Notice2021-16929
Nonmetastatic Castration-Resistant Prostate Cancer: Considerations for Metastasis-Free Survival Endpoint in Clinical Trials; Guidance for Industry; Availability
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Published
August 9, 2021
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled "Nonmetastatic Castration-Resistant Prostate Cancer: Considerations for Metastasis-Free Survival Endpoint in Clinical Trials." Recent approvals of several drug products for patients with nonmetastatic castration-resistant prostate cancer have been supported by randomized clinical trials demonstrating improvements in metastasis-free survival. This guidance intends to inform potential future applicants regarding the Agency's expectations for collection, analysis, and reporting of data pertaining to metastasis-free survival. This guidance finalizes the draft guidance of the same title issued on November 14, 2018.
Full Text
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<title>Federal Register, Volume 86 Issue 150 (Monday, August 9, 2021)</title>
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[Federal Register Volume 86, Number 150 (Monday, August 9, 2021)]
[Notices]
[Pages 43551-43552]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2021-16929]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2018-D-3931]
Nonmetastatic Castration-Resistant Prostate Cancer:
Considerations for Metastasis-Free Survival Endpoint in Clinical
Trials; Guidance for Industry; Availability
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of availability.
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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
the availability of a final guidance for industry entitled
``Nonmetastatic Castration-Resistant Prostate Cancer: Considerations
for Metastasis-Free Survival Endpoint in Clinical Trials.'' Recent
approvals of several drug products for patients with nonmetastatic
castration-resistant prostate cancer have been supported by randomized
clinical trials demonstrating improvements in metastasis-free survival.
This guidance intends to inform potential future applicants regarding
the Agency's expectations for collection, analysis, and reporting of
data pertaining to metastasis-free survival. This guidance finalizes
the draft guidance of the same title issued on November 14, 2018.
DATES: The announcement of the guidance is published in the Federal
Register on August 9, 2021.
ADDRESSES: You may submit either electronic or written comments on
Agency guidances at any time as follows:
Electronic Submissions
Submit electronic comments in the following way:
<bullet> Federal eRulemaking Portal: <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to <a href="https://www.regulations.gov">https://www.regulations.gov</a>
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
<bullet> If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').
Written/Paper Submissions
Submit written/paper submissions as follows:
<bullet> Mail/Hand Delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
<bullet> For written/paper comments submitted to the Dockets
Management Staff, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-2018-D-3931 for ``Nonmetastatic Castration-Resistant Prostate
Cancer: Considerations for Metastasis-Free Survival Endpoint in
Clinical Trials.'' Received comments will be placed in the docket and,
except for those submitted as ``Confidential Submissions,'' publicly
viewable at <a href="https://www.regulations.gov">https://www.regulations.gov</a> or at the Dockets Management
Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-402-7500.
<bullet> Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper
[[Page 43552]]
submission. You should submit two copies total. One copy will include
the information you claim to be confidential with a heading or cover
note that states ``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.''
The Agency will review this copy, including the claimed confidential
information, in its consideration of comments. The second copy, which
will have the claimed confidential information redacted/blacked out,
will be available for public viewing and posted on <a href="https://www.regulations.gov">https://www.regulations.gov</a>. Submit both copies to the Dockets Management
Staff. If you do not wish your name and contact information to be made
publicly available, you can provide this information on the cover sheet
and not in the body of your comments and you must identify this
information as ``confidential.'' Any information marked as
``confidential'' will not be disclosed except in accordance with 21 CFR
10.20 and other applicable disclosure law. For more information about
FDA's posting of comments to public dockets, see 80 FR 56469, September
18, 2015, or access the information at: <a href="https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf">https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf</a>.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852, 240-402-7500.
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 the Office of
Communication, Outreach, and Development, Center for Biologics
Evaluation and Research, 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: Julia Beaver, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 22, Rm. 2100, Silver Spring, MD 20993-0002, 240-
402-0489; or Stephen Ripley, Center for Biologics Evaluation and
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg.
71, Rm 7268, Silver Spring, MD 20993-0002, 240-402-7911.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a final guidance for industry
entitled ``Nonmetastatic Castration-Resistant Prostate Cancer:
Considerations for Metastasis-Free Survival Endpoint in Clinical
Trials.'' Nonmetastatic castration-resistant prostate cancer (nmCRPC)
is defined by rising prostate-specific antigen (PSA) despite castrate
levels of testosterone and no radiographic evidence of distant
metastatic disease. Despite earlier detection of localized prostate
cancer and advances in surgical and radiation techniques, many patients
will continue to have rising PSA after local therapy (e.g., surgery,
radiation) for recurrent disease and subsequent androgen deprivation
therapy. Patients with nmCRPC can have a prolonged disease course
following the detection of a rising PSA until documentation of distant
metastases or death. Such a prolonged assessment period (in which
patients may receive multiple therapies) with low death rates may make
the use of overall survival impractical as a primary endpoint to
support approval of products in this disease setting.
These issues were discussed at an Oncologic Drugs Advisory
Committee meeting in 2011, during which the committee acknowledged that
endpoints that can be measured earlier in the course of disease, such
as metastasis-free survival, defined as the time from randomization to
distant radiographic disease or death, would be useful in assessing the
treatment effect of products in patients with nmCRPC. Additionally, the
Oncologic Drugs Advisory Committee noted that the transition from
nmCRPC to radiographically detectable metastatic disease (e.g., bone
disease or visceral disease) is a clinically relevant event that can be
associated with morbidity and the need for additional medical
interventions. Conversely, local progression events may be treated with
local therapies, may never progress to distant disease, and may not
lead to systemic morbidity. Thus, a large treatment effect on
metastasis-free survival with an acceptable safety profile could
demonstrate clinical benefit and support product approval.
This guidance finalizes the draft guidance of the same title issued
on November 14, 2018, (83 FR 56857). Changes from the draft to the
final include clarifying edits and expanding upon certain
recommendations in the draft guidance.
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 ``Nonmetastatic Castration-Resistant
Prostate Cancer: Considerations for Metastasis-Free Survival Endpoint
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
information are subject to review by OMB under the PRA. The collections
of information in 21 CFR part 312 have been approved under OMB control
number 0910-0014. The collections of information in 21 CFR parts 50 and
56 (Protection of Human Subjects and Institutional Review Boards) have
been approved under OMB control number 0910-0130.
III. Electronic Access
Persons with access to the internet may obtain the guidance at
either <a href="https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs">https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs</a>, <a href="https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics">https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics</a>, or
<a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Dated: August 2, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2021-16929 Filed 8-6-21; 8:45 am]
BILLING CODE 4164-01-P
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