83 FR 55722 - Meta-Analyses of Randomized Controlled Clinical Trials To Evaluate the Safety of Human Drugs or Biological Products; Draft Guidance for Industry; Availability
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration Federal Register Volume 83, Issue 216 (November 7, 2018)
Food and Drug Administration
Federal Register Volume 83, Issue 216 (November 7, 2018)
| Page Range | 55722-55723 | |
| FR Document | 2018-24316 |
[Federal Register Volume 83, Number 216 (Wednesday, November 7, 2018)] [Notices] [Pages 55722-55723] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2018-24316] ----------------------------------------------------------------------- DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2018-D-3710] Meta-Analyses of Randomized Controlled Clinical Trials To Evaluate the Safety of Human Drugs or Biological Products; Draft Guidance for Industry; Availability AGENCY: Food and Drug Administration, HHS.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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled ``Meta- Analyses of Randomized Controlled Clinical Trials to Evaluate the Safety of Human Drugs or Biological Products.'' This document, when finalized, will provide guidance to applicants submitting investigational new drug applications, new drug applications, biologics license applications, or supplemental applications on the use of meta- analyses of randomized controlled clinical trials (RCTs) to evaluate the safety of human drugs or biological products within the framework of regulatory decision-making.\1\ This draft guidance is also intended for FDA reviewers and for third-party entities that prepare or evaluate meta-analyses assessing the safety of drug products. Specifically, this guidance describes the factors FDA intends to consider when evaluating the strength of evidence provided by a meta-analysis studying the safety of drugs. --------------------------------------------------------------------------- \1\ For the purposes of this guidance, all references to drugs include both human drugs and biologic products unless otherwise specified. DATES: Submit either electronic or written comments on the draft guidance by January 7, 2019 to ensure that the Agency considers your comment on this draft guidance before it begins work on the final --------------------------------------------------------------------------- version of the guidance.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:Federal eRulemaking Portal: https://www.regulations.gov. Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to https://www.regulations.gov will be posted to the docket unchanged. Because your comment will be made public, you are solely responsible for ensuring that your comment does not include any confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone else's Social Security number, or confidential business information, such as a manufacturing process. Please note that if you include your name, contact information, or other information that identifies you in the body of your comments, that information will be posted on https://www.regulations.gov. If you want to submit a comment with confidential information that you do not wish to be made available to the public, submit the comment as a written/paper submission and in the manner detailed (see ``Written/Paper Submissions'' and ``Instructions''). Written/Paper Submissions Submit written/paper submissions as follows: Mail/Hand Delivery/Courier (for written/paper submissions): Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. For written/paper comments submitted to the Dockets Management Staff, FDA will post your comment, as well as any attachments, except for information submitted, marked and identified, as confidential, if submitted as detailed in ``Instructions.'' Instructions: All submissions received must include the Docket No. FDA-2018-D-3710 for ``Meta-Analyses of Randomized Controlled Clinical Trials to Evaluate the Safety of Human Drugs or Biological Products: Draft Guidance for Industry; Availability.'' 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.thefederalregister.org/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 [[Page 55723]] Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. 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 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: Scott N. Goldie, Office of Biostatistics, Center for Drug Evaluation and Research, 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 draft guidance for industry entitled ``Meta-Analyses of Randomized Controlled Clinical Trials to Evaluate the Safety of Human Drugs or Biological Products.'' Evaluating the safety of drug products, both before approval and after marketing, is a fundamental responsibility of the FDA. This evaluation often requires combining and integrating information from multiple sources, and meta-analysis is a useful tool for this purpose. This draft guidance describes general principles of design, conduct, and reporting that FDA intends to apply to meta-analyses conducted by the Agency, and to use as benchmarks when evaluating meta- analyses conducted by sponsors or third parties. The focus of the draft guidance is on the evaluation of safety. This draft guidance is not intended to be a reference guide on how to conduct a meta-analysis. Rather, this draft guidance document discusses the important principles underlying best practices for safety meta-analyses and the way that FDA intends to factor adherence to those principles into its decision- making process. This draft guidance is being issued to fulfill a commitment made under the Prescription Drug User Fee V agreement (section IX.B.3 of the document entitled ``PDUFA Reauthorization Performance Goals and Procedures Fiscal Years 2013 through 2017'') to promote a better understanding and increased consistency among the Agency, industry and other stakeholders regarding meta-analyses and their role in regulatory decision-making. 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 ``Meta- Analyses of Randomized Controlled Clinical Trials to Evaluate the Safety of Human Drugs or Biological Products.'' 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. This guidance is not subject to Executive Order 12866. II. Paperwork Reduction Act of 1995 This draft guidance refers to previously approved collections of information that are subject to review by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501- 3520). The collections of information in 21 CFR parts 312, 314, and 601 have been approved under OMB control numbers 0910-0014, 0910-0001, and 0910-0338 respectively. III. Electronic Access Persons with access to the internet may obtain the draft guidance at either https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or https://www.regulations.gov. Dated: November 1, 2018. Leslie Kux, Associate Commissioner for Policy. [FR Doc. 2018-24316 Filed 11-6-18; 8:45 am] BILLING CODE 4164-01-P
![55722 Federal Register / Vol. 83, No. 216 / Wednesday, November 7, 2018 / Notices
TABLE 1—ESTIMATED ANNUAL REPORTING BURDEN 1—Continued
Number of Average
Number of Total annual
Information collection activity responses per burden per Total hours
respondents responses
respondent response
Total .............................................................................. ........................ ........................ ........................ ........................ 122
