Multiple Endpoints in Clinical Trials; Guidance for Industry; Availability, 64055-64057 [2022-22882]
Download as PDF
<![CDATA[
jspears on DSK121TN23PROD with NOTICES
Federal Register / Vol. 87, No. 203 / Friday, October 21, 2022 / Notices
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–
2017–D–6528 for ‘‘Refusal of Inspection
by a Foreign Food Establishment or
Foreign Government.’’ Received
comments 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.govinfo.gov/content/pkg/FR-201509-18/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.
VerDate Sep<11>2014
19:08 Oct 20, 2022
Jkt 259001
You may submit comments on any
guidance at any time (see 21 CFR
10.115(g)(5)).
Submit written requests for single
copies of the guidance to the
Compliance Policy Staff/Office of
Compliance, Center for Food Safety and
Applied Nutrition (HFS–605), Food and
Drug Administration, 5001 Campus Dr.,
College Park, MD 20740. Send two selfaddressed adhesive labels to assist that
office in processing your request. See
the SUPPLEMENTARY INFORMATION section
for electronic access to the guidance.
FOR FURTHER INFORMATION CONTACT:
Yinqing Ma, Center for Food Safety and
Applied Nutrition (HFS–605), Food and
Drug Administration, 5001 Campus Dr.,
College Park, MD 20740, 240–402–2479.
SUPPLEMENTARY INFORMATION:
I. Background
We are announcing the availability of
a guidance for industry entitled
‘‘Refusal of Inspection by a Foreign
Food Establishment or Foreign
Government.’’ We are issuing this
guidance consistent with our good
guidance practices regulation (21 CFR
10.115). The guidance represents the
current thinking of FDA on this topic.
It does not establish any rights for any
person and is not binding on FDA or the
public. You can use an alternative
approach if it satisfies the requirements
of the applicable statutes and
regulations.
In the Federal Register of December
12, 2017 (82 FR 58410), we made
available a draft guidance for industry
entitled ‘‘Refusal of Inspection by a
Foreign Food Establishment or Foreign
Government’’ and gave interested
parties an opportunity to submit
comments by February 26, 2018, for us
to consider before beginning work on
the final version of the guidance. We
received several comments on the draft
guidance and have modified the final
guidance where appropriate. Changes to
the guidance include: provided
additional information on FDA’s
inspection authority; clarified that the
investigator will inform the owner,
operator, or agent in charge of the
establishment when they consider their
action to be a refusal and will explain
the consequences of the refusal; and
clarified that the Agency will make the
final decision regarding refusal and
listing on Import Alert 99–32. In
addition, we made editorial changes to
improve clarity. The guidance
announced in this notice finalizes the
draft guidance dated December 2017.
II. Electronic Access
Persons with access to the internet
may obtain the guidance at either
PO 00000
Frm 00056
Fmt 4703
Sfmt 4703
64055
https://www.fda.gov/FoodGuidances or
https://www.regulations.gov. Use the
FDA website listed in the previous
sentence to find the most current
version of the guidance.
Dated: October 17, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022–22884 Filed 10–20–22; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA 2016–D–4460]
Multiple Endpoints in Clinical Trials;
Guidance for Industry; Availability
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice of availability.
The Food and Drug
Administration (FDA or Agency) is
announcing the availability of a final
guidance for industry entitled ‘‘Multiple
Endpoints in Clinical Trials.’’ This
guidance provides sponsors and review
staff with the Agency’s thinking about
the problems posed by multiple
endpoints in the analysis and
interpretation of study results and how
these problems can be managed in
clinical trials for human drugs,
including drugs subject to licensing as
biological products. This guidance
finalizes the draft guidance of the same
title issued on January 13, 2017.
DATES: The announcement of the
guidance is published in the Federal
Register on October 21, 2022.
ADDRESSES: You may submit comments
on any guidance at any time as follows:
SUMMARY:
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
E:\FR\FM\21OCN1.SGM
21OCN1
64056
Federal Register / Vol. 87, No. 203 / Friday, October 21, 2022 / Notices
jspears on DSK121TN23PROD with NOTICES
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 2016–
D–4460 for ‘‘Multiple Endpoints in
Clinical Trials.’’ Received comments
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, 240–402–7500.
