[Federal Register Volume 87, Number 57 (Thursday, March 24, 2022)]
[Notices]
[Pages 16743-16748]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-06220]


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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2021-N-0371]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Accelerated Approval 
Disclosures on Direct-to-Consumer Prescription Drug Websites

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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

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

DATES: Submit written comments (including recommendations) on the 
collection of information by April 25, 2022.

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 ``Accelerated Approval Disclosures on Direct-
to-Consumer Prescription Drug Websites.'' Also include the FDA docket 
number found in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: Ila S. Mizrachi, Office of Operations, 
Food and Drug Administration, Three White Flint North, 10A-12M, 11601 
Landsdown St., North Bethesda, MD 20852, 301-796-7726, 
<a href="/cdn-cgi/l/email-protection#46161407153227202006202227682e2e3568212930"><span class="__cf_email__" data-cfemail="4a1a180b193e2b2c2c0a2c2e2b64222239642d253c">[email protected]</span></a>.

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

Accelerated Approval Disclosures on Direct-to-Consumer Prescription 
Drug Websites

OMB Control Number 0910-NEW

    Section 1701(a)(4) of the Public Health Service Act (PHS 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, focusing in particular on three main topic 
areas: Advertising features, including content and format; target 
populations; and research quality. Through the evaluation of 
advertising features, we assess how elements such as graphics, format, 
and disease and product characteristics impact the communication and 
understanding of prescription drug risks and benefits. Focusing on 
target populations allows us to evaluate how understanding of 
prescription drug risks and benefits may vary as a function of 
audience, and our focus on research quality aims at maximizing the 
quality of our research data through analytical methodology development 
and investigation of sampling and response issues. This study will 
inform the first topic area, advertising features, including content 
and format; and the second topic area, target populations.
    Because we recognize the strength of data and the confidence in the 
robust nature of the findings is improved through the results of 
multiple converging studies, we continue to develop evidence to inform 
our thinking. We evaluate the results from our studies within the 
broader context of research and findings from other sources, and this 
larger body of knowledge collectively informs our policies as well as 
our research program. Our research is documented on our homepage, which 
can be found at: https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/office-prescription-drug-promotion-opdp-research. 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 direct-to-
consumer (DTC) survey conducted in 1999.

I. Background

    Pursuant to section 506(c) of the FD&C Act (21 U.S.C. 356(c)) and 
21 CFR part 314, subpart H (or 21 CFR part 601, subpart E for 
biological products), FDA may grant accelerated approval to a drug 
product under section 505(c) of the FD&C Act (21 U.S.C. 355(c)) or a 
biological product under section 351(a) of the PHS Act (42 U.S.C. 
262(a)). This pathway enables faster approval of prescription drugs 
intended to treat serious or life-threatening illnesses. Accelerated 
approval may be based on a determination that a drug product has an 
effect on a surrogate endpoint (for example, a blood test result) that 
is reasonably likely to predict clinical benefit, or on a clinical 
endpoint that can be measured earlier than irreversible morbidity or 
mortality, that is reasonably likely to predict an effect on 
irreversible morbidity or mortality or other clinical benefit (i.e., an 
intermediate clinical endpoint). In approving a drug under the 
accelerated

[[Page 16744]]

