[Federal Register Volume 83, Number 216 (Wednesday, November 7, 2018)]
[Notices]
[Pages 55722-55723]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[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Evaluate the Safety of Human Drugs or Biological Products; Draft 
Guidance for Industry; Availability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the availability of a draft guidance for industry entitled ``Meta-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of regulatory decision-making.\1\ This draft guidance is also intended 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DATES: Submit either electronic or written comments on the draft 
guidance by January 7, 2019 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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.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

[[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