[Federal Register Volume 66, Number 224 (Tuesday, November 20, 2001)]
[Notices]
[Pages 58151-58153]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-28962]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 01D-0489]
Draft ``Guidance for Clinical Trial Sponsors on the Establishment
and Operation of Clinical Trial Data Monitoring Committees;''
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 draft document entitled ``Guidance for Clinical Trial
Sponsors on the Establishment and Operation of Clinical Trial Data
Monitoring Committees'' dated November 2001. The draft guidance
document, when finalized, will assist sponsors of clinical trials in
determining when a data monitoring committee (DMC) is needed for
optimal study monitoring and how such committees should operate.
DATES: Submit written or electronic comments on the draft guidance to
ensure their adequate consideration in preparation of the final
document by February 19, 2002. General comments on agency guidance
documents are welcome at any time. Submit written or electronic
comments on the collections of information by January 22, 2002.
ADDRESSES: Submit written requests for single copies of the draft
guidance to the Office of Communication, Training, and Manufacturers
Assistance (HFM-40), Center for Biologics Evaluation and Research
(CBER), Food and Drug Administration, 1401 Rockville Pike, Rockville,
MD 20852-1448; the Drug Information Branch (HFD-210), Center for Drug
Evaluation and Research (CDER), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857; or the Division of Small
Manufacturers, International, and Consumer Assistance (HFZ-220), Center
for Devices and Radiological Health (CDRH), Food and Drug
Administration, 1350 Piccard Dr., Rockville, MD 20850. Send one self-
addressed adhesive label to assist the office in processing your
requests. The document may also be obtained by mail by calling the CBER
Voice Information System at 1-800-835-4709 or 301-827-1800, or by fax
by calling the FAX Information System at 1-888-CBER-FAX or 301-827-
3844; or the CDRH Facts-On-Demand system at 1-800-899-0381 or 301-827-
0111. See the SUPPLEMENTARY INFORMATION section for electronic access
to the draft guidance document.
Submit written comments on the document to the Dockets Management
Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm.
1061, Rockville, MD 20852. Submit electronic comments to http://www.fda.gov/dockets/ecomments.
FOR FURTHER INFORMATION CONTACT:
Stephen M. Ripley, Center for Biologics Evaluation and Research
(HFM-17), Food and Drug Administration, 1401 Rockville Pike, Rockville,
MD 20852-1448, 301-827-6210;
Robert Temple, Center for Drug Evaluation and Research (HFD-40),
Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857,
301-594-6758; or
Joanne Less, Center for Devices and Radiological Health (HFZ-403),
Food and Drug Administration, 9200 Corporate Blvd., Rockville, MD
20850, 301-594-1190.
SUPPLEMENTARY INFORMATION:
[[Page 58152]]
I. Background
FDA is announcing the availability of a draft document entitled
``Guidance for Clinical Trial Sponsors on the Establishment and
Operation of Clinical Trial Data Monitoring Committees'' dated November
2001. The draft guidance document, when finalized, will assist sponsors
of clinical trials in determining when a DMC is needed for optimal
study monitoring, and how such committees should operate. The draft
guidance addresses the roles, responsibilities, and operating
procedures of DMCs.
This draft guidance is being issued consistent with FDA's good
guidance practices regulation (21 CFR 10.115). This draft guidance
document represents the agency's current thinking on this topic. 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 requirement of the applicable statutes
and regulations.
II. The Paperwork Reduction Act of 1995
Under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C.
3501-3520), Federal agencies must obtain approval from the Office of
Management and Budget (OMB) for each collection of information they
conduct or sponsor. ``Collection of Information'' is defined in 44
U.S.C. 3502(3) and 5 CFR 1320.3(c) and includes agency requests or
requirements that members of the public submit reports, keep records,
or provide information to a third party. Section 3506(c)(2)(A) of the
PRA (44 U.S.C. 3506(c)(2)(A)) requires Federal agencies to provide a
60-day notice in the Federal Register concerning each proposed
collection of information before submitting the collection to OMB for
approval. To comply with this requirement, FDA is publishing notice of
the proposed collection of information set forth in this document.