1 There are no capital costs or operating and maintenance costs associated with this collection of information.
We have increased our burden provided by a meta-analysis studying Instructions: All submissions received
estimate since last approval to account the safety of drugs. must include the Docket No. FDA–
for attestations added by FDARA; DATES: Submit either electronic or 2018–D–3710 for ‘‘Meta-Analyses of
however, all other information written comments on the draft guidance Randomized Controlled Clinical Trials
collection elements remain unchanged. by January 7, 2019 to ensure that the to Evaluate the Safety of Human Drugs
Dated: November 1, 2018. Agency considers your comment on this or Biological Products: Draft Guidance
draft guidance before it begins work on for Industry; Availability.’’ Received
Leslie Kux,
the final version of the guidance. comments will be placed in the docket
Associate Commissioner for Policy. and, except for those submitted as
[FR Doc. 2018–24320 Filed 11–6–18; 8:45 am] ADDRESSES: You may submit comments
‘‘Confidential Submissions,’’ publicly
BILLING CODE 4164–01–P on any guidance at any time as follows: viewable at https://www.regulations.gov
Electronic Submissions or at the Dockets Management Staff
between 9 a.m. and 4 p.m., Monday
DEPARTMENT OF HEALTH AND Submit electronic comments in the through Friday.
HUMAN SERVICES following way: • Confidential Submissions—To
• Federal eRulemaking Portal: submit a comment with confidential
Food and Drug Administration https://www.regulations.gov. Follow the information that you do not wish to be
instructions for submitting comments. made publicly available, submit your
[Docket No. FDA–2018–D–3710] Comments submitted electronically, comments only as a written/paper
including attachments, to https:// submission. You should submit two
Meta-Analyses of Randomized www.regulations.gov will be posted to copies total. One copy will include the
Controlled Clinical Trials To Evaluate the docket unchanged. Because your information you claim to be confidential
the Safety of Human Drugs or comment will be made public, you are with a heading or cover note that states
Biological Products; Draft Guidance solely responsible for ensuring that your ‘‘THIS DOCUMENT CONTAINS
for Industry; Availability comment does not include any CONFIDENTIAL INFORMATION.’’ The
confidential information that you or a Agency will review this copy, including
AGENCY: Food and Drug Administration, third party may not wish to be posted, the claimed confidential information, in
HHS. such as medical information, your or its consideration of comments. The
ACTION: Notice of availability. anyone else’s Social Security number, or second copy, which will have the
confidential business information, such claimed confidential information
SUMMARY: The Food and Drug as a manufacturing process. Please note redacted/blacked out, will be available
Administration (FDA or Agency) is that if you include your name, contact for public viewing and posted on
announcing the availability of a draft information, or other information that https://www.regulations.gov. Submit
guidance for industry entitled ‘‘Meta- identifies you in the body of your both copies to the Dockets Management
Analyses of Randomized Controlled comments, that information will be Staff. If you do not wish your name and
Clinical Trials to Evaluate the Safety of posted on https://www.regulations.gov. contact information to be made publicly
Human Drugs or Biological Products.’’ • If you want to submit a comment available, you can provide this
This document, when finalized, will with confidential information that you information on the cover sheet and not
provide guidance to applicants do not wish to be made available to the in the body of your comments and you
submitting investigational new drug public, submit the comment as a must identify this information as
applications, new drug applications, written/paper submission and in the ‘‘confidential.’’ Any information marked
biologics license applications, or manner detailed (see ‘‘Written/Paper as ‘‘confidential’’ will not be disclosed
supplemental applications on the use of Submissions’’ and ‘‘Instructions’’). except in accordance with 21 CFR 10.20
meta-analyses of randomized controlled Written/Paper Submissions and other applicable disclosure law. For
clinical trials (RCTs) to evaluate the more information about FDA’s posting
safety of human drugs or biological Submit written/paper submissions as of comments to public dockets, see 80
products within the framework of follows: FR 56469, September 18, 2015, or access
regulatory decision-making.1 This draft • Mail/Hand Delivery/Courier (for the information at: https://www.gpo.gov/
guidance is also intended for FDA written/paper submissions): Dockets fdsys/pkg/FR-2015-09-18/pdf/2015-
reviewers and for third-party entities Management Staff (HFA–305), Food and 23389.pdf.