• 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
VerDate Sep<11>2014
19:08 Oct 20, 2022
Jkt 259001
FR 56469, September 18, 2015, or access
the information at: https://
www.govinfo.gov/content/pkg/FR-201509-18/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, 240–402–7500.
You may submit comments on any
guidance at any time (see 21 CFR
10.115(g)(5)).
Submit written requests for single
copies of this guidance to the Division
of Drug Information, Center for Drug
Evaluation and Research, Food and
Drug Administration, 10001 New
Hampshire Ave., Hillandale Building,
4th Floor, Silver Spring, MD 20993–
0002 or to the Office of Communication,
Outreach and Development, Center for
Biologics Evaluation and Research
(CBER), Food and Drug Administration,
10903 New Hampshire Ave., Bldg. 71,
Rm. 3128, Silver Spring, MD 20993–
0002. Send one self-addressed adhesive
label to assist that office in processing
your requests. See the SUPPLEMENTARY
INFORMATION section for electronic
access to the guidance document.
FOR FURTHER INFORMATION CONTACT:
Scott N. Goldie, Center for Drug
Evaluation and Research, Office of
Biostatistics, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 21, Rm. 3557, Silver Spring,
MD 20993–0002, 301–796–2055, or
Stephen Ripley, Center for Biologics
Evaluation and Research, Food and
Drug Administration, 10903 New
Hampshire Ave., Bldg. 71, Rm. 7301,
Silver Spring, MD 20993–0002, 240–
402–7911.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of
a guidance for industry entitled
‘‘Multiple Endpoints in Clinical Trials.’’
This guidance describes various
strategies for grouping and ordering
endpoints for analysis of a drug’s effects
and applying some well-recognized
statistical methods for managing
multiplicity within a clinical trial to
control the chance of making erroneous
conclusions about a drug’s effects.
FDA’s International Conference on
Harmonization (ICH) guidance for
industry ‘‘E9 Statistical Principles for
Clinical Trials’’ is a broad-ranging
guidance that includes discussion of
PO 00000
Frm 00057
Fmt 4703
Sfmt 4703
multiple endpoints. This guidance
provides greater detail on the topic of
multiple endpoints.
Failure to account for multiplicity
when there are several clinical
endpoints evaluated in a clinical trial
can lead to false positive conclusions
regarding the effects of the drug. The
regulatory concern regarding
multiplicity arises principally in the
evaluation of clinical trials intended to
demonstrate effectiveness and support
drug approval; however, this issue is
important throughout the drug
development process.
The focus of this guidance is control
of the Type 1 error rate for the planned
primary and secondary endpoints of a
clinical trial so that the major findings
are well supported. Multiplicity
adjustments provide a means for
controlling the Type 1 error rate when
there are multiple analyses of the drug’s
effects. The issues of multiplicity and
methods to address them are illustrated
in the guidance with examples of
different study endpoints. Both the
issues and methods that apply to
multiple endpoints also apply to other
sources of multiplicity, including
multiple doses, time points, or study
population subgroups.
This guidance finalizes the draft
guidance of the same title that
published January 13, 2017 (82 FR
4353). FDA considered comments
received on the draft guidance as the
guidance was finalized. Changes from
the draft to the final guidance include
clarifications for some of the potential
issues caused by including multiple
endpoints in clinical trials and
clarifications for some of the strategies
for handling these issues. In addition,
editorial changes were made to improve
clarity by reducing redundancies in the
text.
This guidance is being issued
consistent with FDA’s good guidance
practices regulation (21 CFR 10.115).
The guidance represents the current
thinking of FDA on ‘‘Multiple
Endpoints in Clinical Trials.’’ It does
not establish any rights for any person
and is not binding on FDA or the public.
You can use an alternative approach if
it satisfies the requirements of the
applicable statutes and regulations.
II. Paperwork Reduction Act of 1995
While this guidance contains no
collection of information, it does refer to
previously approved FDA collections of
information. Therefore, clearance by the
Office of Management and Budget
(OMB) under the Paperwork Reduction
Act of 1995 (PRA) (44 U.S.C. 3501–
3521) is not required for this guidance.