approval pathway, the severity, rarity, or prevalence of a condition, 
and the availability or lack of alternative treatments, are taken into 
account.
    The accelerated approval pathway is limited to certain products 
intended to treat serious or life-threatening illnesses as there can be 
``[u]ncertainty about whether clinical benefit will be verified and the 
possibility of undiscovered risks'' (FDA's 2014 guidance for industry 
entitled ``Expedited Programs for Serious Conditions--Drugs and 
Biologics,'' available at https://www.fda.gov/downloads/Drugs/Guidances/UCM358301.pdf). Sponsors are generally required to conduct 
post-approval studies to verify and describe the predicted clinical 
benefit, but those confirmatory studies are not complete at the time 
that the accelerated approval is granted (Ref. 1). In the event that 
the required post-approval confirmatory studies fail to verify and 
describe the predicted effect or clinical benefit, a drug's approval 
can be withdrawn using expedited procedures.
    Under FDA regulations governing physician labeling for prescription 
drugs, the INDICATIONS AND USAGE section of FDA-approved prescribing 
information for a drug approved under accelerated approval must include 
not only the indication (Sec.  201.57(c) (21 CFR 201.57(c))) but also a 
``succinct description of the limitations of usefulness of the drug and 
any uncertainty about anticipated clinical benefits . . .'' (Sec.  
201.57(c)(2)(i)(B)). In a guidance, FDA recommended that in addition to 
these required elements, the INDICATIONS AND USAGE section for drugs 
approved under accelerated approval should generally acknowledge that 
continued approval for the drug or indication may be contingent on 
verification and description of clinical benefit in confirmatory trials 
(FDA 2019 guidance for industry entitled ``Labeling for Human 
Prescription Drug and Biological Products Approved Under the 
Accelerated Approval Regulatory Pathway,'' available at https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM390058.pdf).
    Some DTC websites have included disclosures about accelerated 
approval, and of those, many included similar content to that seen in 
the INDICATIONS AND USAGE section of approved labeling. A content 
analysis of DTC websites for accelerated approval products found that 
21 percent of the disclosures used language directly from the approved 
physician labeling, 79 percent of the disclosures used at least some 
medical language, but 27 percent of the websites did not include any 
disclosure that the products attained approval through this pathway 
(Ref. 2). The same analysis found that 84 percent of accelerated 
approval disclosures on DTC websites mentioned the approval basis, 68 
percent mentioned unknown outcomes, and 47 percent mentioned 
confirmatory trials (Ref. 2).
    OPDP recently conducted a general-population study testing the 
disclosure of FDA accelerated approval information on a DTC 
prescription drug website (OMB control number 0910-0872--Experimental 
Study of an Accelerated Approval Disclosure; the 0910-0872 Study). The 
study tested a control condition with no disclosure; a disclosure based 
on wording used in physician labeling, including more complex or 
technical terminology (physician-labeling disclosure); and a consumer-
friendly disclosure drafted using simpler language intended to be 
suited for that audience (consumer-friendly disclosure). The 
disclosures had three elements: (1) Approval basis, (2) unknown 
outcomes, and (3) confirmatory trials. The physician labeling 
disclosure was ``This indication is based on response rate. An 
improvement in survival or disease-related symptoms has not been 
established. Continued approval for this indication may be contingent 
upon verification of clinical benefit in subsequent trials.'' The 
consumer-friendly disclosure was ``In a clinical trial, [Drug X] 
returned blood counts to normal. However, we currently do not know if 
[Drug X] helps people live longer or feel better. We continue to study 
[Drug X] in clinical trials to learn more about [Drug X]'s benefits.'' 
We also varied whether the physician-labeling and consumer-friendly 
disclosures were presented with low or high prominence (varying the 
size, color, and location of the disclosure). Preliminary results 
related to the comprehension of the disclosures tested in that study 
suggest that the consumer-friendly disclosure helped participants 
understand information related to the drug's accelerated approval, but 
that participants' understanding was low overall.

II. New Proposed Study

    The purpose of the current project is to replicate and extend our 
prior research through two studies by: (1) Testing the same 
experimental conditions with a different study population (cancer 
survivors and cancer caregivers in study 1) and, (2) testing additional 
consumer-friendly disclosures in study 2. Replication is an important 
part of science and, if confirmation of prior results is seen, can 
increase confidence in the results from our first study.
    With regard to proposed study 1, public comments for FDA's previous 
accelerated approval disclosure study and other similar FDA studies 
have suggested conducting studies with people who have been diagnosed 
with the medical condition or who are caregivers to patients diagnosed 
with the medical condition that the fictitious drug in the study is 
intended to treat. Specifically, public comments on the previous study 
suggested enrolling participants who have been diagnosed with cancer 
(i.e., cancer survivors) or people who have cared for loved ones with 
cancer (i.e., cancer caregivers). Because a number of oncology products 
are granted accelerated approval, cancer survivors and cancer 
caregivers are more likely to seek out or be exposed to promotion for 
accelerated approval products than the general population. They may 
also be more familiar with cancer-related terms and concepts than the 
general population. Study 1 will involve cancer survivors and cancer 
caregivers, a different population than our prior study. It will test 
the ``three element'' version of the disclosure as noted above. We will 
also test the prominence of the disclosure (see table 1).
    With regard to study 2, public comments on the original study 
(Docket No. FDA-2018-N-3138) expressed concern that over-disclosure 
could dissuade consumers from considering accelerated approval 
products. One public comment specifically suggested removing the 
``unknown outcomes'' element in the consumer-friendly and physician-
labeling disclosures. Based on these comments, in study 2, we propose 
testing four versions of the consumer-friendly disclosure (table 2): 
The ``three element'' version of the consumer-friendly disclosure as 
well as three other consumer-friendly disclosures that vary with 
respect to which of these three elements they address. This will allow 
us to evaluate the impact on participants' comprehension of the 
disclosure and perception of the fictitious drug when they view a 
disclosure with only the approval basis, the approval basis plus 
information about the unknown outcomes, the approval basis plus 
information about confirmatory trials, and finally the approval basis 
plus information about both the unknown outcomes and confirmatory 
trials. In study 2, the prominence of all the test conditions will be 
the same and will be the same as the ``high prominence'' version tested 
in study 1.

