affect: Overview and Meta-
Analysis of Research, 1968-1987.'' Psychological Bulletin, 106(2), 
265.
10. Bornstein, R.F. and P.R. D'Agostino (1994). ``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.
11. Friedman, L.M., Furberg, C.D., and D.L. DeMets, Fundamentals of 
Clinical Trials. 1998. Spring Science-Business Media, LLC: New York, 
NY.
12. Fisher, R.A. (1937). The Design of Experiments. Edinburgh, 
United Kingdom: Oliver and Boyd.
13. Hausman, A. (2008). ``Direct-To-Consumer Advertising and Its 
Effect on Prescription Requests.'' Journal of Advertising Research, 
48(1), 42-56.
14. Krosnick, J.A. (2018). ``Questionnaire Design.'' In The Palgrave 
Handbook of Survey Research (pp. 439-455). Palgrave Macmillan, Cham.

    Dated: September 3, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2021-19690 Filed 9-10-21; 8:45 am]
BILLING CODE 4164-01-P