The previously approved collections of
E:\FR\FM\21OCN1.SGM
21OCN1
Federal Register / Vol. 87, No. 203 / Friday, October 21, 2022 / Notices
information are subject to review by
OMB under the PRA. The collections of
information in 21 CFR 312.23 for the
content and format of investigational
new drug applications have been
approved under OMB control number
0910–0014. The collections of
information in 21 CFR part 314 for
submitting applications for FDA
approval to market a new drug have
been approved under OMB control
number 0910–0001. The collections of
information in 21 CFR 201.56 and
201.57 for preparing and submitting
labeling have been approved under
OMB control number 0910–0572.
III. Electronic Access
Persons with access to the internet
may obtain the guidance at https://
www.fda.gov/drugs/guidancecompliance-regulatory-information/
guidances-drugs, https://www.fda.gov/
regulatory-information/search-fdaguidance-documents, or https://
www.regulations.gov.
Dated: October 17, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022–22882 Filed 10–20–22; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2022–D–1061]
Select Updates for the Breakthrough
Devices Program Guidance: Reducing
Disparities in Health and Healthcare;
Draft Guidance for Industry and Food
and Drug Administration Staff;
Availability
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice of availability.
The Food and Drug
Administration (FDA or Agency) is
announcing the availability of the draft
guidance entitled ‘‘Select Updates for
the Breakthrough Devices Program
Guidance: Reducing Disparities in
Health and Healthcare.’’ FDA has
developed this draft guidance to
propose select updates to the guidance
that clarify how the program may be
applicable to certain medical devices
that provide for more effective treatment
or diagnosis of life-threatening or
irreversibly debilitating diseases or
conditions in populations impacted by
health and/or healthcare disparities.
This draft guidance is not final nor is it
for implementation at this time.
jspears on DSK121TN23PROD with NOTICES
SUMMARY:
VerDate Sep<11>2014
19:08 Oct 20, 2022
Jkt 259001
Submit either electronic or
written comments on the draft guidance
by December 20, 2022 to ensure that the
Agency considers your comment on this
draft guidance before it begins work on
the final version of the guidance.
ADDRESSES: You may submit comments
on any guidance at any time as follows:
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
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–
2022–D–1061 for ‘‘Select Updates for
the Breakthrough Devices Program
Guidance: Reducing Disparities in
Health and Healthcare.’’ Received
comments 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, 240–402–7500.
PO 00000
Frm 00058
Fmt 4703
Sfmt 4703
64057
• 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.govinfo.gov/content/pkg/FR-201509-18/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, 240–402–7500.
You may submit comments on any
guidance at any time (see 21 CFR
10.115(g)(5)).
An electronic copy of the guidance
document is available for download
from the internet. See the
SUPPLEMENTARY INFORMATION section for
information on electronic access to the
guidance. Submit written requests for a
single hard copy of the draft guidance
document entitled ‘‘Select Updates for
the Breakthrough Devices Program
Guidance: Reducing Disparities in
Health and Healthcare’’ to the Office of
Policy, Center for Devices and
Radiological Health, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 5431, Silver Spring,
MD 20993–0002; or the Office of
Communication, Outreach, and
Development, Center for Biologics
Evaluation and Research, Food and
E:\FR\FM\21OCN1.SGM
21OCN1
]]>Agencies
[Federal Register Volume 87, Number 203 (Friday, October 21, 2022)]
[Notices]
[Pages 64055-64057]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-22882]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA 2016-D-4460]
Multiple Endpoints in Clinical Trials; Guidance for Industry;
Availability
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of availability.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
the availability of a final guidance for industry entitled ``Multiple
Endpoints in Clinical Trials.'' This guidance provides sponsors and
review staff with the Agency's thinking about the problems posed by
multiple endpoints in the analysis and interpretation of study results
and how these problems can be managed in clinical trials for human
drugs, including drugs subject to licensing as biological products.
This guidance finalizes the draft guidance of the same title issued on
January 13, 2017.
DATES: The announcement of the guidance is published in the Federal
Register on October 21, 2022.
ADDRESSES: You may submit comments on any guidance at any time as
follows:
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
[[Page 64056]]
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 2016-D-4460 for ``Multiple Endpoints in Clinical Trials.'' Received
comments 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, 240-402-7500.