that prepare or evaluate meta-analyses Drug Administration, 5630 Fishers Docket: For access to the docket to
assessing the safety of drug products. Lane, Rm. 1061, Rockville, MD 20852. read background documents or the
amozie on DSK3GDR082PROD with NOTICES1
Specifically, this guidance describes the • For written/paper comments electronic and written/paper comments
factors FDA intends to consider when submitted to the Dockets Management received, go to https://
evaluating the strength of evidence Staff, FDA will post your comment, as www.regulations.gov and insert the
well as any attachments, except for docket number, found in brackets in the
1 For the purposes of this guidance, all references information submitted, marked and heading of this document, into the
to drugs include both human drugs and biologic identified, as confidential, if submitted ‘‘Search’’ box and follow the prompts
products unless otherwise specified. as detailed in ‘‘Instructions.’’ and/or go to the Dockets Management
VerDate Sep<11>2014 17:46 Nov 06, 2018 Jkt 247001 PO 00000 Frm 00035 Fmt 4703 Sfmt 4703 E:\FR\FM\07NON1.SGM 07NON1](https://thefederalregister.org/doc/83_FR_55938/page/1.svg)
![Federal Register / Vol. 83, No. 216 / Wednesday, November 7, 2018 / Notices 55723
Staff, 5630 Fishers Lane, Rm. 1061, adherence to those principles into its DEPARTMENT OF HEALTH AND
Rockville, MD 20852. decision-making process. HUMAN SERVICES
You may submit comments on any This draft guidance is being issued to
guidance at any time (see 21 CFR Food and Drug Administration
fulfill a commitment made under the
10.115(g)(5)). Submit written requests Prescription Drug User Fee V agreement [Docket No. FDA–2018–N–3758]
for single copies of the draft guidance to (section IX.B.3 of the document entitled
the Division of Drug Information, Center ‘‘PDUFA Reauthorization Performance Agency Information Collection
for Drug Evaluation and Research, Food Activities; Proposed Collection;
Goals and Procedures Fiscal Years 2013
and Drug Administration, 10001 New Comment Request; Individual Patient
through 2017’’) to promote a better
Hampshire Ave., Hillandale Building, Expanded Access Applications: Form
understanding and increased FDA 3926
4th Floor, Silver Spring, MD 20993–
consistency among the Agency, industry
0002; or to the Office of AGENCY: Food and Drug Administration,
and other stakeholders regarding meta-
Communication, Outreach, and HHS.
Development, Center for Biologics analyses and their role in regulatory
decision-making. ACTION: Notice.
Evaluation and Research, Food and
Drug Administration, 10903 New This draft guidance is being issued SUMMARY: The Food and Drug
Hampshire Ave., Bldg. 71, Rm. 3128, consistent with FDA’s good guidance Administration (FDA, Agency, or we) is
Silver Spring, MD 20993–0002. Send practices regulation (21 CFR 10.115). announcing an opportunity for public
one self-addressed adhesive label to The draft guidance, when finalized, will comment on the proposed collection of
assist that office in processing your represent the current thinking of FDA certain information by the Agency.
requests. See the SUPPLEMENTARY on ‘‘Meta-Analyses of Randomized Under the Paperwork Reduction Act of
INFORMATION section for electronic Controlled Clinical Trials to Evaluate 1995 (PRA), Federal Agencies are
access to the draft guidance document. the Safety of Human Drugs or Biological required to publish notice in the
FOR FURTHER INFORMATION CONTACT: Products.’’ It does not establish any Federal Register concerning each
Scott N. Goldie, Office of Biostatistics, rights for any person and is not binding proposed collection of information,
Center for Drug Evaluation and on FDA or the public. You can use an including each proposed extension of an
Research, Food and Drug alternative approach if it satisfies the existing collection of information, and
Administration, 10903 New Hampshire requirements of the applicable statutes to allow 60 days for public comment in
Ave., Bldg. 21, Rm. 3557, Silver Spring, and regulations. This guidance is not response to the notice. This notice
MD 20993–0002, 301–796–2055; or subject to Executive Order 12866. solicits comments on individual patient
Stephen Ripley, Center for Biologics expanded access applications.
