[Federal Register Volume 80, Number 195 (Thursday, October 8, 2015)]
[Notices]
[Pages 60916-60917]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-25630]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2008-D-0449]


Integrated Summary of Effectiveness; Guidance for Industry; 
Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a guidance for industry entitled ``Integrated 
Summary of Effectiveness.'' This guidance describes how an integrated 
summary of effectiveness (ISE) should be prepared by industry for new 
drug applications (NDAs) and biologics license applications (BLAs). 
This guidance is intended to improve the quality of drug applications 
by describing what efficacy information should be submitted so that FDA 
can make a regulatory decision on an application. This guidance 
finalizes the draft guidance issued August 28, 2008.

DATES: Submit either electronic or written comments on Agency guidances 
at any time.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to http://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 http://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): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, 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-2008-D-0449 for Integrated Summary of Effectiveness; Guidance for 
Industry; Availability. Received comments will be placed in the docket 
and, except for those submitted as ``Confidential Submissions,'' 
publicly viewable at http://www.regulations.gov or at the Division of 
Dockets Management 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 http://www.regulations.gov. 
Submit both copies to the Division of Dockets Management. 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: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to http://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 Division of Dockets Management, 5630 Fishers 
Lane, Rm. 1061, Rockville, MD 20852.
    Submit written requests for single copies of this 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 the Office of 
Communication, Training, and Manufacturers Assistance, Center for 
Biologics Evaluation and Research, 10903 New Hampshire Ave., Bldg. 71, 
Rm. 3128, Silver Spring, MD 20993-0002. The guidance may also be 
obtained from the Center for Biologics Evaluation and Research by mail 
by calling 1-800-835-4709 or 240-402-7800. 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: Helen Sile, Center for Drug Evaluation 
and Research, Food and Drug Administration, 10903 New Hampshire Ave., 
Bldg. 22, Rm. 6462, Silver Spring, MD 20993-0002, 301-796-4123; 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 guidance for industry 
entitled ``Integrated Summary of Effectiveness.'' This guidance 
describes how an ISE should be prepared by industry for NDAs and BLAs. 
The ISE has been required as part of an NDA submission since 1985 (21 
CFR 314.50(d)(5)(v)), but the regulation does not describe the specific 
components of the ISE. The guidance for industry ``Guideline for the 
Format and Content of the Clinical and Statistical Sections of an 
Application'' (Clin-Stat guidance) provides a description of what FDA 
recommends for inclusion in an ISE. However, since the Clin-Stat 
guidance was published, several International Conference on 
Harmonisation guidances, including the ICH guidances for industry ``E3 
Structure and Content of Clinical Study Reports,'' ``E10 Choice of 
Control Group and Related Issues in Clinical Trials,'' and ``M4E The 
CTD--Efficacy,'' have

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provided additional recommendations for describing individual trials 
and providing results of efficacy analyses.
    This guidance supersedes section II.G., Integrated Summary of 
Effectiveness Data, of the Clin-Stat guidance to reflect FDA's current 
thinking regarding the format and content of the ISE to provide a truly 
integrated analysis, rather than a summary of efficacy results from 
individual clinical trials, and to satisfy FDA regulatory requirements. 
This guidance also incorporates the conceptual framework of section 
2.7.3, Summary of Clinical Efficacy, from ICH M4E. Although there are 
no corresponding regulations requiring an ISE for BLA submissions, 
applicants are encouraged to provide these analyses.
    The focus of the ISE is not on the detailed results of individual 
studies, which are described in individual study reports, but a 
comprehensive, detailed, integrated analysis that goes beyond 
individual study results to examine all sources of information 
concerning effectiveness to provide further insight into the efficacy 
of the study drug. Integrated analyses included in an ISE generally 
fall into two broad categories: (1) Comparing the individual studies to 
better understand the overall results; and (2) using the greater power 
of pooled analyses to gain insight into the nature of the drug's 
effectiveness in demographic (e.g., age, sex, race, and ethnicity) and 
other subpopulations, dose-response, and onset and duration of effect, 
among others.
    A draft of this guidance was published for comment in the Federal 
Register on August 28, 2008 (73 FR 50825). Comments received on the 
draft guidance have been considered and the guidance has been revised 
as follows: (1) Clarification on the difference between the document 
included in Module 2, section 2.7.3, Summary of Clinical Efficacy, from 
ICH M4E, and the ISE has been provided; (2) the definition of 
integrated analyses has been revised and the components that constitute 
an integrated analyses have been clarified; (3) pooled analyses has 
been defined; and (4) the recommendations for when it is appropriate to 
pool data has been included.
    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 preparing an ISE. 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. The 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 collections of information in 21 CFR part 314 have been 
approved under OMB control number 0910-0001. The collections of 
information for submission of data in a BLA under 21 CFR 601.2 have 
been approved under OMB control number 0910-0338.

III. Electronic Access

    Persons with access to the Internet may obtain the guidance at 
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or 
http://www.regulations.gov.

    Dated: October 2, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-25630 Filed 10-7-15; 8:45 am]
 BILLING CODE 4164-01-P