[[Page 16745]]

    We plan to conduct two pretests not longer than 20 minutes, 
administered via internet panel, to pilot the main study procedures. We 
then plan to conduct two main studies not longer than 20 minutes, 
administered via internet panel. For the pretests and main studies, we 
will randomly assign the participants to one of the test conditions 
(see table 1 for the study 1 design and table 2 for the study 2 
design). In both studies, participants will view a website for a 
fictitious oncology prescription drug. After viewing the website, 
participants will complete a questionnaire that assesses whether 
participants noticed the disclosure and their understanding of it, as 
well as perceptions of the drug's risks and benefits. We will also 
measure covariates such as demographics and literacy. The questionnaire 
is available upon request from <a href="/cdn-cgi/l/email-protection#e1a5b5a29384928480938289a1878580cf898992cf868e97"><span class="__cf_email__" data-cfemail="ace8f8efdec9dfc9cddecfc4eccac8cd82c4c4df82cbc3da">[email protected]</span></a>.
    For study 1, we hypothesize that participants will be more likely 
to notice the disclosure when it is presented more, rather than less, 
prominently. In turn, we expect that participants' perceptions of the 
drug are more likely to be affected by the disclosure in the high 
prominence condition. We also hypothesize that participants will be 
more likely to notice and understand the disclosure and use it to form 
their perceptions of the drug if they view the consumer-friendly 
language. For study 2, we hypothesize that participants will be more 
likely to understand each accelerated approval concept (i.e., 
confirmatory trials, unknown outcomes) when the disclosure directly 
addresses the concept, compared with when the disclosure does not 
directly address the concept. Finally, we will explore whether the 
inclusion of the concepts of confirmatory trials and unknown outcomes 
in the disclosure affects participants' perceived risk, perceived risk-
benefit tradeoff, perceptions of the website, or information-seeking 
intentions. To test these hypotheses, we will conduct inferential 
statistical tests such as logistic regression and analysis of variance.
    For the pretests and main studies, we plan to recruit individuals 
who report a diagnosis with any cancer (except for certain non-melanoma 
skin cancers) for half the sample and individuals who report being a 
caregiver for someone with a diagnosis with any cancer (except for 
certain non-melanoma skin cancers) for the other half of the sample. We 
will exclude individuals who work for the U.S. Department of Health and 
Human Services or work in the healthcare, marketing, advertising, or 
pharmaceutical industries. With the sample sizes described below, we 
will have sufficient power to detect small-sized effects in the main 
study (table 3).