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.govinfo.gov/content/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, 240-402-7500.
You may submit comments on any guidance at any time (see 21 CFR
10.115(g)(5)).
Submit written requests for single copies of this guidance to the
Division of Drug Information, Center for Drug Evaluation and Research,
Food and Drug Administration, 10001 New Hampshire Ave., Hillandale
Building, 4th Floor, Silver Spring, MD 20993-0002 or to the Office of
Communication, Outreach and Development, Center for Biologics
Evaluation and Research (CBER), Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002. Send
one self-addressed adhesive label to assist that office in processing
your requests. See the SUPPLEMENTARY INFORMATION section for electronic
access to the guidance document.
FOR FURTHER INFORMATION CONTACT: Scott N. Goldie, Center for Drug
Evaluation and Research, Office of Biostatistics, Food and Drug
Administration, 10903 New Hampshire Ave., Bldg. 21, Rm. 3557, Silver
Spring, MD 20993-0002, 301-796-2055, or Stephen Ripley, Center for
Biologics Evaluation and Research, Food and Drug Administration, 10903
New Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002,
240-402-7911.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a guidance for industry
entitled ``Multiple Endpoints in Clinical Trials.'' This guidance
describes various strategies for grouping and ordering endpoints for
analysis of a drug's effects and applying some well-recognized
statistical methods for managing multiplicity within a clinical trial
to control the chance of making erroneous conclusions about a drug's
effects. FDA's International Conference on Harmonization (ICH) guidance
for industry ``E9 Statistical Principles for Clinical Trials'' is a
broad-ranging guidance that includes discussion of multiple endpoints.
This guidance provides greater detail on the topic of multiple
endpoints.
Failure to account for multiplicity when there are several clinical
endpoints evaluated in a clinical trial can lead to false positive
conclusions regarding the effects of the drug. The regulatory concern
regarding multiplicity arises principally in the evaluation of clinical
trials intended to demonstrate effectiveness and support drug approval;
however, this issue is important throughout the drug development
process.
The focus of this guidance is control of the Type 1 error rate for
the planned primary and secondary endpoints of a clinical trial so that
the major findings are well supported. Multiplicity adjustments provide
a means for controlling the Type 1 error rate when there are multiple
analyses of the drug's effects. The issues of multiplicity and methods
to address them are illustrated in the guidance with examples of
different study endpoints. Both the issues and methods that apply to
multiple endpoints also apply to other sources of multiplicity,
including multiple doses, time points, or study population subgroups.
This guidance finalizes the draft guidance of the same title that
published January 13, 2017 (82 FR 4353). FDA considered comments
received on the draft guidance as the guidance was finalized. Changes
from the draft to the final guidance include clarifications for some of
the potential issues caused by including multiple endpoints in clinical
trials and clarifications for some of the strategies for handling these
issues. In addition, editorial changes were made to improve clarity by
reducing redundancies in the text.
This guidance is being issued consistent with FDA's good guidance
practices regulation (21 CFR 10.115). The guidance represents the
current thinking of FDA on ``Multiple Endpoints in Clinical Trials.''
It does not establish any rights for any person and is not binding on
FDA or the public. You can use an alternative approach if it satisfies
the requirements of the applicable statutes and regulations.
II. Paperwork Reduction Act of 1995
While this guidance contains no collection of information, it does
refer to previously approved FDA collections of information. Therefore,
clearance by the Office of Management and Budget (OMB) under the
Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521) is not
required for this guidance. The previously approved collections of
[[Page 64057]]
information are subject to review by OMB under the PRA. The collections
of information in 21 CFR 312.23 for the content and format of
investigational new drug applications have been approved under OMB
control number 0910-0014. The collections of information in 21 CFR part
314 for submitting applications for FDA approval to market a new drug
have been approved under OMB control number 0910-0001. The collections
of information in 21 CFR 201.56 and 201.57 for preparing and submitting
labeling have been approved under OMB control number 0910-0572.
III. Electronic Access
Persons with access to the internet may obtain the guidance at
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, or https://www.regulations.gov.
Dated: October 17, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-22882 Filed 10-20-22; 8:45 am]
BILLING CODE 4164-01-P
