50888 Federal Register / Vol. 86, No. 174 / Monday, September 13, 2021 / Notices 

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, PRAStaff@

fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: In 

compliance with 44 U.S.C. 3507, FDA 

has submitted the following proposed 

collection of information to OMB for 

review and clearance. 

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/officeofmedicalproducts

andtobacco/cder/ucm090276.htm. The 

website includes links to the latest 

Federal Register notices and peerreviewed 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 nonmisleading 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 


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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 × 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] 

Comparative secondary 

claim 

Secondary claim disclosure 

‘‘Drug X is not a treatment 

for [claim]’’ 

‘‘In a clinical trial, 

participants [quantitative 

information] on Drug X’’ 

‘‘Drug X is not a treatment 

for [claim]’’ AND 

‘‘In a clinical trial, 

participants [quantitative 

information] on Drug X’’ 

None 

(no secondary claim disclosure) 

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-toconsumer; 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. 


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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. 


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(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 


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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 midpoint 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 


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Federal Register / Vol. 86, No. 174 / Monday, September 13, 2021 / Notices 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

Activity No. of 

respondents 

No. of 

responses 

per 

respondent 

Total annual 

responses 

Average 

burden per 

response 

Total hours 

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 

1There 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-To-Consumer Prescription Drug 

websites.’’ Pharmacoepidemiology and 

Drug Safety, 27(11), 1277–1280. 

7. *Kaiser Family Foundation. (2020). 

Professionally Active Specialist 


lotter on DSK11XQN23PROD with NOTICES1
50894 Federal Register / Vol. 86, No. 174 / Monday, September 13, 2021 / Notices 

Physicians by Field. Retrieved from 

https://www.kff.org/other/stateindicator/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-ToConsumer 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 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Health Resources and Services 

Administration 

Opportunity for Comments on 

Proposed Updates to the Bright 

Futures Periodicity Schedule as Part of 

the HRSA-Supported Preventive 

Services Guidelines for Infants, 

Children, and Adolescents 

AGENCY: Health Resources and Services 

Administration (HRSA), Department of 

Health and Human Services. 

ACTION: Notice. 

SUMMARY: This notice seeks public 

comment on several proposed updates 

to The Periodicity Schedule of the 

Bright Futures Recommendations for 

Pediatric Preventive Health Care 

(‘‘Bright Futures Periodicity Schedule’’), 

as part of the HRSA-supported 

preventive service guidelines for 

infants, children, and adolescents. 

Please see https://mchb.hrsa.gov/ 

maternal-child-health-topics/childhealth/bright-futures.html for additional 

information. The Periodicity Schedule 

is maintained in part through a national 

cooperative agreement, the Bright 

Futures Pediatric Implementation 

Program. If accepted by HRSA, a 

proposed update to the Bright Futures 

Periodicity Schedule will provide 

additional clinical guidance to 

providers and, under the Public Health 

Service Act, would require certain 

insurance plans and issuers to provide 

coverage without cost-sharing of such 

updated preventive care and screenings. 

DATES: Members of the public are 

invited to provide written comments no 

later than October 13, 2021. All 

comments received on or before this 

date will be reviewed and considered by 

the Bright Futures Periodicity Schedule 

Workgroup and provided for further 

consideration by HRSA in determining 

the recommended updates that it will 

support. 

ADDRESSES: Members of the public who 

wish to provide comments can do so by 

accessing the public comment web page 

at: https://mchb.hrsa.gov/maternalchild-health-topics/child-health/brightfutures.html. 

FOR FURTHER INFORMATION CONTACT: 

Savannah Kidd, HRSA, Maternal and 

Child Health Bureau, email: SKidd@

hrsa.gov, telephone: (301) 287–2601. 

SUPPLEMENTARY INFORMATION: The 

Periodicity Schedule of the Bright 

Futures Recommendations for Pediatric 

Preventive Health Care (‘‘Bright Futures 

Periodicity Schedule’’), as part of the 

HRSA-supported preventive service 

guidelines for infants, children, and 

adolescents, is maintained in part 

through a national cooperative 

agreement, the Bright Futures Pediatric 

Implementation Program. Under Section 

2713 of the Public Health Service Act, 

non-grandfathered group health plans 

and health insurance issuers must 

include coverage, without cost sharing, 

for certain preventive services for plan 

years (in the individual market, policy 

years) that begin on or after the date that 

is 1-year after the date the 

recommendation or guideline is issued. 

These include preventive health 

services provided for in the Bright 

Futures Periodicity Schedule as part of 

the HRSA-supported preventive services 

guidelines for infants, children, and 

adolescents. A panel of pediatric 

primary care experts convened to 

review the latest evidence has identified 

proposed updates to the Bright Futures 

Periodicity Schedule in several areas in 

response to new evidence impacting 

children. The proposed updates to the 

Bright Futures Periodicity Schedule are: 

(1) A new category for sudden cardiac 

arrest and sudden cardiac death risk 

assessment, (2) a new category for 

hepatitis B virus infection risk 

assessment, (3) add suicide risk as an 

element of universal screening for 

children ages 12–21, and (4) update of 

Psychosocial/Behavioral Assessment to 

Behavioral/Social/Emotional Screening. 

The updated category title will be 

‘‘Behavioral/Social/Emotional 

Screening’’ with no revision to the ages 

in which the screening occurs (newborn 

to 21 years). Finally, two references 

related to dental fluoride varnish and 

fluoride supplementation are proposed 

to be added with no recommended 

changes to clinical practice. 

The American Academy of Pediatrics, 

which has been the HRSA cooperative 

agreement recipient for this program 

since 2007, maintains the Periodicity 

Schedule. Under HRSA’s cooperative 

agreement with the American Academy 

of Pediatrics, the Bright Futures 

Program is required to administer a 

process for developing and regularly 

recommending, as needed, updates to 

the Bright Futures Periodicity Schedule. 

As described in the Notice of Funding 

Opportunity for the Bright Futures 

Program (HRSA–18–078), the 

consideration of potential updates is 

expected to be ‘‘a comprehensive, 

objective, and transparent review of 

available evidence that incorporates 

opportunity for public comment. 

Accordingly, the award recipient will 

review the evidence on an annual basis 

to determine whether updates are 

needed, using a deliberative review 

process by experts qualified to conduct 

such a review; administer the receipt 

and consideration of public comments 

for a minimum of 30 calendar days 

following publication of the Federal 

Register Notice setting forth the 

proposed updates; and provide to HRSA 

a written report that sets forth its 

recommended updates, including a 

summary of the public comments it 

received, a list of general topics that 

were commented on and its responses to 

those comments.’’ 

Authority: 2713(a)(3) of the Public 

Health Service Act, 42 U.S.C. 300gg– 

13(a)(3). 

Diana Espinosa, 

Acting Administrator. 

[FR Doc. 2021–19630 Filed 9–10–21; 8:45 am] 

BILLING CODE 4165–15–P 


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