Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment Request; Accelerated Approval Disclosures on Direct-to-Consumer Prescription Drug Websites, 16743-16748 [2022-06220]
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Federal Register / Vol. 87, No. 57 / Thursday, March 24, 2022 / Notices
On November 22, 2021, Secura Bio,
Inc. submitted a letter asking FDA to
withdraw approval of NDA 205353 for
FARYDAK (panobinostat) Capsules, 10
mg, 15 mg, and 20 mg, pursuant to
§ 314.150(d) (21 CFR 314.150(d)) and
waiving its opportunity for a hearing. In
the letter, Secura Bio, Inc. stated they
are requesting withdrawal of approval of
the NDA for FARYDAK because it was
not feasible for them to complete the
required postmarketing clinical trials.
On November 26, 2021, FDA
acknowledged Secura Bio, Inc.’s request
for withdrawal of approval of the NDA
and waiver of its opportunity for
hearing. FDA also cancelled the ODAC
meeting scheduled for December 2,
2021, since the applicant’s withdrawal
request made discussion at an advisory
committee meeting moot.
For the reasons discussed above, and
in accordance with the applicant’s
request, approval of NDA 205353 for
FARYDAK (panobinostat) Capsules, 10
mg, 15 mg, and 20 mg, and all
amendments and supplements thereto,
is withdrawn under § 314.150(d).
Distribution of FARYDAK
(panobinostat) Capsules, 10 mg, 15 mg,
and 20 mg, into interstate commerce
without an approved application is
illegal and subject to regulatory action
(see sections 505(a) and 301(d) of the
Federal Food, Drug, and Cosmetic Act
(21 U.S.C. 355(a) and 331(d)).
DATES:
Dated: March 18, 2022.
Andi Lipstein Fristedt,
Deputy Commissioner for Policy, Legislation,
and International Affairs, U.S. Food and Drug
Administration.
OMB Control Number 0910–NEW
[FR Doc. 2022–06182 Filed 3–23–22; 8:45 am]
BILLING CODE 4164–01–P
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-toConsumer Prescription Drug Websites
AGENCY:
Food and Drug Administration,
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HHS.
ACTION:
Notice.
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.
SUMMARY:
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Submit written comments
(including recommendations) on the
collection of information by April 25,
2022.
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, PRAStaff@
fda.hhs.gov.
ADDRESSES:
In
compliance with 44 U.S.C. 3507, FDA
has submitted the following proposed
collection of information to OMB for
review and clearance.
SUPPLEMENTARY INFORMATION:
Accelerated Approval Disclosures on
Direct-to-Consumer Prescription Drug
Websites
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
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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/centerdrug-evaluation-and-research-cder/
office-prescription-drug-promotionopdp-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 directto-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
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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 postapproval 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 (§ 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 . . .’’ (§ 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/
GuidanceComplianceRegulatory
Information/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
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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 generalpopulation 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 (consumerfriendly 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 diseaserelated symptoms has not been
established. Continued approval for this
indication may be contingent upon
verification of clinical benefit in
subsequent trials.’’ The consumerfriendly 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
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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 consumerfriendly disclosure (table 2): The ‘‘three
element’’ version of the consumerfriendly 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.
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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 DTCresearch@
fda.hhs.gov.
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 consumerfriendly 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 smallsized effects in the main study (table 3).
TABLE 1—STUDY 1 DESIGN
Physician-labeling version ................................
Consumer-friendly version ................................
High prominence
Low prominence
Absent
Condition 1 .............................
Condition 2 .............................
Condition 3 .............................
Condition 4.
Condition 5.
TABLE 2—STUDY 2 DESIGN
[Consumer-friendly disclosure elements]
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High prominence ...............
Approval basis
Approval basis + unknown
outcomes
Approval basis +
confirmatory trials
Condition 6 ........................
Condition 7 ........................
Condition 8 ........................
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
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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
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Approval basis + unknown
outcomes + confirmatory
trials
Study 1 Condition 2.
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
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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
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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
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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
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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 consumerfriendly 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 overdisclosure, 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.
16747
(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
respondents
khammond on DSKJM1Z7X2PROD with NOTICES
Activity
Number of
responses per
respondent
Total annual
responses
Pretest 1 and 2 screener ..........................................
Study 1 and 2 screener ............................................
Pretest 1 ...................................................................
Main Study 1 .............................................................
Pretest 2 ...................................................................
Main Study 2 .............................................................
3,600
20,600
100
630
80
400
1
1
1
1
1
1
3,600
20,600
100
630
80
400
Total ...................................................................
........................
........................
........................
1 There
Average burden
per response
0.08
0.08
0.33
0.33
0.33
0.33
(5 minutes) .......
