Notice2023-05910
Clinical Trial Considerations To Support Accelerated Approval of Oncology Therapeutics; Draft Guidance for Industry; Availability
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Published
March 27, 2023
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The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled "Clinical Trial Considerations to Support Accelerated Approval of Oncology Therapeutics." The purpose of this guidance is to provide recommendations to sponsors of anti-cancer drugs or biological products on considerations for designing trials intended to support accelerated approval. The accelerated approval pathway is commonly used for approval of oncology drugs due to the serious and life-threatening nature of cancer. Although single-arm trials have been commonly used to support accelerated approval, a randomized controlled trial is the preferred approach as it provides a more robust efficacy and safety assessment and allows for direct comparisons to an available therapy. This guidance describes considerations for designing, conducting, and analyzing data for trials intended to support accelerated approvals of oncology therapeutics.
Full Text
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<title>Federal Register, Volume 88 Issue 58 (Monday, March 27, 2023)</title>
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[Federal Register Volume 88, Number 58 (Monday, March 27, 2023)]
[Notices]
[Pages 18148-18149]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2023-05910]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2023-D-0110]
Clinical Trial Considerations To Support Accelerated Approval of
Oncology Therapeutics; Draft Guidance for Industry; Availability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the availability of a draft guidance for industry entitled ``Clinical
Trial Considerations to Support Accelerated Approval of Oncology
Therapeutics.'' The purpose of this guidance is to provide
recommendations to sponsors of anti-cancer drugs or biological products
on considerations for designing trials intended to support accelerated
approval. The accelerated approval pathway is commonly used for
approval of oncology drugs due to the serious and life-threatening
nature of cancer. Although single-arm trials have been commonly used to
support accelerated approval, a randomized controlled trial is the
preferred approach as it provides a more robust efficacy and safety
assessment and allows for direct comparisons to an available therapy.
This guidance describes considerations for designing, conducting, and
analyzing data for trials intended to support accelerated approvals of
oncology therapeutics.
DATES: Submit either electronic or written comments on the draft
guidance by May 26, 2023 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:
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-2023-D-0110 for ``Clinical Trial Considerations to Support
Accelerated Approval of Oncology Therapeutics.'' 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 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 the draft guidance to
the Division of Drug Information, Center for Drug Evaluation and
Research, Food
[[Page 18149]]
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, 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 draft guidance document.
FOR FURTHER INFORMATION CONTACT: Lola Fashoyin-Aje, Oncology Center of
Excellence, Center for Drug Evaluation and Research, Food and Drug
Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 2352, Silver
Spring, MD 20993, 240-402-0205; or Diane Maloney, Center for Biologics
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 71, Rm. 7242, Silver Spring, MD 20993, 240-402-
8113.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a draft guidance for industry
entitled ``Clinical Trial Considerations to Support Accelerated
Approval of Oncology Therapeutics.'' The purpose of this guidance is to
provide recommendations to sponsors of anti-cancer drugs or biological
products on considerations for designing trials intended to support
accelerated approval. The accelerated approval pathway is commonly used
for approval of oncology drugs in part due to the serious and life-
threatening nature of cancer and because of available surrogate or
intermediate clinical endpoints considered reasonably likely to predict
clinical benefit. Single-arm trial designs and response rate endpoints
(with duration of response as supportive) have most commonly been used
in oncology because response rate is a marker of drug activity since
malignant tumors do not typically regress on their own, and response
rate can be interpreted in single-arm trials for monotherapy drug
regimens. However, there are limitations to the use of single-arm
trials in support of accelerated approval, including but not limited
to: small safety datasets, low magnitude response rates that may not be
reasonably likely to predict clinical benefit, and the inability to
establish differential contribution of effect for combination regimens.
Additionally, the reliance on cross-trial comparisons to historical
trials to assess whether the observed treatment effect represents an
improvement over available therapy is challenging. These limitations
add uncertainty to the assessment of the safety and/or effectiveness of
a drug such that accelerated approval based on a single-arm trial may
not be justified in a given clinical setting.
Given the limitations of single-arm trials, FDA considers a
randomized controlled trial to be the most appropriate trial design to
support accelerated approval of oncology drugs. When properly designed
and executed, a randomized controlled trial provides a more robust
efficacy and safety assessment and allows for direct comparisons to a
concurrent control arm. Sponsors can, as appropriate, elect to conduct
a single randomized controlled trial to support an accelerated approval
and to verify clinical benefit (i.e., follow the ``one-trial''
approach), or they can conduct separate trials--one to support the
accelerated approval and another, a confirmatory trial, to verify
clinical benefit. The ``one-trial'' approach maintains efficiency in
drug development by providing early access to an investigational drug
using the accelerated approval pathway, while ensuring that a
postmarketing trial is fully accrued and well underway to verify longer
term benefit in a timely fashion.
This guidance describes considerations for designing, conducting,
and analyzing data for trials intended to support accelerated approval
of oncology drugs. Specifically, the guidance provides recommendations
addressing the design, conduct, and analyses of data for either two
separate randomized controlled trials or for using the ``one-trial''
approach for accelerated approval. The guidance also provides
recommendations for designing, conducting, and analyzing data from a
single-arm trial intended to support accelerated approval (when
appropriate), and the considerations for determining whether the data
may be adequate for this purpose. Regardless of the approach under
consideration, FDA recommends early discussion before study initiation
and during trials, as appropriate.
This draft guidance is being issued consistent with FDA's good
guidance practices regulation (21 CFR 10.115). The draft guidance, when
finalized, will represent the current thinking of FDA on ``Clinical
Trial Considerations to Support Accelerated Approval of Oncology
Therapeutics.'' 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 part 314
have been approved under OMB control number 0910-0001; and the
collections of information in 21 CFR part 601 have been approved under
OMB control number 0910-0338.
III. Electronic Access
Persons with access to the internet may obtain the guidance at
<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/biologics-guidances">https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances</a>,
<a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents">https://www.fda.gov/regulatory-information/search-fda-guidance-documents</a>, or <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Dated: March 17, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-05910 Filed 3-24-23; 8:45 am]
BILLING CODE 4164-01-P
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</html>Indexed from Federal Register on March 27, 2023.
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