Agency Information Collection Activities; Proposed Collection; Comment Request; Accelerated Approval Disclosures on Direct-to-Consumer Prescription Drug Websites

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Published

June 11, 2021

Issuing agencies

Health and Human Services DepartmentFood and Drug Administration

Abstract

The Food and Drug Administration (FDA, Agency, or we) is announcing an opportunity for public comment on the proposed collection of certain information by the Agency. Under the Paperwork Reduction Act of 1995 (PRA), Federal Agencies are required to publish notice in the Federal Register concerning each proposed collection of information and to allow 60 days for public comment in response to the notice. This notice solicits comments on the proposed study entitled ``Accelerated Approval Disclosures on Direct-to-Consumer Prescription Drug websites.''

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<title>Federal Register, Volume 86 Issue 111 (Friday, June 11, 2021)</title>
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[Federal Register Volume 86, Number 111 (Friday, June 11, 2021)]
[Notices]
[Pages 31323-31327]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2021-12264]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

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

Agency Information Collection Activities; Proposed Collection;
Comment Request; Accelerated Approval Disclosures on Direct-to-Consumer
Prescription Drug Websites

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is
announcing an opportunity for public comment on the proposed collection
of certain information by the Agency. Under the Paperwork Reduction Act
of 1995 (PRA), Federal Agencies are required to publish notice in the
Federal Register concerning each proposed collection of information and
to allow 60 days for public comment in response to the notice. This
notice solicits comments on the proposed study entitled ``Accelerated
Approval Disclosures on Direct-to-Consumer Prescription Drug
websites.''

DATES: Submit either electronic or written comments on the collection
of information by August 10, 2021.

ADDRESSES: You may submit comments as follows. Please note that late,
untimely filed comments will not be considered. Electronic comments
must be submitted on or before August 10, 2021. The <a href="https://www.regulations.gov">https://www.regulations.gov</a> electronic filing system will accept comments until
11:59 p.m. Eastern Time at the end of August 10, 2021. Comments
received by mail/hand delivery/courier (for written/paper

[[Page 31324]]

submissions) will be considered timely if they are postmarked or the
delivery service acceptance receipt is on or before that date.

Electronic Submissions

Submit electronic comments in the following way:
<bullet> Federal eRulemaking Portal: <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to <a href="https://www.regulations.gov">https://www.regulations.gov</a>
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
<bullet> If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

Submit written/paper submissions as follows:
<bullet> Mail/Hand Delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
<bullet> For written/paper comments submitted to the Dockets
Management Staff, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-2021-N-0371 for ``Agency Information Collection Activities;
Proposed Collection; Comment Request; Accelerated Approval Disclosures
on Direct-to-Consumer Prescription Drug websites.'' Received comments,
those filed in a timely manner (see ADDRESSES), will be placed in the
docket and, except for those submitted as ``Confidential Submissions,''
publicly viewable at <a href="https://www.regulations.gov">https://www.regulations.gov</a> or at the Dockets
Management Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-
402-7500.
<bullet> Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Submit both copies to the Dockets Management Staff. If you do not wish
your name and contact information to be made publicly available, you
can provide this information on the cover sheet and not in the body of
your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law. For more information about FDA's posting of
comments to public dockets, see 80 FR 56469, September 18, 2015, or
access the information at: <a href="https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf">https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf</a>.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852, 240-402-7500.

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#653537243611040303250301044b0d0d164b020a13"><span class="__cf_email__" data-cfemail="59090b180a2d383f3f193f3d387731312a773e362f">[email&#160;protected]</span></a>. The questionnaire is available upon request from
<a href="/cdn-cgi/l/email-protection#88ccdccbdaedfbede9faebe0c8eeece9a6e0e0fba6efe7fe"><span class="__cf_email__" data-cfemail="4b0f1f08192e382e2a3928230b2d2f2a65232338652c243d">[email&#160;protected]</span></a>.

SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3521), Federal
Agencies must obtain approval from the Office of Management and Budget
(OMB) for each collection of information they conduct or sponsor.
``Collection of information'' is defined in 44 U.S.C. 3502(3) and 5 CFR
1320.3(c) and includes Agency requests or requirements that members of
the public submit reports, keep records, or provide information to a
third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A))
requires Federal Agencies to provide a 60-day notice in the Federal
Register concerning each proposed collection of information before
submitting the collection to OMB for approval. To comply with this
requirement, FDA is publishing notice of the proposed collection of
information set forth in this document.
With respect to the following collection of information, FDA
invites comments on these topics: (1) Whether the proposed collection
of information is necessary for the proper performance of FDA's
functions, including whether the information will have practical
utility; (2) the accuracy of FDA's estimate of the burden of the
proposed collection of information, including the validity of the
methodology and assumptions used; (3) ways to enhance the quality,
utility, and clarity of the information to be collected; and (4) ways
to minimize the burden of the collection of information on respondents,
including through the use of automated collection techniques, when
appropriate, and other forms of information technology.

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 (42 U.S.C.
300u(a)(4)) authorizes the 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

[[Page 31325]]

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: <a href="https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/office-prescription-drug-promotion-opdp-research">https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/office-prescription-drug-promotion-opdp-research</a>. The
website includes links to the latest Federal Register notices and peer-
reviewed publications produced by our office. The website maintains
information on studies we have conducted, dating back to a direct-to-
consumer (DTC) survey conducted in 1999.

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 or a biological product
under section 351(a) of the Public Health Service 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 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 2014 guidance for industry
entitled ``Expedited Programs for Serious Conditions--Drugs and
Biologics,'' available at <a href="https://www.fda.gov/downloads/Drugs/Guidances/UCM358301.pdf">https://www.fda.gov/downloads/Drugs/Guidances/UCM358301.pdf</a>). 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 (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 . . .'' (21 CFR
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 Pathway,'' available at <a href="https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM390058.pdf">https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM390058.pdf</a>).
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 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.

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

[[Page 31326]]

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.
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" class="__cf_email__" data-cfemail="3c78687f4e594f595d4e5f547c5a585d1254544f125b534a">[email&#160;protected]</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 health care, 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
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High prominence Low prominence Absent
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Physician-labeling version.......... Condition 1............ Condition 3........... Condition 5.
Consumer-friendly version........... Condition 2............ Condition 4...........
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Table 2--Study 2 Design
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Consumer-friendly disclosure elements
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Approval basis +
Approval basis + Approval basis + unknown outcomes +
Approval basis unknown outcomes confirmatory confirmatory
trials trials
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High prominence................. Condition 6....... Condition 7....... Condition 8....... Study 1 Condition
2.
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FDA estimates the burden of this collection of information as
follows:

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

References

The following references marked with an asterisk (*) are on display
at the Dockets Management Staff (see ADDRESSES), and are available for
viewing by interested persons between 9 a.m. and 4 p.m., Monday through
Friday; they also are available electronically at <a href="https://www.regulations.gov">https://www.regulations.gov</a>. References without asterisks are not on public
display at <a href="https://www.regulations.gov">https://www.regulations.gov</a> because they have copyright
restriction. Some may be available at the website address, if listed.
References without asterisks are available for viewing only at the
Dockets Management Staff. FDA has verified the website addresses, as of
the date this document publishes in the Federal Register, but websites
are subject to change over time.

1. Beaver J.A., L.J. Howie L.J., L. Pelosof L, 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. doi:10.1001/
jamaoncol.2017.5618
2. Sullivan H.W., A.C. O'Donoghue, K.T. David, N.J. Patel.
``Disclosing Accelerated Approval on Direct-to-Consumer Prescription
Drug Websites.'' Pharmacoepidemiology and Drug Safety. 2018;27:1277-
1280. <a href="https://doi.org/10.1002/pds.4664">https://doi.org/10.1002/pds.4664</a>

Dated: June 2, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2021-12264 Filed 6-10-21; 8:45 am]
BILLING CODE 4164-01-P

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