Evaluation and Research, Food and II. Paperwork Reduction Act of 1995 DATES: Submit either electronic or
Drug Administration, 10903 New written comments on the collection of
This draft guidance refers to information by January 7, 2019.
Hampshire Ave., Bldg. 71, Rm. 7301,
previously approved collections of
Silver Spring, MD 20993–0002, 240– ADDRESSES: You may submit comments
information that are subject to review by as follows. Please note that late,
402–7911.
the Office of Management and Budget untimely filed comments will not be
SUPPLEMENTARY INFORMATION: (OMB) under the Paperwork Reduction considered. Electronic comments must
I. Background Act of 1995 (44 U.S.C. 3501–3520). The be submitted on or before January 7,
collections of information in 21 CFR 2019. The https://www.regulations.gov
FDA is announcing the availability of parts 312, 314, and 601 have been electronic filing system will accept
a draft guidance for industry entitled approved under OMB control numbers comments until 11:59 p.m. Eastern Time
‘‘Meta-Analyses of Randomized 0910–0014, 0910–0001, and 0910–0338 at the end of January 7, 2019. Comments
Controlled Clinical Trials to Evaluate respectively. received by mail/hand delivery/courier
the Safety of Human Drugs or Biological
(for written/paper submissions) will be
Products.’’ Evaluating the safety of drug III. Electronic Access
considered timely if they are
products, both before approval and after
Persons with access to the internet postmarked or the delivery service
marketing, is a fundamental
may obtain the draft guidance at either acceptance receipt is on or before that
responsibility of the FDA. This
https://www.fda.gov/Drugs/Guidance date.
evaluation often requires combining and
integrating information from multiple ComplianceRegulatoryInformation/ Electronic Submissions
sources, and meta-analysis is a useful Guidances/default.htm, https:// Submit electronic comments in the
tool for this purpose. www.fda.gov/BiologicsBloodVaccines/ following way:
This draft guidance describes general GuidanceComplianceRegulatory • Federal eRulemaking Portal:
principles of design, conduct, and Information/Guidances/default.htm, or https://www.regulations.gov. Follow the
reporting that FDA intends to apply to https://www.regulations.gov. instructions for submitting comments.
meta-analyses conducted by the Agency, Dated: November 1, 2018. Comments submitted electronically,
and to use as benchmarks when Leslie Kux, including attachments, to https://
evaluating meta-analyses conducted by www.regulations.gov will be posted to
Associate Commissioner for Policy.
sponsors or third parties. The focus of the docket unchanged. Because your
[FR Doc. 2018–24316 Filed 11–6–18; 8:45 am]
the draft guidance is on the evaluation comment will be made public, you are
amozie on DSK3GDR082PROD with NOTICES1
of safety. This draft guidance is not BILLING CODE 4164–01–P solely responsible for ensuring that your
intended to be a reference guide on how comment does not include any
to conduct a meta-analysis. Rather, this confidential information that you or a
draft guidance document discusses the third party may not wish to be posted,
important principles underlying best such as medical information, your or
practices for safety meta-analyses and anyone else’s Social Security number, or
the way that FDA intends to factor confidential business information, such
VerDate Sep<11>2014 17:46 Nov 06, 2018 Jkt 247001 PO 00000 Frm 00036 Fmt 4703 Sfmt 4703 E:\FR\FM\07NON1.SGM 07NON1](https://thefederalregister.org/doc/83_FR_55938/page/2.svg)
Document Created: 2018-11-07 00:04:55
Document Modified: 2018-11-07 00:04:55
| Category | Regulatory Information | |
| Collection | Federal Register | |
| sudoc Class | AE 2.7: GS 4.107: AE 2.106: | |
| Publisher | Office of the Federal Register, National Archives and Records Administration | |
| Section | Notices | |
| Action | Notice of availability. | |
| Dates | Submit either electronic or written comments on the draft guidance by January 7, 2019 to ensure that the Agency considers your comment on this draft guidance before it begins work on the final | |
| Contact | Scott N. Goldie, Office of Biostatistics, Center for Drug Evaluation and Research, 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. | |
| FR Citation | 83 FR 55722 |
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