                                             Table 1--Study 1 Design
----------------------------------------------------------------------------------------------------------------
                                           High prominence           Low prominence               Absent
----------------------------------------------------------------------------------------------------------------
Physician-labeling version...........  Condition 1............  Condition 3............  Condition 5.
Consumer-friendly version............  Condition 2............  Condition 4............
----------------------------------------------------------------------------------------------------------------


                                             Table 2--Study 2 Design
                                     [Consumer-friendly disclosure elements]
----------------------------------------------------------------------------------------------------------------
                                                                                               Approval basis +
                                                       Approval basis +    Approval basis +   unknown outcomes +
                                    Approval basis     unknown outcomes      confirmatory        confirmatory
                                                                                trials              trials
----------------------------------------------------------------------------------------------------------------
High prominence.................  Condition 6.......  Condition 7.......  Condition 8.......  Study 1 Condition
                                                                                               2.
----------------------------------------------------------------------------------------------------------------

    In the Federal Register of June 11, 2021 (86 FR 31323), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. FDA received one submission that was PRA-
related. Within the submission, 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 the commenter that the entirety of their 
comments was considered even if not fully captured by our paraphrasing 
in this document. The following acronyms are used here: DTC = direct-
to-consumer; HCP = healthcare professional; FDA and the Agency = Food 
and Drug Administration; OPDP = FDA's Office of Prescription Drug 
Promotion.
    (Comment 1) Comment 1 expressed concern that this research will 
duplicate a prior FDA study and lack practical utility. The comment 
asserts that while the 60-day PRA notice provided a statement of 
``preliminary results'' of the prior study, full study materials, 
results, and conclusions of that prior study have not been published. 
It requested that the results of the prior study be published before 
this study is conducted, suggesting that, without publishing the 
results of the prior study, FDA has not addressed how the new proposed 
research would address open research issues or limitations of the prior 
study.
    (Response 1) Contrary to the comment's suggestion, we do not plan 
to duplicate the prior research, although there often is value in that 
undertaking. Rather, the present research seeks to replicate the 
previous study in a new patient population and extend the previous 
study by testing additional versions of the disclosure. The new 
research is directly informed by open research issues and limitations 
raised in the public comments from the previous study. The proposed 
studies will be conducted in a new cancer survivor and caregiver 
sample, which differs from the sample in the prior study, which was 
conducted with a general population sample. As noted above, cancer 
survivors and cancer caregivers are more likely to seek out or be 
exposed to promotion for accelerated approval products than the general 
population. They may also be more familiar with cancer-related terms 
and concepts than the general population. Replications in different 
study samples are often proposed. Indeed, at the time of the previously 
proposed study (0910-0872 Study), public comments suggested conducting 
the study with cancer survivors who had used oncology products. Also, 
in response to public comments on the prior study design, we will 
extend the prior research by testing additional versions of the 
disclosure. This study therefore has practical utility to expand our 
information regarding website disclosures regarding accelerated 
approval drugs, both by extending to additional versions of the

[[Page 16746]]

disclosure related to our overall questions, and to determine if 
results are consistent with those of the earlier study. We intend to 
publish the results of the current study as well as the prior study.
    (Comment 2) Comment 2 stated that establishing mandates to unduly 
emphasize a product's accelerated approval status could deter 
appropriate usage and lead to misconception and confusion among 
patients. The comment specifically referred to one statement in the 
disclosure, ``we currently do not know if [Drug X] helps people live 
longer or feel better'' to suggest that the disclosure may oversimplify 
the benefits of the product and thus discourage patients from getting 
needed treatments. The comment later stated that the availability of 
FDA prior review of promotional pieces for accelerated approval means 
there is less need to prescribe specific overarching new rules for 
disclosures because FDA can consider disclosures on a case-by-case 
basis.
    (Response 2) This notice proposes a data collection for research 
purposes and does not establish a mandate or propose a new rule. 
Instead, it proposes research that may inform FDA and stakeholder 
thinking on accelerated approval product disclosures in DTC promotional 
materials. The research will specifically investigate patient 
understanding of and reaction to the disclosure language about a 
product's accelerated approval status. Study 2 was designed in direct 
response to public comment on the previously proposed study (0910-0872 
Study) raising concerns about over-disclosure. Study 2 will test 
several conditions based on disclosures found in the marketplace, two 
of which will not include the statement ``we currently do not know if 
[Drug X] helps people live longer or feel better'' (see table 2).
    (Comment 3) Comment 3 suggested that DTC promotional materials are 
not the best venue for providing information about prescription drugs, 
given the role of healthcare professionals (HCPs) in discussing and 
prescribing treatments. Based on this, the comment suggested modifying 
the study to focus on prescriber-patient interactions rather than DTC 
promotion by including a component to evaluate patient understanding of 
accelerated approval after consultation with a prescriber.
    (Response 3) We agree that the prescriber-patient interaction is 
important. Consumers often wish to participate in shared decision-
making with HCPs when selecting prescription drugs and may request 
specific prescription drugs from their HCPs based on promotions they 
have seen in the marketplace. Because information consumers receive 
through DTC prescription drug promotion can impact these requests, it 
is important to investigate how the information in prescription drug 
promotional pieces impacts consumer attention, understanding, and 
perceptions.
    (Comment 4) Comment 4 suggested conducting qualitative interviews 
or a blended approach of qualitative and quantitative research rather 
than a quantitative study. In addition, the comment recommended that 
the interviews include showing the stimuli to participants, asking them 
questions about the stimuli, and then showing them the stimuli again so 
they can read the disclosure and have it in front of them while 
answering questions.
    (Response 4) We plan to conduct nine 1-hour interviews to 
cognitively test the stimuli and questionnaire. These interviews will 
allow for indepth discussions with participants, and the findings from 
the interviews will help improve the study materials. In addition, the 
questionnaire follows the approach the commenter suggested: 
Participants view the stimuli and answer questions, then see the 
disclosure again for questions 16 and 17. This will allow us to test 
what participants remember and understand after visiting a website for 
an accelerated approval product, as well as their understanding of the 
disclosure language while it is in front of them. We will use the 
cognitive interviews and pretesting to determine whether participants 
will be able to view the stimuli when answering more of the questions 
in study 2.
    (Comment 5) Comment 5 suggested screening for patients who have a 
personal experience with Acute Lymphoblastic Leukemia (ALL) (the cancer 
referred to in the study stimuli) and who have received accelerated 
approval products from their prescribers.
    (Response 5) We will ask participants about the type of cancer and 
type of treatment(s) they or their loved one had. In this study, we 
will not ask if they used an accelerated approval product, because 
participants are unlikely to know this information. In the pretest, we 
will examine the feasibility of quotas aiming for a broad range of 
cancer diagnoses in the sample, including blood cancers like ALL. We 
will also use the pretest to examine the feasibility of restricting 
recruitment to cancer survivors, and caregivers for cancer survivors, 
who have received a systemic therapy (e.g., chemotherapy, hormonal 
therapy, immune therapy, targeted therapy).
    (Comment 6) Comment 6 questioned why caregivers are included in the 
sample and noted that it is unclear what direct role caregivers have in 
drug prescribing decisions.
    (Response 6) We included caregivers in part because previous public 
comments have encouraged FDA to include caregivers in DTC research (for 
example, Docket No. FDA-2019-N-2313). Prior research also supports the 
inclusion of caregivers in a study on consumer understanding of health 
information on a DTC prescription drug website. Surveys have found that 
many people searching for health information online are doing so on 
behalf of someone else (e.g., Refs. 3 and 4). These ``surrogate 
seekers'' are more likely to be caregivers (Ref. 5). In addition, 
caregivers are a known audience for DTC prescription drug websites. For 
instance, to enter some DTC prescription drug websites, people must 
select whether they are ``a patient or caregiver'' or a ``healthcare 
provider.'' Other DTC prescription drug websites specifically include 
information for caregivers.
    (Comment 7) Comment 7 stated that information on the proposed 
number of study participants was not observed in the 60-day notice, and 
suggested a minimum of 200-300 participants, with 400-500 being 
optimal. The comment also suggested considering quotas for demographic 
variables such as age and education to allow for subgroup analyses.
    (Response 7) The proposed number of participants can be found in 
table 3 of this notice. Specifically, we propose 630 participants in 
study 1 and 400 participants in study 2. We have not proposed any 
planned subgroup analyses; however, we will have quotas for age, sex, 
race, and education to ensure a diverse sample.
    (Comment 8) Comment 8 suggested that, for study participants to 
understand the disclosures being tested, they must first be told that 
the drug received an accelerated approval; accelerated approval is 
based on an FDA determination that the drug is likely to provide 
meaningful therapeutic benefits to patients over existing treatments 
and likely addresses a significant unmet medical need; and the drug is 
approved based on adequate and well-controlled clinical trial(s) on 
surrogate or intermediate clinical endpoints that are reasonably likely 
to predict clinical benefit, but that the drug's effects need to be 
verified with additional data.
    (Response 8) Consumers encountering DTC websites for accelerated 
approval

