[Federal Register Volume 73, Number 196 (Wednesday, October 8, 2008)]
[Notices]
[Pages 58970-58972]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-23833]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2008-N-0521]
Agency Information Collection Activities; Proposed Collection;
Comment Request; Guidance for Clinical Trial Sponsors: Establishment
and Operation of Clinical Trial Data Monitoring Committees
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA) is announcing an
opportunity for public comment on the proposed collection of certain
information by the agency. Under the Paperwork Reduction Act of 1995
(the PRA), Federal agencies are required to publish notice in the
Federal Register concerning each proposed collection of information,
including each proposed extension of an existing collection of
information, and to allow 60 days for public comment in response to the
notice. This notice solicits comments on the collection of information
concerning the establishment and operation of clinical trial data
monitoring committees.
DATES: Submit written or electronic comments on the collection of
information by December 8, 2008.
ADDRESSES: Submit electronic comments on the collection of information
to http://www.regulations.gov. Submit written comments on the
collection of information to the Division of Dockets Management (HFA-
305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061,
Rockville, MD 20852. All comments should be identified with the docket
number found in brackets in the heading of this document.
FOR FURTHER INFORMATION CONTACT: Jonna Capezzuto, Office of Information
Management (HFA-710), Food and Drug Administration, 5600 Fishers Lane,
Rockville, MD 20857, 301-796-3794.
SUPPLEMENTARY INFORMATION: Under 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, including
each proposed extension of an existing 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 these topics: (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.
Guidance for Clinical Trial Sponsors: Establishment and Operation of
Clinical Trial Data Monitoring Committees--(OMB Control Number 0910-
0581)--Extension
Sponsors are required to monitor studies evaluating new drugs,
biologics, and devices (21 CFR 312.50 and 312.56 for drugs and
biologics, and 21 CFR 812.40 and 812.46 for devices). Various
individuals and groups play different roles in clinical trial
monitoring. One such group is a Data Monitoring Committee (DMC),
appointed by a sponsor to evaluate the accumulating outcome data in
some trials. A clinical trial DMC is a group of individuals with
pertinent expertise that reviews on a regular basis accumulating data
from an
[[Page 58971]]
ongoing clinical trial. The DMC advises the sponsor regarding the
continuing safety of current participants and those yet to be
recruited, as well as the continuing validity and scientific merit of
the trial.
FDA's guidance document is intended to assist sponsors of clinical
trials in determining when a DMC is needed for monitoring a study, and
how such committees should operate. The guidance addresses the roles,
responsibilities, and operating procedures of DMCs, describes certain
reporting and recordkeeping responsibilities, including the following:
(1) Sponsor notification to the DMC regarding waivers, (2) DMC reports
of meeting minutes to the sponsor, (3) sponsor reports to the FDA on
DMC recommendations related to safety, (4) standard operating
procedures (SOPs) for DMCs, and (5) DMC meeting records.
1. Sponsor Notification to the DMC Regarding Waivers
The sponsor must report to FDA serious unexpected adverse events in
drugs and biologics trials (Sec. 312.32 (21 CFR 312.32)) and
unanticipated adverse events in the case of device trials under (Sec.
812.150(b)(1) (21 CFR 812.150(b)(1))). The agency recommends in the
guidance that sponsors notify DMCs about any waivers granted by FDA for
expedited reporting of certain serious events.
2. DMC Reports of Meeting Minutes to the Sponsor
The agency recommends in the guidance that the DMC issue a written
report to the sponsor based on the DMC 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.
3. Sponsor Reporting to FDA on DMC Recommendations Related to Safety
The requirement of the sponsor to report DMC recommendations
related to serious adverse events in an expedited manner in clinical
trials of new drugs (Sec. 312.32(c)) would not apply when the DMC
recommendation is related to an excess of events not classifiable as
serious. Nevertheless, the agency recommends in the guidance that
sponsors inform FDA about all recommendations related to the safety of
the investigational product whether or not the adverse event in
question meets the definition of ``serious.''
4. Standard Operating Procedures for DMCs
In the guidance, we recommend that sponsors establish procedures to
do the following things:
Assess potential conflicts of interest of proposed DMC
members;
Ensure that those with serious conflicts of interest are
not included in the DMC;
Provide disclosure to all DMC members of any potential
conflicts that are not thought to impede objectivity and, thus, would
not preclude service on the DMC;
Identify and disclose any concurrent service of any DMC
member on other DMCs of the same, related or competing products;
Ensure separation, and designate a different statistician
to advise on the management of the trial, if the primary study
statistician takes on the responsibility for interim analysis and
reporting to the DMC; and
Minimize the risks of bias that arise when the primary
study statistician takes on the responsibility for interim analysis and
reporting to the DMC, if it appears infeasible or highly impractical
for any other statistician to take over responsibilities related to
trial management.
5. DMC Meeting Records
The agency recommends in the 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) (21 CFR 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 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 guidance.
Reporting and Recordkeeping Burdens
Based on information from FDA review divisions, FDA estimates there
are approximately 740 clinical trials with DMCs regulated by the Center
for Biologics Evaluation and Research, the Center for Drug Evaluation
and Research, and the Center for Devices and Radiological Health. 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, resulting in an estimated 37 sponsors that are
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 is
necessary to revise or update them for use for other clinical studies.
FDA receives very few requests for waivers regarding expedited
reporting of certain serious events; therefore, FDA has estimated one
respondent per year to account for the rare instance a request may be
made. FDA estimates that the DMCs would hold two meetings per year per
clinical trial resulting in the issuance of two DMC reports of 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
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 meeting minutes
to the sponsor. One set of both meeting records should be maintained
per clinical trial.
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. The ``Hours per Record'' include the time to record, gather,
and maintain the information.
The information collection provisions in the guidance for
Sec. Sec. 312.30 (21 CFR 312.30), 312.32, 312.38 (21 CFR 312.38),
312.55 (21 CFR 312.55), and 312.56 have been approved under OMB Control
No. 0910-0014; Sec. 314.50 has been approved under OMB Control No.
0910-0001; and Sec. Sec. 812.35 (21 CFR 812.35) and 812.150 have been
approved under OMB Control No. 0910-0078.
FDA estimates the burden of this collection of information as
follows:
[[Page 58972]]
Table 1.--Estimated Annual Reporting Burden\1\
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No. of Annual Frequency per Total Annual Hours Per
Section of Guidance/Reporting Activity Respondents Response Responses Response Total Hours
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4.4.1.2. Sponsor notification to the DMC regarding 1 1 1 .25 .25
waivers
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4.4.3.2. DMC reports of meeting minutes to the sponsor 370 2 740 1 740
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5. Sponsor reporting to FDA on DMC recommendations 37 1 37 .5 18.5
related to safety
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Total 758.75
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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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No. of Annual Frequency Total Annual
Recordkeeping Activity Recordkeepers per Recordkeeping Records Hours Per Record Total Hours
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4.1. and 6.4 SOPs for DMCs 37 1 37 8 296
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4.4.3.2. DMC meeting records 370 1 370 2 740
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Total 1,036
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
Please note that on January 15, 2008, the FDA Division of Dockets
Management Web site transitioned to the Federal Dockets Management
System (FDMS). FDMS is a Government-wide, electronic docket management
system. Electronic comments or submissions will be accepted by FDA only
through FDMS at http://www.regulations.gov.
Dated: September 29, 2008.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E8-23833 Filed 10-7-08; 8:45 am]
BILLING CODE 4160-01-S