82 FR 50433 - E9(R1) Statistical Principles for Clinical Trials: Addendum: Estimands and Sensitivity Analysis in Clinical Trials; International Council for Harmonisation; Draft Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 82, Issue 209 (October 31, 2017)

Page Range		50433-50434
FR Document		2017-23613

The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance entitled ``E9(R1) Statistical Principles for Clinical Trials: Addendum: Estimands and Sensitivity Analysis in Clinical Trials.'' The draft guidance was prepared under the auspices of the International Council for Harmonisation (ICH), formerly the International Conference on Harmonisation. The draft guidance clarifies, updates, and extends the earlier ``E9 Statistical Principles for Clinical Trials'' in two main areas.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 The draft guidance is intended to better align the choice of statistical methods with questions of regulatory importance and to improve the reliability of decisions about and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.

Federal Register, Volume 82 Issue 209 (Tuesday, October 31, 2017)

[Federal Register Volume 82, Number 209 (Tuesday, October 31, 2017)]
[Notices]
[Pages 50433-50434]
From the Federal Register Online [www.thefederalregister.org]
[FR Doc No: 2017-23613]

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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Council for Harmonisation; Draft Guidance for Industry; Availability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.

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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the availability of a draft guidance entitled ``E9(R1) Statistical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 The draft guidance was prepared under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.thefederalregister.org/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

Document Created: 2018-10-25 10:19:01
Document Modified: 2018-10-25 10:19:01

Category		Regulatory Information
Collection		Federal Register
sudoc Class		AE 2.7: GS 4.107: AE 2.106:
Publisher		Office of the Federal Register, National Archives and Records Administration
Section		Notices
Action		Notice of availability.
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.
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.
FR Citation		82 FR 50433

82 FR 50433 - E9(R1) Statistical Principles for Clinical Trials: Addendum: Estimands and Sensitivity Analysis in Clinical Trials; International Council for Harmonisation; Draft Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration

Federal Register Volume 82, Issue 209 (October 31, 2017)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration