[Federal Register Volume 89, Number 56 (Thursday, March 21, 2024)]
[Notices]
[Pages 20207-20209]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-05969]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2023-D-5470]


Real-World Evidence: Considerations Regarding Non-Interventional 
Studies for Drug and Biological Products; Draft Guidance for Industry; 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the availability of a draft guidance for industry entitled ``Real-World 
Evidence: Considerations Regarding Non-Interventional Studies for Drug 
and Biological Products.'' FDA is issuing this draft guidance as part 
of a series of guidance documents under its Real-World Evidence (RWE) 
Program and to satisfy, in part, a mandate under the Federal Food, 
Drug, and Cosmetic Act (FD&C Act) to issue guidance about the use of 
RWE in regulatory decision-making. The draft guidance provides 
recommendations to sponsors who are considering submitting a non-
interventional study, also referred to as an observational study, to 
FDA to contribute to a demonstration of substantial evidence of 
effectiveness and/or evidence of safety of a drug. This draft guidance 
was developed in response to stakeholders' growing interest in the 
potential use of non-interventional studies to contribute to a 
demonstration of the effectiveness or safety of a drug.

DATES: Submit either electronic or written comments on the draft 
guidance by June 18, 2024 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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

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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-5470 for ``Real-World Evidence: Considerations Regarding 
Non-Interventional Studies for Drug and Biological Products.'' 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 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: Dianne Paraoan, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 3326, Silver Spring, MD 20993-0002, 301-
796-3161, [email protected]; or James Myers, 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 ``Real-World Evidence: Considerations Regarding Non-
Interventional Studies for Drug and Biological Products.'' This draft 
guidance discusses attributes regarding the design and analysis of a 
non-interventional study that sponsors should consider when proposing 
such a study to contribute to a demonstration of substantial evidence 
of effectiveness and/or evidence of safety of a product. Examples of 
non-interventional study designs for evaluating the effectiveness and/
or safety of a drug include, but are not limited to, cohort studies, 
case-control studies, and self-controlled studies.
    Identifying and addressing the presence of confounding and other 
forms of bias is critical when planning and conducting non-
interventional studies. Before choosing a non-interventional study 
design for a study intended to support regulatory decisions regarding 
the safety and effectiveness of a drug, sponsors should consider how 
likely it is that such a study design and its conduct will be able to 
distinguish a true treatment effect from other influences. The draft 
guidance assists sponsors in identifying and addressing commonly 
encountered challenges when considering the use of a non-interventional 
study to contribute to a demonstration of substantial evidence of 
effectiveness and/or evidence of safety of a drug, including topics 
sponsors should consider before developing a prespecified protocol and 
statistical analysis plan. This draft guidance discusses the following 
major topics: (1) summary of the proposed approach, (2) study design, 
(3) data sources, and (4) analytical approach. The topics in this draft 
guidance should be considered in conjunction with the recommendations 
in other published guidances under the RWE Program.
    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 ``Real-World 
Evidence: Considerations Regarding Non-Interventional Studies for Drug 
and 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.

II. Paperwork Reduction Act of 1995

    While this guidance contains no collection of information, it does 
refer to previously approved FDA collections of information. The 
previously approved collections of information are subject to review by 
the Office of Management and Budget (OMB) under the Paperwork Reduction 
Act of 1995 (PRA) (44 U.S.C. 3501-3521). The collections of information 
in 21 CFR part 312 (investigational new drug applications) have been 
approved under OMB control number 0910-0014; the collections of 
information in 21 CFR part 314 (new drug marketing applications) have 
been approved under OMB control number 0910-0001; and the collections 
of information in 21 CFR part 601 (biologic license applications) have 
been approved under OMB control number 0910-0338. The collections of 
information in 21 CFR part 11 (electronic records and signatures) have 
been approved under OMB control number 0910-0303. 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 draft guidance 
at https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/

[[Page 20209]]

vaccines-blood-biologics/guidance-compliance-regulatory-information-
biologics/biologics-guidances, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, or https://www.regulations.gov.

    Dated: March 15, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2024-05969 Filed 3-20-24; 8:45 am]
BILLING CODE 4164-01-P