[Federal Register: December 30, 2005 (Volume 70, Number 250)]
[Notices]
[Page 77403-77405]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr30de05-66]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 2001D-0489] (formerly Docket No. 01D-0489)
Agency Information Collection Activities; Submission for Office
of Management and Budget Review; Comment Request; Draft Guidance for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 that a
proposed collection of information has been submitted to the Office of
Management and Budget (OMB) for review and clearance under the
Paperwork Reduction Act of 1995.
DATES: Fax written comments on the collection of information by January
30, 2005.
ADDRESSES: OMB is still experiencing significant delays in the regular
mail, including first class and express mail, and messenger deliveries
are not being accepted. To ensure that comments on the information
collection are received, OMB recommends that written comments be faxed
to the Office of Information and Regulatory Affairs, OMB, Attn: Fumie
Yokota, Desk Officer for FDA, FAX: 202-395-6974.
Submit written requests for single copies of the draft guidance
dated December 2005 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. Send one self-addressed adhesive label to
assist the office in processing your requests. The draft guidance may
also be obtained by mail by calling CBER at 1-800-835-4709 or 301-827-
1800. Persons with access to the Internet may obtain the draft guidance
at either http://www.fda.gov/cber/guidelines.htm or http://www.fda.gov/ohrms/dockets/default
.htm.
FOR FURTHER INFORMATION CONTACT: Jonna Capezzuto, Office of Management
Programs (HFA-250), Food and Drug Administration, 5600 Fishers Lane,
Rockville, MD 20857, 301-827-4659.
SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has
submitted the following proposed collection of information to OMB for
review and clearance.
Draft Guidance for Clinical Trial Sponsors: Establishment and Operation
of Clinical Trial Data Monitoring Committees
The draft guidance document, when finalized, is intended to assist
sponsors of clinical trials in determining when a Data Monitoring
Committee (DMC) is needed for study monitoring, and how such committees
should operate. The draft guidance was revised based on public
comments. The draft guidance addresses the roles, responsibilities, and
operating procedures of DMCs, and describes certain reporting and
recordkeeping responsibilities including the following: (1) Sponsor
notification to the DMC regarding waivers of expedited reporting, (2)
DMC reports of meeting minutes to the sponsor, (3) sponsor reporting to
FDA on DMC safety-related recommendations, (4) standard operating
procedures (SOPs) for DMCs, (5) DMC meeting records, and (6) DMC
reports to the sponsor.
A. Sponsor Notification to the DMC Regarding Waivers
The sponsor has the responsibility of reporting to FDA serious,
unexpected adverse events in drugs and biologics trials under part 312
(21 CFR part 312) in Sec. 312.32 and unanticipated adverse events in
the case of device trials under part 812 (21 CFR part 812) in Sec.
812.150(b)(1). We recommend in the draft guidance that sponsors notify
DMCs about any waivers granted by FDA for expedited reporting of
certain serious events.
B. DMC Report of Meeting Minutes to the Sponsor
FDA 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.
C. Sponsor reporting to FDA on DMC Safety-Related Recommendations
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
[[Page 77404]]
serious. Nevertheless, we recommend in the draft 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.''
D. Standard Operating Procedures
In the draft guidance, FDA recommends 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 on 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 are associated with such
arrangements, if the primary study statistician takes on the
responsibility for interim analysis and reporting to the DMC, and it
appears infeasible or highly impractical for any other statistician to
take over responsibilities related to trial management.
E. Meeting Records
FDA 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) (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 revised 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
revised draft guidance.
Based on information from FDA review divisions, FDA estimates there
are currently 740 clinical trials with DMCs regulated by CBER, 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 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 draft
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. 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 the
meeting minutes to the sponsor. One set of both of the 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.
In the Federal Register of November 20, 2001 (FR 66 58151), FDA
published a 60-day notice requesting public comment on the information
collection provisions in the draft guidance. FDA received a number of
comments on the draft guidance, however, only one letter of comment
included comments regarding the information collection provisions.
The comment stated that the ``Hours per Response'' were
underestimated for the SOPs and Data Analysis Plan (statistical
approach) listed in table 1 of the 60-day notice (66 FR 58151 at 58153)
for the ``Estimated Annual Reporting Burden.'' The comment requested an
increase to 12 hours for these burdens from the previous estimate of 4
hours for the SOPs, and 8 hours for the Data Analysis Plan.
In revising the draft guidance, FDA is adding the applicable
regulations throughout the draft guidance including the regulations
associated with these two burden estimates. The burden associated with
the submission of SOPs and the statistical approach in table 1 of the
60-day notice is covered under Sec. Sec. 312.23 and 812.150(b)(10) and
is approved under OMB Control Nos. 0910-0014 and 0910-0078. Therefore,
these categories were removed from table 1 and no change in the burden
estimates is necessary.
Based on revisions to the draft guidance, however, two additional
information collection burdens have been added to table 1 of this
document, and one additional previous information collection burden was
deleted from table 1 of the 60-day notice.
The information collection provisions in the draft guidance for
Sec. Sec. 312.30, 312.32, 312.38, 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 and
812.150 have been approved under OMB Control No. 0190-0078.
The total estimated burden for both the reporting and recordkeeping
burdens under the draft guidance are 1,794.75 hours.
Table 1.--Estimated Annual Reporting Burden\1\
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Section of Draft
Guidance/ No. of Annual Frequency Total Annual Hours per
Reporting Respondents per Response Responses Response Total Hours
Activity
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4.4.1.2 Sponsor 1 1 1 .25 .25
notification to
the DMC
regarding
waivers of
expedited
reporting
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[[Page 77405]]
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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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Reporting No. of Annual Frequency Total Annual
Activity Recordkeepers per Recordkeeping Records Hours per Record Total Hours
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4.1 and 6.4 37 1 37 8 296
SOPs for DMCs
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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.
Dated: December 22, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E5-8115 Filed 12-29-05; 8:45 am]
BILLING CODE 4160-01-S