[[Page 16747]]

products would not have this background information, so giving this 
information to participants would defeat the purpose of testing what 
perceptions these consumers form from the website disclosures.
    (Comment 9) Comment 9 suggested testing an alternative disclosure 
that would include background information about accelerated approval, 
described in the last comment, along with the disclosures currently 
proposed to be tested.
    (Response 9) We acknowledge that we cannot test all possible 
disclosure language. We based the disclosures we plan to test on FDA-
approved labeling for accelerated approval products and on disclosures 
found in the marketplace (Ref. 2). We encourage research on alternate 
disclosures.
    (Comment 10) Comment 10 stated that question 9, which asks 
participants about their understanding of the confirmatory trials 
concept from the disclosure, is unclear and suggested deleting the 
question or refining the answer options.
    (Response 10) We will delete this question in study 1. As noted in 
the questionnaire, we plan to test two versions of question 9 in the 
study 2 pretests. We will refine or delete this question in study 2 
based on findings from the cognitive interviews and pretesting.
    (Comment 11) Comment 11 suggested clarifying ``quality of life'' in 
consumer-friendly terms and defining specific quality of life measures 
in question 10.
    (Response 11) Question 10 does not refer to a specific quality of 
life measure. In a recent survey of metastatic breast cancer patients, 
most participants (89 percent) reported understanding the term 
``quality of life'' (Ref. 6). We expect participants in this study will 
also understand the term ``quality of life'' without further 
clarification, but we will cognitively test and pretest the question to 
determine if any clarification is needed.
    (Comment 12) Comment 12 stated that questions 11 and 12, which ask 
about risk-benefit tradeoffs, are redundant and too general, not 
sufficient to study over-disclosure, and that these questions typically 
require consumers and HCPs to arrive at the answer together. The 
comment suggested that instead, the study ask whether, based on 
information on the website, participants intend to ask to take the 
drug, not ask to take the drug, speak with a doctor about whether the 
drug is right for them, or none of these.
    (Response 12) We disagree that consumers do not form their own 
perceptions about risk-benefits tradeoffs after seeing DTC promotional 
materials and prior to any discussion with a HCP. Thus, we plan to ask 
participants about their perceptions of the risk-benefit tradeoff 
through question 11, which is a common and validated item in DTC 
research. We will delete question 12 to reduce redundancy (Ref. 7). We 
will also ask about behavioral intentions. Participants do not 
necessarily have the type of cancer the fictitious drug is indicated to 
treat; therefore, it would not make sense to ask them about their 
intentions to ask about the drug for themselves. Instead, similar to 
what the comment requests, question 14 asks whether participants would 
recommend that a loved one diagnosed with the cancer that the 
fictitious drug is indicated to treat ask a doctor about taking the 
drug.
    (Comment 13) Comment 13 recommended deleting question 13, which 
asks about the drug side effects, because it is too general and does 
not test the disclosure.
    (Response 13) Question 13 is intended to measure the effect of the 
disclosure on participants' risk perceptions. We will assess this 
question in cognitive interviews and pretesting and will refine it if 
needed.
    (Comment 14) Comment 14 suggested deleting or refining question 14, 
which asks participants to select all actions they would suggest a 
loved one take (i.e., asking a doctor about taking the drug, asking 
about the drug's risks, its benefits, and its FDA approval). The 
comment stated that because all options may be applicable, it is 
unclear how the item would yield meaningful data for this research.
    (Response 14) We revised question 14 from ``select all that apply'' 
to separate ``yes/no'' items for each action. We will assess the 
utility of asking about each of these actions in cognitive interviews 
and pretesting. At a minimum, we will retain the ``taking [Drug X]'' 
item to assess intentions as discussed in a previous comment.
    (Comment 15) Comment 15 suggested that participants are unlikely to 
have the information to provide yes or no answers to question 19, which 
asks participants whether they used any accelerated approval products 
for their own cancer, and questioned why it is important for a patient 
to understand the regulatory approval pathway for a drug, as opposed to 
information about the drug's safety and effectiveness for use in 
discussion with an HCP.
    (Response 15) We agree that participants are unlikely to know 
whether the product they used was an accelerated approval product and 
will delete this question in this study.
    (Comment 16) Comment 16 suggested deleting question 21, which asks 
how similar the study website was to other DTC websites the participant 
has seen, because it seems vague and not directly related to the 
research question.
    (Response 16) Question 21 is for pretesting purposes only and is 
intended to assess the quality of the stimuli. We will keep question 21 
for pretesting but will not ask it in the main studies.
    FDA estimates the burden of this collection of information as 
follows:

