Adjusting for Covariates in Randomized Clinical Trials for Drugs and Biological Products; Draft Guidance for Industry; Availability, 27627-27629 [2021-10760]

Download as PDF jbell on DSKJLSW7X2PROD with NOTICES Federal Register / Vol. 86, No. 97 / Friday, May 21, 2021 / Notices Public Docket; Request for Comments.’’ Received comments, those filed in a timely manner (see ADDRESSES), 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.’’ FDA 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 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 the 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-201509-18/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. FOR FURTHER INFORMATION CONTACT: Joyce Yu, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave, Bldg. 31, Rm. 2417, Silver Spring, MD 20993–0002, 301–837–7126, Fax: 301–847–8533, email: CRDAC@ fda.hhs.gov, or FDA Advisory Committee Information Line, 1–800– 741–8138 (301–443–0572 in the Washington, DC area). A notice in the VerDate Sep<11>2014 17:15 May 20, 2021 Jkt 253001 Federal Register about last-minute modifications that impact a previously announced advisory committee meeting cannot always be published quickly enough to provide timely notice. Therefore, you should always check FDA’s website at https://www.fda.gov/ AdvisoryCommittees/default.htm and scroll down to the appropriate advisory committee meeting link, or call the advisory committee information line to learn about possible modifications before coming to the meeting. SUPPLEMENTARY INFORMATION: Agenda: The meeting presentations will be heard, viewed, captioned, and recorded through an online teleconferencing platform. The committee will discuss new drug application 213805, for the hypoxia inducible factor prolyl hydroxylase inhibitor, roxadustat tablets, submitted by FibroGen, Inc., for the treatment of anemia due to chronic kidney disease in adult patients not on dialysis and on dialysis. FDA intends to make background material available to the public no later than 2 business days before the meeting. If FDA is unable to post the background material on its website prior to the meeting, the background material will be made publicly available on FDA’s website at the time of the advisory committee meeting. Background material and the link to the online teleconference meeting room will be available at https://www.fda.gov/ AdvisoryCommittees/Calendar/ default.htm. Scroll down to the appropriate advisory committee meeting link. The meeting will include slide presentations with audio components to allow the presentation of materials in a manner that most closely resembles an in-person advisory committee meeting. Procedure: Interested persons may present data, information, or views, orally or in writing, on issues pending before the committee. All electronic and written submissions submitted to the Docket (see ADDRESSES) on or before June 30, 2021, will be provided to the committee. Oral presentations from the public will be scheduled between approximately 2:30 p.m. and 3:30 p.m. Eastern Time. Those individuals interested in making formal oral presentations should notify the contact person and submit a brief statement of the general nature of the evidence or arguments they wish to present, the names and addresses of proposed participants, and an indication of the approximate time requested to make their presentation on or before June 22, 2021. Time allotted for each presentation may be limited. If the PO 00000 Frm 00076 Fmt 4703 Sfmt 4703 27627 number of registrants requesting to speak is greater than can be reasonably accommodated during the scheduled open public hearing session, FDA may conduct a lottery to determine the speakers for the scheduled open public hearing session. The contact person will notify interested persons regarding their request to speak by June 23, 2021. For press inquiries, please contact the Office of Media Affairs at fdaoma@ fda.hhs.gov or 301–796–4540. FDA welcomes the attendance of the public at its advisory committee meetings and will make every effort to accommodate persons with disabilities. If you require accommodations due to a disability, please contact Joyce Yu (see FOR FURTHER INFORMATION CONTACT) at least 7 days in advance of the meeting. FDA is committed to the orderly conduct of its advisory committee meetings. Please visit our website at https://www.fda.gov/Advisory Committees/AboutAdvisoryCommittees/ ucm111462.htm for procedures on public conduct during advisory committee meetings. Notice of this meeting is given under the Federal Advisory Committee Act (5 U.S.C. app. 2). Dated: May 14, 2021. Lauren K. Roth, Acting Principal Associate Commissioner for Policy. [FR Doc. 2021–10751 Filed 5–20–21; 8:45 am] BILLING CODE 4164–01–P DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA–2019–D–0934] Adjusting for Covariates in Randomized Clinical Trials for Drugs and Biological Products; Draft Guidance for Industry; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice of availability. The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled ‘‘Adjusting for Covariates in Randomized Clinical Trials for Drugs and Biological Products.’’ The draft guidance, when finalized, will represent the current thinking of FDA on adjusting for covariates in randomized clinical trials for drugs and biologics. This draft guidance revises the draft guidance ‘‘Adjusting for Covariates in Randomized Clinical Trials for Drugs and Biologics with Continuous SUMMARY: E:\FR\FM\21MYN1.SGM 21MYN1 27628 Federal Register / Vol. 86, No. 97 / Friday, May 21, 2021 / Notices Outcomes’’ that published April 25, 2019. This revision provides more detailed recommendations for the use of linear models for covariate adjustment and also includes recommendations for covariate adjustment using nonlinear models. Submit either electronic or written comments on the draft guidance by July 20, 2021 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: DATES: 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’’). jbell on DSKJLSW7X2PROD with NOTICES 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– 2019–D–0934 for ‘‘Adjusting for Covariates in Randomized Clinical Trials for Drugs and Biological VerDate Sep<11>2014 17:15 May 20, 2021 Jkt 253001 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-201509-18/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 (CBER), Food PO 00000 Frm 00077 Fmt 4703 Sfmt 4703 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, Center for Drug Evaluation and Research, Office of Biostatistics, 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 ‘‘Adjusting for Covariates in Randomized Clinical Trials for Drugs and Biological Products.’’ The target population for a new drug or biological product usually includes individuals with diverse prognostic factors, and the population studied in clinical trials should reflect this diversity. However, baseline differences in prognostic factors may impair the detection and estimation of treatment effects. Incorporating prognostic factors in the statistical analysis of clinical trial data can mitigate this impairment and can result in a more efficient use of data to demonstrate and quantify the effects of treatment. The International Council for Harmonisation guidance for industry entitled ‘‘E9 Statistical Principles for Clinical Trials’’ briefly addresses these issues (https://www.fda.gov/downloads/ drugs/guidancecomplianceregulatory information/guidances/ucm073137.pdf). This draft guidance provides more detailed recommendations for the use of covariate adjustment in randomized clinical trials. This draft guidance revises the draft guidance ‘‘Adjusting for Covariates in Randomized Clinical Trials for Drugs and Biologics with Continuous Outcomes’’ that published April 25, 2019. Compared with the April 2019 draft guidance, this draft guidance provides more detailed recommendations and discusses use of nonlinear models in addition to linear models. This draft guidance is being issued consistent with FDA’s good guidance practices regulation (21 CFR 10.115). The draft guidance, when finalized, will E:\FR\FM\21MYN1.SGM 21MYN1 Federal Register / Vol. 86, No. 97 / Friday, May 21, 2021 / Notices represent the current thinking of FDA on ‘‘Adjusting for Covariates in Randomized Clinical Trials for Drugs and Biologics.’’ 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 draft 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 312.23 for the content and format of investigational new drug applications have been approved under OMB control number 0910–0014. III. Electronic Access Persons with access to the internet may obtain the draft guidance at https:// www.fda.gov/drugs/guidancecompliance-regulatory-information/ guidances-drugs, https://www.fda.gov/ vaccines-blood-biologics/guidancecompliance-regulatory-informationbiologics/biologics-guidances, or https:// www.regulations.gov. Dated: May 18, 2021. Lauren K. Roth, Acting Principal Associate Commissioner for Policy. [FR Doc. 2021–10760 Filed 5–20–21; 8:45 am] BILLING CODE 4164–01–P DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA–2016–D–0199] Enforcement Policy Regarding Use of National Health Related Item Code and National Drug Code Numbers on Device Labels and Packages; Guidance for Industry and Food and Drug Administration Staff; Availability AGENCY: Food and Drug Administration, HHS. jbell on DSKJLSW7X2PROD with NOTICES ACTION: Notice of availability. The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance entitled ‘‘Enforcement Policy Regarding Use of National Health Related Item Code and National Drug SUMMARY: VerDate Sep<11>2014 17:15 May 20, 2021 Jkt 253001 Code Numbers on Device Labels and Packages.’’ This guidance describes the Agency’s policy regarding the prohibition against providing National Health Related Item Code (NHRIC) and National Drug Code (NDC) numbers on device labels and device packages set forth in FDA regulations. As described in the guidance, FDA does not intend to object to the use of FDA legacy identification numbers on device labels and packages for finished devices manufactured and labeled prior to September 24, 2023. The guidance is immediately in effect, but it remains subject to comment in accordance with the Agency’s good guidance practices. DATES: The announcement of the guidance is published in the Federal Register on May 21, 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: • 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 PO 00000 Frm 00078 Fmt 4703 Sfmt 4703 27629 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– 2016–D–0199 for ‘‘Enforcement Policy Regarding Use of National Health Related Item Code and National Drug Code Numbers on Device Labels and Packages; Guidance for Industry and Food and Drug Administration Staff.’’ 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-201509-18/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. E:\FR\FM\21MYN1.SGM 21MYN1

