[Federal Register Volume 83, Number 201 (Wednesday, October 17, 2018)]
[Notices]
[Pages 52478-52481]
[FR Doc No: 2018-22570]

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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2018-N-3138]

Agency Information Collection Activities; Proposed Collection;
Comment Request; Experimental Study of an Accelerated Approval
Disclosure

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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

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 research entitled ``Experimental Study of
an Accelerated Approval Disclosure.'' This study will examine the
presence, wording, and prominence of a disclosure communicating
information related to the drug's accelerated approval in direct-to-
consumer (DTC) promotional materials.

DATES: Submit either electronic or written comments on the collection
of information by December 17, 2018.

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 December 17, 2018. The https://www.regulations.gov electronic filing system will accept comments until
midnight Eastern Time at the end of December 17, 2018. Comments
received by mail/hand delivery/courier (for written/paper 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:
     Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to https://www.regulations.gov
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 https://www.regulations.gov.
     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:
     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.
     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-2018-N-3138 for ``Experimental Study of an Accelerated Approval
Disclosure'' 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 https://www.regulations.gov or at the Dockets Management Staff between 9 a.m.
and 4 p.m., Monday through Friday.
     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 https://www.regulations.gov.
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: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to https://www.regulations.gov 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.

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,<PHONE_NUMBER>,
[email protected].

SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3520), 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.

Experimental Study of an Accelerated Approval Disclosure

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
information is truthful, balanced, and accurately communicated so that
patients and health care providers can make informed decisions about
treatment options. The OPDP's research program supports this mission by
providing 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 we believe 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 research data through analytical methodology development and
investigation of sampling and response issues. This study falls under
the topic of advertising features (content and format).
    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) (21 U.S.C. 355 (c)) of the FD&C Act 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 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'' (2014 Guidance for Industry:
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's regulations governing physician labeling for
prescription drugs, the INDICATIONS AND USAGE section of the FDA-
approved prescribing information (PI) for a drug approved under
accelerated approval must include a succinct description of the
limitations of usefulness of the drug and any uncertainty about
anticipated clinical benefits, with reference to the clinical studies
section for a discussion of the available evidence (21 CFR
201.57(c)(2)(i)(B)). Therefore, the PI for accelerated approval
products typically satisfies this requirement by including a statement
in the INDICATIONS AND USAGE section about the product's approval under
the accelerated approval pathway. In a draft guidance, FDA recommended
that the INDICATIONS AND USAGE section for drugs approved under
accelerated approval should generally describe three elements:
indication(s), limitations of usefulness and clinical benefit
uncertainty, and continued approval (Ref. 2). As the PI is intended for
healthcare professionals, the information related to a drug's
accelerated approval generally includes complex concepts and
sophisticated wording. For example, PIs for accelerated approval
products include language such as:
     This indication is approved under accelerated approval
based on [surrogate endpoint]. An improvement in survival or disease-
related symptoms has not been established. Continued approval for this
indication may be contingent upon verification and description of
clinical benefit in the confirmatory trial; or
     Approval is based on a reduction in [surrogate endpoint].
There are no controlled trials demonstrating a direct treatment benefit
such as improvement in disease-related symptoms, functioning, or
increased survival.
    Despite its complexity, sponsors often use this language from the
PI in DTC promotional materials for drugs approved under accelerated
approval. In other cases, DTC promotion of accelerated approval
products does not communicate the unique considerations and potential
limitations inherent in the accelerated approval process.
    Disclosures may be used to communicate such information to
consumers. Disclosures can include information about scientific and
clinical data, any residual uncertainty about clinical benefit, and the
practical utility of scientific and clinical data. These disclosures
may influence consumer comprehension and affect perception of drug's
risks and benefits. This study will examine the presence, wording, and
prominence of a disclosure communicating information related to the
drug's accelerated approval in DTC promotional materials. This
information includes the use of surrogate or intermediate clinical
endpoints to support approval, the uncertainty about the relationship
of the surrogate or intermediate clinical endpoint to the predicted
clinical benefit, and the need for confirmatory trials.
    We plan to conduct one pretest not longer than 20 minutes,
administered via internet panel, to test the experimental manipulations
and pilot the main study procedures. After implementing any lessons
learned from the pilot, we then plan to conduct one main study not
longer than 20 minutes, administered via internet panel. For the
pretest and main study, we will randomly assign the voluntary
participants to one of the test conditions (see table 1 for the study
design). We have chosen to focus on oncology products because cancer is
a life-threatening illness, and many oncology products are granted
accelerated approval. Moreover, DTC promotion of oncology drugs is
common. In the study, participants will view a website for a fictional
oncology prescription drug. After viewing the website, participants
will complete a questionnaire that assesses whether participants
noticed the disclosure and their interpretation 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].
    We will vary the presence and prominence of the disclosure (e.g.,
size, color, and location). 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 will vary whether
the disclosure is written in consumer-friendly language or uses
language, in use by many sponsors, which is the same as or similar to
that directed at healthcare professionals in FDA-approved prescription
drug labeling for accelerated approval products. The consumer-friendly
version of the accelerated approval disclosure will be based on
consumer feedback elicited in focus groups conducted prior to the
pretest (approved under OMB control number 0910-0695). The physician
labeling version of the accelerated approval disclosure will be drawn
from FDA-approved physician labeling. We 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. To test these hypotheses, we will conduct
inferential statistical tests such as logistic regression and analysis
of variance.

                                              Table 1--Study Design
----------------------------------------------------------------------------------------------------------------
                                                          High prominence     Low prominence         Absent
----------------------------------------------------------------------------------------------------------------
Physician labeling version.............................
Consumer-friendly version..............................
----------------------------------------------------------------------------------------------------------------

    We will recruit a general population sample of adult volunteers 18
years of age or older. 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. We will use
health literacy quotas to ensure that our sample includes participants
with a range of health literacy skills. With the sample sizes described
below, we will have sufficient power to detect small-sized effects in
the main study (table 2).
    FDA estimates the burden of this collection of information as
follows:

                                                     Table 2--Estimated Annual Reporting Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                   Number of
                   Activity                        Number of     responses per   Total annual          Average burden per response          Total hours
                                                  respondents     respondent       responses
--------------------------------------------------------------------------------------------------------------------------------------------------------
Pretest screener..............................             916               1               1  0.08 (5 min.)...........................           73.28
Study screener................................           1,507               1               1  0.08 (5 min.)...........................          120.56
Pretest.......................................             385               1               1  0.33 (20 min.)..........................          127.05
Main Study....................................             633               1               1  0.33 (20 min.)..........................          208.89
                                               ---------------------------------------------------------------------------------------------------------
    Total.....................................  ..............  ..............  ..............  ........................................          529.78
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

References

    The following references are on display at the Dockets Management
Staff, Food and Drug Administration, 5630 Fishers Lane, Rm. 1061,
Rockville, MD 20857, and is available for viewing by interested persons
between 9 a.m. and 4 p.m., Monday through Friday; the reference marked
with an asterisk is also available electronically at https://www.regulations.gov. The reference without an asterisk is not on public
display at https://www.regulations.gov because it has copyright
restriction, or it is available as a published article. FDA has
verified the website address, 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. doi:10.1001/jamaoncol.2017.5618.
2. FDA Draft Guidance for Industry: Labeling for Human Prescription
Drug and Biological Products Approved Under the Accelerated Approval
Pathway (March 2014) (https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM390058.pdf).

    Dated: October 11, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-22570 Filed 10-16-18; 8:45 am]
 BILLING CODE 4164-01-P