                                                     Table 3--Estimated Annual Reporting Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                 Number of
                  Activity                       Number of     responses per   Total annual           Average burden per response           Total hours
                                                respondents     respondent       responses
--------------------------------------------------------------------------------------------------------------------------------------------------------
Pretest 1 and 2 screener....................           3,600               1           3,600  0.08 (5 minutes)..........................             288
Study 1 and 2 screener......................          20,600               1          20,600  0.08 (5 minutes)..........................           1,648
Pretest 1...................................             100               1             100  0.33 (20 minutes).........................              33
Main Study 1................................             630               1             630  0.33 (20 minutes).........................             208
Pretest 2...................................              80               1              80  0.33 (20 minutes).........................              26
Main Study 2................................             400               1             400  0.33 (20 minutes).........................             132
                                             -----------------------------------------------------------------------------------------------------------
    Total...................................  ..............  ..............  ..............  ..........................................           2,335
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.


[[Page 16748]]

III. References

    The following references marked with an asterisk (*) are on display 
at 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; they 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. Beaver J.A., L.J. Howie, L. Pelosof, et al., ``A 25-Year 
Experience of U.S. Food and Drug Administration Accelerated Approval 
of Malignant Hematology and Oncology Drugs and Biologics: A 
Review.'' JAMA Oncology. 2018; 4(6):849-856.
2. Sullivan H.W., A.C. O'Donoghue, K.T. David, et al., ``Disclosing 
Accelerated Approval on Direct-to-Consumer Prescription Drug 
websites.'' Pharmacoepidemiology and Drug Safety. 2018;27:1277-1280. 
https://doi.org/10.1002/pds.4664.
3. Cutrona, S.L., K.M. Mazor, S.N. Vieux, et al., ``Health 
Information-Seeking on Behalf of Others: Characteristics of 
`Surrogate Seekers'.'' Journal of Cancer Education. 2015;30:12-19. 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4282983/.
4. Sadasivam, R.S., R.L. Kinney, S.C. Lemon, et al., ``Internet 
Health Information Seeking Is a Team Sport: Analysis of the Pew 
Internet Survey.'' International Journal of Medical Informatics. 
2013;82:193-200.
* 5. Bangerter, L.R., J. Griffin, K. Harden, et al., ``Health 
Information-Seeking Behaviors of Family Caregivers: Analysis of the 
Health Information National Trends Survey.'' JMIR Aging. 
2019;2:e11237. https://aging.jmir.org/2019/1/e11237/.
6. von Itzstein, M.S., E. Railey, M.L. Smith, et al., ``Patient 
Familiarity with, Understanding of, and Preferences for Clinical 
Trial Endpoints and Terminology.'' Cancer. 2021;126:1605-1613.
7. Kelly, B.J., D.J. Rupert, K.J. Aikin, et al., ``Development and 
Validation of Prescription Drug Risk, Efficacy, and Benefit 
Perception Measures in the Context of Direct-to-Consumer 
Prescription Drug Advertising.'' Research in Social and 
Administrative Pharmacy. 2021;17:942-955.

    Dated: March 17, 2022.
Andi Lipstein Fristedt,
Deputy Commissioner for Policy, Legislation, and International Affairs, 
U.S. Food and Drug Administration.
[FR Doc. 2022-06220 Filed 3-23-22; 8:45 am]
BILLING CODE 4164-01-P


</pre><script data-cfasync="false" src="/cdn-cgi/scripts/5c5dd728/cloudflare-static/email-decode.min.js"></script></body>
</html>