Agency Information Collection Activities; Proposed Collection; Comment Request; Experimental Study of an Accelerated Approval Disclosure, 52478-52481 [2018-22570]
Download as PDF
<![CDATA[
daltland on DSKBBV9HB2PROD with NOTICES
52478
Federal Register / Vol. 83, No. 201 / Wednesday, October 17, 2018 / Notices
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:
Christine Lincoln, Center for Drug
Evaluation and Research, Food and
Drug Administration, 10903 New
Hampshire Ave. Bldg. 22, Rm. 2118,
Silver Spring, MD 20993–0002, email:
Christine.Lincoln@fda.hhs.gov.
SUPPLEMENTARY INFORMATION: The use of
tumor genetic profiling in cancer
treatment decision making has
transformed therapeutic strategies in
many adult cancers. Extension of this
approach to treatment decision making
for children with cancer, however, has
been greatly diminished due to delays
in evaluation of potentially active drugs.
Until the passage of section 504 of
FDARA, section 505B of the FD&C Act
(21 U.S.C. 355c) has not typically been
a useful mechanism to require the
development of drugs for pediatric
cancers, since most of the oncology
drugs approved for adults are used to
treat cancers that very rarely or never
occur in children (e.g. cancers of the
lung, prostate and breast). Therefore,
historically, drug sponsors have
requested and obtained waivers for
conducting the required assessments of
these drugs in pediatric patients.
Additionally, drugs developed for rare
cancer indications that received orphan
designation are exempted from the preFDARA requirement to conduct
pediatric assessments—even if the
cancers those products are intended to
treat occur in both adult and pediatric
patients—due to the fact that the orphan
designation exempts them from such
studies (see section 505B(k) of the FD&C
Act). However, FDARA amended
section 505B so that the requirement for
pediatric investigations of drugs
directed at molecular targets determined
to be substantially relevant to the
growth and progression of a pediatric
cancer apply even when the adult
indication has received an orphan
designation, or when the adult
indication does not occur, in the
pediatric population (e.g., prostate
cancer).
Although requirements to study
investigational therapies in pediatric
oncology were exceedingly rare, other
incentives have been put into place to
promote the development of oncology
products for pediatric cancer. Section
505A of the FD&C Act (21 U.S.C. 355a)
provides incentives, in the form of 6
months of additional marketing
VerDate Sep<11>2014
19:46 Oct 16, 2018
Jkt 247001
exclusivity, to encourage sponsors of
investigational therapies to conduct
pediatric studies of medicines with the
potential for use in children. To date,
section 505A has been one of the few
mechanisms available to incentivize
evaluation of new oncology products in
children and adolescents. Nevertheless,
further development of more novel
products that address the substantial
unmet needs of the pediatric population
is needed.
Section 504 of FDARA requires FDA,
with input from the National Cancer
Institute (NCI) and others, to develop
and regularly update: (1) A list of
molecular targets that are determined to
be substantially relevant to the growth
and progression of a pediatric cancer,
and that may trigger the requirement for
pediatric investigations under section
505B of the FD&C Act, and (2) a list of
molecular targets of new cancer drugs
and biological products in development
for which the requirement for pediatric
investigations under section 505B of the
FD&C Act would be automatically
waived.
To date, a total of 205 candidate
molecular targets were identified from
peer-reviewed literature searches,
review of publicly available genomic
databases, such as NCI Genomic Data
Commons, TARGET (Therapeutically
Applicable Research to Generate
Effective Targets), St. Jude PeCan Data
Portal, Ped PanCan, and INFORM
(Individualized Therapy for Relapsed
Malignancies in Childhood), and input
from international subject matter
experts. Of these, 62 (30.3 percent)
target a gene abnormality, 40 (19.5
percent) target a cell lineage
determinant, 21 (10.2 percent) target the
tumor microenvironment or the immune
system, and 77 (37.6 percent) are
classified as ‘‘Others.’’ Five (2.4 percent)
are candidates for automatic waivers.
Dated: October 11, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018–22565 Filed 10–16–18; 8:45 am]
BILLING CODE 4164–01–P
PO 00000
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.
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.
SUMMARY:
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.
DATES:
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
Frm 00103
Fmt 4703
Sfmt 4703
E:\FR\FM\17OCN1.SGM
17OCN1
Federal Register / Vol. 83, No. 201 / Wednesday, October 17, 2018 / Notices
daltland on DSKBBV9HB2PROD with NOTICES
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
VerDate Sep<11>2014
19:46 Oct 16, 2018
Jkt 247001
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/201523389.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, 301–796–7726, PRAStaff@
fda.hhs.gov.
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
PO 00000
Frm 00104
Fmt 4703
Sfmt 4703
52479
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
E:\FR\FM\17OCN1.SGM
17OCN1
daltland on DSKBBV9HB2PROD with NOTICES
52480
Federal Register / Vol. 83, No. 201 / Wednesday, October 17, 2018 / Notices
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
VerDate Sep<11>2014
19:46 Oct 16, 2018
Jkt 247001
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
PO 00000
Frm 00105
Fmt 4703
Sfmt 4703
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 lifethreatening 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 DTCresearch@
fda.hhs.gov.
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 consumerfriendly language or uses language, in
use by many sponsors, which is the
same as or similar to that directed at
healthcare professionals in FDAapproved 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.
E:\FR\FM\17OCN1.SGM
17OCN1
Federal Register / Vol. 83, No. 201 / Wednesday, October 17, 2018 / Notices
52481
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 smallsized 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
respondents
Activity
Average
burden per
response
Total annual
responses
Pretest screener ...........................................................
Study screener .............................................................
Pretest ..........................................................................
Main Study ...................................................................
916
1,507
385
633
1
1
1
1
1
1
1
1
Total ......................................................................
........................
........................
........................
1 There
0.08
0.08
0.33
0.33
Total
hours
(5 min.) .........
(5 min.) .........
(20 min.) .......
(20 min.) .......
73.28
120.56
127.05
208.89
...............................
529.78
are no capital costs or operating and maintenance costs associated with this collection of information.
References
daltland on DSKBBV9HB2PROD with NOTICES
Number of
responses per
respondent
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/GuidanceCompliance
RegulatoryInformation/Guidances/
UCM390058.pdf).
VerDate Sep<11>2014
19:46 Oct 16, 2018
Jkt 247001
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
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2017–E–6541]
Determination of Regulatory Review
Period for Purposes of Patent
Extension; DUPIXENT
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA or the Agency) has
determined the regulatory review period
for DUPIXENT and is publishing this
notice of that determination as required
by law. FDA has made the
determination because of the
submission of an application to the
Director of the U.S. Patent and
Trademark Office (USPTO), Department
of Commerce, for the extension of a
patent which claims that human
biological product.
DATES: Anyone with knowledge that any
of the dates as published (see the
SUPPLEMENTARY INFORMATION section) are
incorrect may submit either electronic
or written comments and ask for a
redetermination by December 17, 2018.
SUMMARY:
PO 00000
Frm 00106
Fmt 4703
Sfmt 4703
Furthermore, any interested person may
petition FDA for a determination
regarding whether the applicant for
extension acted with due diligence
during the regulatory review period by
April 15, 2019. See ‘‘Petitions’’ in the
SUPPLEMENTARY INFORMATION section for
more information.
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 11:59 p.m. 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
E:\FR\FM\17OCN1.SGM
17OCN1
]]>Agencies
[Federal Register Volume 83, Number 201 (Wednesday, October 17, 2018)]
[Notices]
[Pages 52478-52481]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[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
[[Page 52479]]
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, 301-796-7726,
[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
[[Page 52480]]
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.
[[Page 52481]]
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