(5 minutes) .......
(20 minutes) .....
(20 minutes) .....
(20 minutes) .....
(20 minutes) .....
288
1,648
33
208
26
132
...................................
2,335
are no capital costs or operating and maintenance costs associated with this collection of information.
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16748
Federal Register / Vol. 87, No. 57 / Thursday, March 24, 2022 / Notices
III. References
khammond on DSKJM1Z7X2PROD with NOTICES
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.
VerDate Sep<11>2014
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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
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Health Resources and Services
Administration
National Vaccine Injury Compensation
Program; List of Petitions Received
Health Resources and Services
Administration (HRSA), Department of
Health and Human Services (HHS).
ACTION: Notice.
AGENCY:
HRSA is publishing this
notice of petitions received under the
National Vaccine Injury Compensation
Program (the Program), as required by
Section 2112(b)(2) of the Public Health
Service (PHS) Act, as amended. While
the Secretary of HHS is named as the
respondent in all proceedings brought
by the filing of petitions for
compensation under the Program, the
United States Court of Federal Claims is
charged by statute with responsibility
for considering and acting upon the
petitions.
FOR FURTHER INFORMATION CONTACT: For
information about requirements for
filing petitions, and the Program in
general, contact Lisa L. Reyes, Clerk of
Court, United States Court of Federal
Claims, 717 Madison Place NW,
Washington, DC 20005, (202) 357–6400.
For information on HRSA’s role in the
Program, contact the Director, National
Vaccine Injury Compensation Program,
5600 Fishers Lane, Room 08N146B,
Rockville, Maryland 20857; (301) 443–
6593, or visit our website at: https://
www.hrsa.gov/vaccinecompensation/
index.html.
SUPPLEMENTARY INFORMATION: The
Program provides a system of no-fault
compensation for certain individuals
who have been injured by specified
childhood vaccines. Subtitle 2 of Title
XXI of the PHS Act, 42 U.S.C. 300aa–
10 et seq., provides that those seeking
compensation are to file a petition with
the United States Court of Federal
Claims and to serve a copy of the
petition to the Secretary of HHS, who is
named as the respondent in each
proceeding. The Secretary has delegated
this responsibility under the Program to
HRSA. The Court is directed by statute
to appoint special masters who take
evidence, conduct hearings as
SUMMARY:
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Frm 00045
Fmt 4703
Sfmt 4703
appropriate, and make initial decisions
as to eligibility for, and amount of,
compensation.
A petition may be filed with respect
to injuries, disabilities, illnesses,
conditions, and deaths resulting from
vaccines described in the Vaccine Injury
Table (the Table) set forth at 42 CFR
100.3. This Table lists for each covered
childhood vaccine the conditions that
may lead to compensation and, for each
condition, the time period for
occurrence of the first symptom or
manifestation of onset or of significant
aggravation after vaccine
administration. Compensation may also
be awarded for conditions not listed in
the Table and for conditions that are
manifested outside the time periods
specified in the Table, but only if the
petitioner shows that the condition was
caused by one of the listed vaccines.
Section 2112(b)(2) of the PHS Act, 42
U.S.C. 300aa–12(b)(2), requires that
‘‘[w]ithin 30 days after the Secretary
receives service of any petition filed
under section 2111 the Secretary shall
publish notice of such petition in the
Federal Register.’’ Set forth below is a
list of petitions received by HRSA on
February 1, 2022, through February 28,
2022. This list provides the name of
petitioner, city and state of vaccination
(if unknown then city and state of
person or attorney filing claim), and
case number. In cases where the Court
has redacted the name of a petitioner
and/or the case number, the list reflects
such redaction.
Section 2112(b)(2) also provides that
the special master ‘‘shall afford all
interested persons an opportunity to
submit relevant, written information’’
relating to the following:
1. The existence of evidence ‘‘that
there is not a preponderance of the
evidence that the illness, disability,
injury, condition, or death described in
the petition is due to factors unrelated
to the administration of the vaccine
described in the petition,’’ and
2. Any allegation in a petition that the
petitioner either:
a. ‘‘[S]ustained, or had significantly
aggravated, any illness, disability,
injury, or condition not set forth in the
Vaccine Injury Table but which was
caused by’’ one of the vaccines referred
to in the Table, or
b. ‘‘[S]ustained, or had significantly
aggravated, any illness, disability,
injury, or condition set forth in the
Vaccine Injury Table the first symptom
or manifestation of the onset or
significant aggravation of which did not
occur within the time period set forth in
the Table but which was caused by a
vaccine’’ referred to in the Table.
E:\FR\FM\24MRN1.SGM
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]]>Agencies
[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,
[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.
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 [email protected].
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