With respect to the following collection of information, FDA
invites comments on: (1) Whether the proposed collection of information
is necessary for the proper performance of FDA's functions, including
whether the information will have practical utility; (2) the accuracy
of FDA's estimate of the burden of the proposed collection of
information, including the validity of the methodology and assumptions
used; (3) ways to enhance the quality, utility, and clarity of the
information to be collected; and (4) ways to minimize the burden of the
collection of information on respondents, including through the use of
automated collection techniques, when appropriate, and other forms of
information technology.
Title: Draft Guidance for Clinical Trial Sponsors on the
Establishment and Operation of Clinical Trial Data Monitoring
Committees
Description: FDA is issuing a draft guidance document that will
assist sponsors of clinical trials in determining when a DMC is needed
for optimal study monitoring, and how such committees should operate.
The draft guidance addresses the roles, responsibilities, and operating
procedures of DMCs, and describes certain reporting and recordkeeping
responsibilities including the following: (1) Standard operating
procedures (SOPs); (2) interim reports by a sponsor to a DMC,
statistical approach to FDA, DMC report of meeting minutes to the
sponsor; and (3) meeting records. The information collection provisions
for Sec. 314.50(d)(5)(ii) (21 CFR 314.50(d)(5)(ii)) have been approved
under OMB Control No. 0910-0001.
A. Standard Operating Procedures
Under the draft guidance, the agency recommends that all DMCs have
well-defined SOPs. Subjects to be addressed in SOPs should include, but
may not be limited to, the following:
Schedule and format for meetings,
Format for presentation of data,
Identification of individuals who will have access to
interim data to ensure confidentiality,
Identification of individuals who may attend all or part
of the DMC meetings,
Method and timing of providing DMC members with interim
study reports,
Specification of the statistical approach that will be
used to evaluate treatment effects and approach to considering early
termination of the study for benefit or harm,
Assessment of potential conflicts of interest of proposed
DMC members,
Interaction between FDA and DMC members for certain
products, and
Rapid unblinding of treatment codes to DMC members when
needed.
The agency also recommends that the sponsor submit a description of
the SOPs to FDA.
B. Interim Reports by a Sponsor to a DMC
The agency recommends in the draft guidance that the sponsor or
sponsor's contractor submit an interim report, including information to
be presented by the statistician at the DMC meeting, to the DMC. The
interim report provides the DMC with essential information regarding
the trial upon which they may base their recommendations.
C. Statistical Approach
The agency recommends in the draft guidance that the final
statistical approach be submitted to FDA before initiation of interim
monitoring. FDA reviews this information and may provide comments to
the sponsor.
D. DMC Report of Meeting Minutes to Sponsor
The agency recommends in the draft guidance that the DMC issue a
written report to the sponsor based on the meeting minutes. Reports to
the sponsor should include only those data generally available to the
sponsor. The sponsor may convey the relevant information in this report
to other interested parties such as study investigators. Meeting
minutes or other information that include discussion of confidential
data would not be provided to the sponsor.
E. Meeting Records
The agency recommends in the draft guidance that the DMC or the
group preparing the interim reports to the DMC maintain all meeting
records. This information should be submitted to FDA with the clinical
study report (Sec. 314.50(d)(5)(ii)).
Description of Respondents: The submission and data collection
recommendations described in this document affect sponsors of clinical
trials and DMCs.
Burden Estimate: Table 1 of this document provides the burden
estimate of the annual reporting burden for the information to be
submitted in accordance with the draft guidance. Table 2 of this
document provides the burden estimate of the annual recordkeeping
burden for the information to be maintained in accordance with the
draft guidance.
