[Federal Register Volume 82, Number 209 (Tuesday, October 31, 2017)]
[Notices]
[Pages 50433-50434]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-23613]


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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2017-D-6113]


E9(R1) Statistical Principles for Clinical Trials: Addendum: 
Estimands and Sensitivity Analysis in Clinical Trials; International 
Council for Harmonisation; Draft Guidance for Industry; Availability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the availability of a draft guidance entitled ``E9(R1) Statistical 
Principles for Clinical Trials: Addendum: Estimands and Sensitivity 
Analysis in Clinical Trials.'' The draft guidance was prepared under 
the auspices of the International Council for Harmonisation (ICH), 
formerly the International Conference on Harmonisation. The draft 
guidance clarifies, updates, and extends the earlier ``E9 Statistical 
Principles for Clinical Trials'' in two main areas. Concerning 
estimands, it provides a framework for discussion of how the aims of a 
trial relate to the proposed statistical analysis. Concerning 
sensitivity analysis, it discusses how to use additional analyses to 
address concerns about the validity of assumptions underlying the main 
analysis. The draft guidance is intended to better align the choice of 
statistical methods with questions of regulatory importance and to 
improve the reliability of decisions about and representations of the 
effects of medical products.

DATES: Submit either electronic or written comments on the draft 
guidance by April 30, 2018 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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-2017-D-6113 for ``E9(R1) Statistical Principles for Clinical 
Trials: Addendum: Estimands and Sensitivity Analysis in Clinical 
Trials; International Council for Harmonisation; 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 office 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

[[Page 50434]]

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 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, 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. The guidance may also be obtained by mail by calling 
CBER at 1-800-835-4709 or 240-402-8010. See the SUPPLEMENTARY 
INFORMATION section for electronic access to the guidance document.

FOR FURTHER INFORMATION CONTACT:
    Regarding the guidance: Thomas Permutt, Center for Drug Evaluation 
and Research, Food and Drug Administration, 10903 New Hampshire Ave., 
Bldg. 21, Rm. 3614, Silver Spring, MD 20993-0002, 301-796-1271; or John 
Scott, Center for Biologics Evaluation and Research, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 1018, Silver 
Spring, MD 20993-0002, 240-402-8779.
    Regarding the ICH: Amanda Roache, Center for Drug Evaluation and 
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 
51, Rm. 1176, Silver Spring, MD 20993-0002, 301-796-4548.

SUPPLEMENTARY INFORMATION:

I. Background

    In recent years, regulatory authorities and industry associations 
from around the world have participated in many important initiatives 
to promote international harmonization of regulatory requirements under 
the ICH. FDA has participated in several ICH meetings designed to 
enhance harmonization, and FDA is committed to seeking scientifically 
based harmonized technical procedures for pharmaceutical development. 
One of the goals of harmonization is to identify and reduce differences 
in technical requirements for drug development among regulatory 
agencies.
    ICH was established to provide an opportunity for harmonization 
initiatives to be developed with input from both regulatory and 
industry representatives. FDA also seeks input from consumer 
representatives and others. ICH is concerned with harmonization of 
technical requirements for the registration of pharmaceutical products 
for human use among regulators around the world. The six founding 
members of the ICH are the European Commission; the European Federation 
of Pharmaceutical Industries Associations; FDA; the Japanese Ministry 
of Health, Labour, and Welfare; the Japanese Pharmaceutical 
Manufacturers Association; and the Pharmaceutical Research and 
Manufacturers of America. The Standing Members of the ICH Association 
include Health Canada and Swissmedic. Any party eligible as a Member in 
accordance with the ICH Articles of Association can apply for 
membership in writing to the ICH Secretariat. The ICH Secretariat, 
which coordinates the preparation of documentation, operates as an 
international nonprofit organization and is funded by the Members of 
the ICH Association.
    The ICH Assembly is the overarching body of the Association and 
includes representatives from each of the ICH members and observers. 
The Assembly is responsible for the endorsement of draft guidelines and 
adoption of final guidelines. FDA publishes ICH guidelines as FDA 
guidance.
    In July 2017, the ICH Assembly endorsed the draft guideline 
entitled ``E9(R1) Statistical Principles for Clinical Trials: Addendum: 
Estimands and Sensitivity Analysis in Clinical Trials'' and agreed that 
the guidance should be made available for public comment. The draft 
guidance is the product of the Efficacy Expert Working Group of the 
ICH. Comments about this draft will be considered by FDA and the 
Efficacy Expert Working Group.
    The draft guidance provides guidance on aligning the choice of 
statistical methods with the goals of a clinical trial; on 
communicating the rationale for such choices to FDA; and on using 
sensitivity analysis to characterize the robustness of the conclusions 
to plausible deviations from the assumptions of the main analysis.
    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 ``E9(R1) 
Statistical Principles for Clinical Trials: Addendum: Estimands and 
Sensitivity Analysis in Clinical Trials.'' 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. Electronic Access

    Persons with access to the internet may obtain the document at 
https://www.regulations.gov, https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or 
https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.

    Dated: October 26, 2017.
Anna K. Abram,
Deputy Commissioner for Policy, Planning, Legislation, and Analysis.
[FR Doc. 2017-23613 Filed 10-30-17; 8:45 am]
BILLING CODE 4164-01-P


