Notice2021-18235
Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment Request; Establishment and Operation of Clinical Trial Data Monitoring Committees
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Published
August 25, 2021
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA, Agency, or we) 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.
Full Text
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<title>Federal Register, Volume 86 Issue 162 (Wednesday, August 25, 2021)</title>
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[Federal Register Volume 86, Number 162 (Wednesday, August 25, 2021)]
[Notices]
[Pages 47505-47507]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2021-18235]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2021-N-0356]
Agency Information Collection Activities; Submission for Office
of Management and Budget Review; Comment Request; 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, Agency, or we) 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: Submit written comments (including recommendations) on the
collection of information by September 24, 2021.
ADDRESSES: To ensure that comments on the information collection are
received, OMB recommends that written comments be submitted to <a href="https://www.reginfo.gov/public/do/PRAMain">https://www.reginfo.gov/public/do/PRAMain</a>. Find this particular information
collection by selecting ``Currently under Review--Open for Public
Comments'' or by using the search function. The OMB control number for
this information collection is 0910-0581. Also include the FDA docket
number found in brackets in the heading of this document.
FOR FURTHER INFORMATION CONTACT: Domini Bean, Office of Operations,
Food and Drug Administration, Three White Flint North, 10A-12M, 11601
Landsdown St., North Bethesda, MD 20852, 301-796-5733,
<a href="/cdn-cgi/l/email-protection#055557445671646363456361642b6d6d762b626a73"><span class="__cf_email__" data-cfemail="99c9cbd8caedf8ffffd9fffdf8b7f1f1eab7fef6ef">[email protected]</span></a>.
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.
Establishment and Operation of Clinical Trial Data Monitoring
Committees
OMB Control Number 0910-0581--Extension
This collection of information supports Agency regulations and
associated Agency guidance. 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 one or more ongoing clinical trials. The DMC advises the sponsor
regarding the continuing safety of current trial subjects and those yet
to be recruited to the trial, as well as the continuing validity and
scientific merit of the trial.
The guidance document entitled ``Guidance for Clinical Trial
Sponsors: Establishment and Operation of Clinical Trial Data Monitoring
Committees'' (March 2006) 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 and is available from our website
at: <a href="https://www.fda.gov/media/75398/download">https://www.fda.gov/media/75398/download</a>. The guidance addresses
the roles, responsibilities, and operating procedures of DMCs and
describes certain reporting and recordkeeping responsibilities,
including the following: (1) Sponsor reporting to FDA on DMC
recommendations related to safety; (2) standard operating procedures
(SOPs) for DMCs; (3) DMC meeting records; (4) sponsor notification to
the DMC regarding waivers; and (5) DMC reports based on meeting minutes
to the sponsor.
1. 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)) (21 CFR 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.''
2. SOPs for DMCs
In the guidance, FDA recommends that sponsors establish procedures
to do the following things:
<bullet> Assess potential conflicts of interest of proposed DMC
members;
<bullet> ensure that those with serious conflicts of interest are
not included in the DMC;
[[Page 47506]]
<bullet> 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;
<bullet> identify and disclose any concurrent service of any DMC
member on other DMCs of the same, related, or competing products;
<bullet> ensure separation, and designate a different statistician
to advise on the management of the trial, if the primary trial
statistician takes on the responsibility for interim analysis and
reporting to the DMC; and
<bullet> minimize the risks of bias that are associated with an
arrangement under which the primary trial 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.
3. 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 (21 CFR 314.50(d)(5)(ii)).
4. Sponsor Notification to the DMC Regarding Waivers
The sponsor must report to FDA certain serious and unexpected
adverse events in drugs and biologics trials (Sec. 312.32) and
unanticipated adverse device effects in the case of device trials (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.
5. DMC Reports of Meeting Minutes to the Sponsor
The Agency recommends in the guidance that DMCs should 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.
Description of the 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. Table 3
of this document provides the burden estimate of the annual third-party
disclosure burden for the information to be submitted in accordance
with the guidance.
Reporting, Recordkeeping, and Third-Party Disclosure Burdens: Based
on information from FDA review divisions, FDA estimates that there are
approximately 740 clinical trials with DMCs regulated by the Center for
Biologics Evaluation and Research, the Center for Drugs 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. 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. 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 of
the meeting records should be maintained per clinical trial.
The ``Average Burden per Response'' and ``Average Burden per
Recordkeeping'' are based on FDA's experience with comparable
recordkeeping and reporting provisions applicable to FDA regulated
industry. The ``Average Burden per Response'' includes the time the
respondent would spend reviewing, gathering, and preparing the
information to be submitted to the DMC, FDA, or the sponsor. The
``Average Burden per Recordkeeping'' includes the time to record,
gather, and maintain the information.
The information collection provisions in the guidance for 21 CFR
312.30, 312.32, 312.38, 312.55, and 312.56 have been approved under OMB
control number 0910-0014; 21 CFR 314.50 has been approved under OMB
control number 0910-0001; and 21 CFR 812.35 and 812.150 have been
approved under OMB control number 0910-0078.
In the Federal Register of April 29, 2021 (86 FR 22690), we
published a 60-day notice requesting public comment on the proposed
collection of information. No comments were received.
We estimate the burden of the information collection as follows:
Table 1--Estimated Annual Reporting Burden \1\
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Number of
Section of guidance/reporting activity Number of responses per Total annual Average burden per response Total hours
respondents respondent responses
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5.--Sponsor reporting to FDA on DMC 37 1 37 0.50 (30 minutes)........................ 18.5
recommendations related to safety.
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Total.................................... .............. .............. .............. ......................................... 18.5
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
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Table 2--Estimated Annual Recordkeeping Burden \1\
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Number of Average burden
Section of guidance/ Number of records per Total annual per Total hours
recordkeeping activity recordkeepers recordkeeper records recordkeeping
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4.1. and 6.4--SOPs for DMCs..... 37 1 37 8 296
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.
Table 3--Estimated Annual Third-Party Disclosure Burden \1\
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Number of
Section of guidance/disclosure activity Number of disclosures per Total annual Average burden per disclosure Total hours
respondents respondent disclosures
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4.4.1.2.--Sponsor notification to the DMC 1 1 1 0.25 (15 minutes)....................... 0.25
regarding waivers.
4.4.3.2.--DMC reports of meeting minutes to 370 2 740 1....................................... 740
the sponsor.
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Total.................................... .............. ............... .............. ........................................ 740.25
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
Based on a review of the information collection since our last
request for OMB approval, we have made no adjustments to our burden
estimate.
Dated: August 5, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2021-18235 Filed 8-24-21; 8:45 am]
BILLING CODE 4164-01-P
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