Reporting and Recordkeeping Burdens
Based on information from FDA review divisions, FDA estimates there
are currently 740 clinical trials with DMCs regulated by CBER, CDER,
and CDRH. FDA estimates that the average length of a clinical trial is
2 years, resulting in an annual estimate of 370 clinical trials.
Because FDA has no information on which to project a change in the use
of DMCs, FDA estimates that the number of clinical trials with DMCs
will not change significantly in the next few years. For purposes of
this information collection, FDA estimates that each sponsor is
responsible for approximately 10 trials,
[[Page 58153]]
resulting in an estimated 37 sponsors affected by the guidance
annually.
Based on information provided to FDA by sponsors that have
typically used DMCs for the kinds of studies for which this guidance
recommends them, FDA estimates that the majority of sponsors have
already prepared SOPs for DMCs, and only a minimum amount of time would
be necessary to revise or update them for use for other clinical
studies. Based on FDA's experience with clinical trials using DMCs, FDA
estimates that the sponsor on average would issue two interim reports
per clinical trial to the DMC. FDA estimates that the DMCs would hold
two meetings per year per clinical trial resulting in the issuance of
two DMC reports of the meeting minutes to the sponsor. One set of both
of the meeting records should be maintained per clinical trial. Based
on FDA's experience with the submission of investigational new drug
applications (INDs), FDA estimates that one statistical approach per
clinical trial would be submitted to FDA.
The hours per response and hours per record are based on FDA's
experience with comparable recordkeeping and reporting provisions
applicable to FDA regulated industry. The hours per response include
the time the respondent would spend reviewing, gathering, and preparing
the information to be submitted to the DMC, FDA, or the sponsor.
Because clinical trials vary greatly in complexity, FDA estimates that
the time needed to prepare and submit an interim report by a sponsor or
sponsor's contractor to the DMC would generally range from 40 to 200
hours with an average of 120 hours for each report. The hours per
record include the time to record, gather, and maintain the
information.
The total estimated burden for both the reporting and recordkeeping
burdens under the draft guidance are 93,684 hours.
FDA invites comments on this analysis of information collection
burdens. FDA estimates the burden of this information collection as
follows:
Table 1.--Estimated Annual Reporting Burden\1\
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Reporting No. of Responses Total Annual
Activity No. of Respondents per Respondent Responses Hours per Response Total Hours
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SOPs 37 1 37 4 148
Interim 370 2 740 120 88,800
reports by
the sponsor
to a DMC
Statistical 370 1 370 8 2,960
approach to
FDA
DMC report 370 2 740 1 740
of meeting
minutes to
the sponsor
Total 92,648
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
Table 2.--Estimated Annual Recordkeeping Burden\1\
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21 CFR No. of Annual Frequency Total Annual Hours per
Section Recordkeepers per Recordkeeping Records Recordkeeper Total Hours
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SOPs 37 1 37 8 296
Meeting 370 1 370 2 740
records
Total 1,036
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
III. Comments
This draft document is being distributed for comment purposes only
and is not intended for implementation at this time. Interested persons
may submit to the Dockets Management Branch (address above) written or
electronic comments regarding this draft guidance document and on the
collection of information. Submit written or electronic comments to
ensure adequate consideration in preparation of the final document by
February 19, 2002. Two copies of any comments are to be submitted,
except that individuals may submit one copy. Comments should be
identified with the docket number found in the brackets in the heading
of this document. A copy of the document and received comments are
available for public examination in the Dockets Management Branch
between 9 a.m. and 4 p.m., Monday through Friday.
IV. Electronic Access
Persons with access to the Internet may obtain the document at
http://www.fda.gov/cber/guidelines.htm, http://www.fda.gov/cder/guidance/index.htm, http://www.fda.gov/cdrh, or http://www.fda.gov/ohrms/dockets/default.htm.
Dated: November 14, 2001.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 01-28962 Filed 11-19-01; 8:45 am]
BILLING CODE 4160-01-S