Agencies

[Federal Register Volume 86, Number 97 (Friday, May 21, 2021)]
[Notices]
[Pages 27627-27629]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-10760]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2019-D-0934]


Adjusting for Covariates in Randomized Clinical Trials for Drugs 
and 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 ``Adjusting 
for Covariates in Randomized Clinical Trials for Drugs and Biological 
Products.'' The draft guidance, when finalized, will represent the 
current thinking of FDA on adjusting for covariates in randomized 
clinical trials for drugs and biologics. This draft guidance revises 
the draft guidance ``Adjusting for Covariates in Randomized Clinical 
Trials for Drugs and Biologics with Continuous

[[Page 27628]]

Outcomes'' that published April 25, 2019. This revision provides more 
detailed recommendations for the use of linear models for covariate 
adjustment and also includes recommendations for covariate adjustment 
using nonlinear models.

DATES: Submit either electronic or written comments on the draft 
guidance by July 20, 2021 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-2019-D-0934 for ``Adjusting for Covariates in Randomized Clinical 
Trials for Drugs 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 (CBER), 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, Center for Drug 
Evaluation and Research, Office of Biostatistics, 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 ``Adjusting for Covariates in Randomized Clinical Trials for 
Drugs and Biological Products.'' The target population for a new drug 
or biological product usually includes individuals with diverse 
prognostic factors, and the population studied in clinical trials 
should reflect this diversity. However, baseline differences in 
prognostic factors may impair the detection and estimation of treatment 
effects. Incorporating prognostic factors in the statistical analysis 
of clinical trial data can mitigate this impairment and can result in a 
more efficient use of data to demonstrate and quantify the effects of 
treatment. The International Council for Harmonisation guidance for 
industry entitled ``E9 Statistical Principles for Clinical Trials'' 
briefly addresses these issues (https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm073137.pdf). This 
draft guidance provides more detailed recommendations for the use of 
covariate adjustment in randomized clinical trials.
    This draft guidance revises the draft guidance ``Adjusting for 
Covariates in Randomized Clinical Trials for Drugs and Biologics with 
Continuous Outcomes'' that published April 25, 2019. Compared with the 
April 2019 draft guidance, this draft guidance provides more detailed 
recommendations and discusses use of nonlinear models in addition to 
linear models.
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will

[[Page 27629]]

represent the current thinking of FDA on ``Adjusting for Covariates in 
Randomized Clinical Trials for Drugs and Biologics.'' 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 draft 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 312.23 for the content and format of 
investigational new drug applications have been approved under OMB 
control number 0910-0014.

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

    Dated: May 18, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2021-10760 Filed 5-20-21; 8:45 am]
BILLING CODE 4164-01-P
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