[Federal Register Volume 66, Number 93 (Monday, May 14, 2001)]
[Notices]
[Pages 24390-24391]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-12026]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 99D-3082]


International Conference on Harmonisation; Choice of Control 
Group and Related Issues in Clinical Trials; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a guidance entitled ``E10 Choice of Control Group and 
Related Issues in Clinical Trials.'' The guidance was prepared under 
the auspices of the International Conference on Harmonisation of 
Technical Requirements for Registration of Pharmaceuticals for Human 
Use (ICH). The guidance sets forth general principles that are relevant 
to all controlled trials and are especially pertinent to the major 
clinical trials intended to demonstrate drug (including biological 
drug) efficacy. The guidance describes the principal types of control 
groups and discusses their appropriateness in particular situations. 
The guidance is intended to assist sponsors and investigators in the 
choice of control groups for clinical trials.

DATES: This guidance is effective May 14, 2001. Submit written comments 
on agency guidances at any time.

ADDRESSES: Submit written requests for single copies of the guidance to 
the Drug Information Branch (HFD-210), Center for Drug Evaluation and 
Research, Food and Drug Administration, 5600 Fishers Lane, Rockville, 
MD 20857, or the Office of Communication, Training and Manufacturers 
Assistance (HFM-40), Center for Biologics Evaluation and Research 
(CBER), 1401 Rockville Pike, Rockville, MD 20852-1448, 301-827-3844, 
FAX: 888-CBERFAX. Send two self-addressed adhesive labels to assist the 
office in processing your requests. Submit written comments on the 
guidance to the Dockets Management Branch (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. See 
the SUPPLEMENTARY INFORMATION section for electronic access to the 
guidance. Requests and comments should be identified with the docket 
number found in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT:
    Regarding the guidance: Robert Temple, Center for Drug Evaluation 
and Research (HFD-4), Food and Drug Administration, 5600 Fishers Lane, 
Rockville, MD 20857, 301-594-6758.
    Regarding the ICH: Janet J. Showalter, Office of International 
Affairs (HFG-1), Food and Drug Administration, 5600 Fishers Lane, 
Rockville, MD 20857, 301-827-0864.

SUPPLEMENTARY INFORMATION:

I. Background

    In recent years, many important initiatives have been undertaken by 
regulatory authorities and industry associations to promote 
international harmonization of regulatory requirements. FDA has 
participated in many meetings designed to enhance harmonization and is 
committed to seeking scientifically based harmonized technical 
procedures for pharmaceutical development. One of the goals of 
harmonization is to identify and then reduce differences in technical 
requirements for drug development among regulatory agencies.
    ICH was organized to provide an opportunity for tripartite 
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 among three regions: The European Union, Japan, 
and the United States. The six ICH sponsors are the European 
Commission, the European Federation of Pharmaceutical Industries 
Associations, the Japanese Ministry of Health and Welfare, the Japanese 
Pharmaceutical Manufacturers Association, the Centers for Drug 
Evaluation and Research and Biologics Evaluation and Research, FDA, and 
the Pharmaceutical Research and Manufacturers of America. The ICH 
Secretariat, which coordinates the preparation of documentation, is 
provided by the International Federation of Pharmaceutical 
Manufacturers Associations (IFPMA).
    The ICH Steering Committee includes representatives from each of 
the ICH sponsors and the IFPMA, as well as observers from the World 
Health Organization, the Canadian Health Protection Branch, and the 
European Free Trade Area.
    In accordance with the agency's regulation on good guidance 
practices (GGP) (21 CFR 10.115; 65 FR 56468, September 19, 2000), this 
document is being called a guidance, rather than a guideline.
    To facilitate the process of making ICH guidances available to the 
public, the agency has changed its procedures for publishing ICH 
guidances. Beginning April 2000, we no longer include the text of ICH 
guidances in the Federal Register. Instead, we will publish a notice in 
the Federal Register announcing the availability of an ICH guidance. 
The ICH guidance is placed in the docket and can be obtained through 
regular agency sources (see the ADDRESSES section). Draft ICH guidances 
are left in the original ICH format. Final guidances are reformatted to 
conform to the GGP style before publication.
    In the Federal Register of September 24, 1999 (64 FR 51767), FDA 
published a draft tripartite guidance entitled ``E10 Choice of Control 
Group in Clinical Trials.'' The notice gave interested persons an 
opportunity to submit comments by December 23, 1999.

[[Page 24391]]

    After consideration of the comments received and revisions to the 
guidance, a final draft of the guidance was submitted to the ICH 
Steering Committee and endorsed by the three participating regulatory 
agencies in July 2000.
    This guidance sets forth general principles that are relevant to 
all controlled trials and are especially pertinent to the major 
clinical trials intended to demonstrate drug (including biological 
drug) efficacy. The guidance includes a description of the five 
principal types of controls, a discussion of two important purposes of 
clinical trials, and an exploration of the critical issue of assay 
sensitivity, i.e., whether a trial could have detected a difference 
between treatments when there was a difference, a particularly 
important issue in noninferiority/equivalence trials. In addition, the 
guidance presents a detailed description of each type of control and 
considers, for each: (1) Its ability to minimize bias; (2) ethical and 
practical issues associated with its use; (3) its usefulness and the 
quality of inference in particular situations; (4) modifications of 
study design or combinations with other controls that can resolve 
ethical, practical, or inferential concerns; and (5) its overall 
advantages and disadvantages.
    This guidance represents the agency's current thinking on the 
choice of control group in clinical trials. It does not create or 
confer any rights for or on any person and does not operate to bind FDA 
or the public. An alternative approach may be used if such approach 
satisfies the requirements of the applicable statutes and regulations.

II. Comments

    Interested persons may submit to the Dockets Management Branch 
(address above) written comments on the guidance at any time. Two 
copies of any comments are to be submitted, except that individuals may 
submit one copy. Comments are to be identified with the docket number 
found in brackets in the heading of this document. The guidance and 
received comments may be seen in the Dockets Management Branch between 
9 a.m. and 4 p.m., Monday through Friday.

III. Electronic Access

    Persons with access to the Internet may obtain the document at 
http://www.fda.gov/cder/guidance/index.htm or http://www.fda.gov/cber/publications.htm.

    Dated: May 4, 2001.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 01-12026 Filed 5-11-01; 8:45 am]
BILLING CODE 4160-01-S