Adjusting for Covariates in Randomized Clinical Trials for Drugs and Biologics With Continuous Outcomes; Draft Guidance for Industry; Availability, 17414-17415 [2019-08353]

Download as PDF 17414 Federal Register / Vol. 84, No. 80 / Thursday, April 25, 2019 / Notices 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. Send one self-addressed adhesive label to assist that office in processing your requests. See the SUPPLEMENTARY INFORMATION section for electronic access to the guidance document. FOR FURTHER INFORMATION CONTACT: Frederick Ensor, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 75, Rm. 6652, Silver Spring, MD 20993–0002, 240– 402–2733. SUPPLEMENTARY INFORMATION: khammond on DSKBBV9HB2PROD with NOTICES I. Background FDA is announcing the availability of a guidance for government public health and emergency response stakeholders entitled ‘‘Extending Expiration Dates of Doxycycline Tablets and Capsules in Strategic Stockpiles.’’ A number of government public health and emergency response stakeholders maintain stockpiles of doxycycline tablets or capsules for post-exposure prophylaxis (PEP) or treatment of inhalational anthrax in the event of an anthrax emergency. States have asked FDA what would be necessary to provide confidence that stockpiled doxycycline tablets and capsules have retained their original quality (i.e., purity and potency) beyond the manufacturer’s labeled expiration date so the replacement of stockpiled product could be deferred. This document provides guidance to government stakeholders on testing to extend the expiration date—under section 564A(b) of the FD&C Act (21 U.S.C. 360bbb–3a(b))—of stockpiled doxycycline tablets and capsules for public health emergency preparedness and response purposes for an anthrax emergency. This guidance applies to both doxycycline monohydrate and doxycycline hyclate tablets and capsules equivalent to 50 milligrams (mg) and 100 mg of doxycycline that are indicated for PEP or treatment of inhalational anthrax. Where doxycycline is mentioned throughout this guidance, it is meant to include both the hyclate and monohydrate forms of the drug that are indicated for PEP or treatment of inhalational anthrax. This guidance finalizes the draft guidance issued in April 2017. Those comments received on the draft guidance did not result in any policy changes but in some instances did result VerDate Sep<11>2014 16:25 Apr 24, 2019 Jkt 247001 in clarifying language in the final guidance document. This guidance is being issued consistent with FDA’s good guidance practices regulation (21 CFR 10.115). The guidance represents the current thinking of FDA on ‘‘Extending Expiration Dates of Doxycycline Tablets and Capsules in Strategic Stockpiles.’’ 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 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 collection of information has been approved under OMB control number 0910–0595. III. Electronic Access Persons with access to the internet may obtain the guidance at either https://www.fda.gov/Drugs/Guidance ComplianceRegulatoryInformation/ Guidances/default.htm or https:// www.regulations.gov. Dated: April 22, 2019. Lowell J. Schiller, Principal Associate Commissioner for Policy. [FR Doc. 2019–08349 Filed 4–24–19; 8:45 am] BILLING CODE 4164–01–P DEPARTMENT OF HEALTH AND HUMAN SERVICES randomized clinical trials with continuous endpoints. DATES: Submit either electronic or written comments on the draft guidance by June 24, 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 Food and Drug Administration [Docket No. FDA–2019–D–0934] Adjusting for Covariates in Randomized Clinical Trials for Drugs and Biologics With Continuous Outcomes; 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 Biologics with Continuous Outcomes.’’ The draft guidance, when finalized, will represent the current thinking of FDA on adjusting for covariates in randomized clinical trials for drugs and biologics, focusing on SUMMARY: PO 00000 Frm 00041 Fmt 4703 Sfmt 4703 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 Biologics with Continuous Outcomes.’’ Received comments will be placed in the docket and, except for those submitted as ‘‘Confidential Submissions,’’ publicly viewable at https://www.regulations.gov E:\FR\FM\25APN1.SGM 25APN1 khammond on DSKBBV9HB2PROD with NOTICES Federal Register / Vol. 84, No. 80 / Thursday, April 25, 2019 / Notices 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/201523389.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. 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 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 VerDate Sep<11>2014 16:25 Apr 24, 2019 Jkt 247001 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 Biologics with Continuous Outcomes.’’ This guidance provides recommendations for the use of analysis of covariance (ANCOVA) in randomized clinical trials. The target population for a new drug or biologic usually includes individuals with diverse prognostic factors, and the population studied in clinical trials should reflect this diversity. However, baseline differences in prognostic factors 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 guidance provides more detailed recommendations for the use of ANCOVA in randomized clinical trials. 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 ‘‘Adjusting for Covariates in Randomized Clinical Trials for Drugs and Biologics with Continuous Outcomes.’’ 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 PO 00000 Frm 00042 Fmt 4703 Sfmt 4703 17415 information found in FDA regulations. These collections of information 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 312.23 for investigational new drug application content and format 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 ComplianceRegulatoryInformation/ Guidances/default.htm, https:// www.fda.gov/BiologicsBloodVaccines/ GuidanceComplianceRegulatory Information/Guidances/default.htm, or https://www.regulations.gov. Dated: April 22, 2019. Lowell J. Schiller, Principal Associate Commissioner for Policy. [FR Doc. 2019–08353 Filed 4–24–19; 8:45 am] BILLING CODE 4164–01–P DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Center for Scientific Review; Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended, notice is hereby given of the following meetings. The meetings will be closed to the public in accordance with the provisions set forth in sections 552b(c)(4) and 552b(c)(6), Title 5 U.S.C., as amended. The grant applications and the discussions could disclose confidential trade secrets or commercial property such as patentable material, and personal information concerning individuals associated with the grant applications, the disclosure of which would constitute a clearly unwarranted invasion of personal privacy. Name of Committee: Center for Scientific Review Special Emphasis Panel; PAR Panel: Development of Appropriate Pediatric Formulations and Pediatric Drug Delivery Systems. Date: May 31, 2019. Time: 2:00 p.m. to 4:00 p.m. Agenda: To review and evaluate grant applications. Place: National Institutes of Health, 6701 Rockledge Drive, Bethesda, MD 20892 (Telephone Conference Call). Contact Person: Paek-Gyu Lee, Ph.D., Scientific Review Officer, Center for Scientific Review, National Institutes of Health, 6701 Rockledge Drive, Room 4201, MSC 7812, Bethesda, MD 20892, (301) 613– 2064, leepg@csr.nih.gov. E:\FR\FM\25APN1.SGM 25APN1

Agencies

[Federal Register Volume 84, Number 80 (Thursday, April 25, 2019)]
[Notices]
[Pages 17414-17415]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-08353]


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

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 Biologics With Continuous Outcomes; 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 Biologics 
with Continuous Outcomes.'' The draft guidance, when finalized, will 
represent the current thinking of FDA on adjusting for covariates in 
randomized clinical trials for drugs and biologics, focusing on 
randomized clinical trials with continuous endpoints.

DATES: Submit either electronic or written comments on the draft 
guidance by June 24, 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-2019-D-0934 for ``Adjusting for Covariates in Randomized Clinical 
Trials for Drugs and Biologics with Continuous Outcomes.'' Received 
comments will be placed in the docket and, except for those submitted 
as ``Confidential Submissions,'' publicly viewable at https://www.regulations.gov

[[Page 17415]]

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 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 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, 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 Biologics with Continuous Outcomes.'' This guidance provides 
recommendations for the use of analysis of covariance (ANCOVA) in 
randomized clinical trials.
    The target population for a new drug or biologic usually includes 
individuals with diverse prognostic factors, and the population studied 
in clinical trials should reflect this diversity. However, baseline 
differences in prognostic factors 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 
guidance provides more detailed recommendations for the use of ANCOVA 
in randomized clinical trials.
    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 ``Adjusting 
for Covariates in Randomized Clinical Trials for Drugs and Biologics 
with Continuous Outcomes.'' 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 found in FDA regulations. These collections of information 
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 312.23 for investigational new 
drug application content and format 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/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or 
https://www.regulations.gov.

    Dated: April 22, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-08353 Filed 4-24-19; 8:45 am]
BILLING CODE 4164-01-P