[Federal Register Volume 86, Number 162 (Wednesday, August 25, 2021)]
[Notices]
[Pages 47505-47507]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[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 https://www.reginfo.gov/public/do/PRAMain. 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, 
PRAStaff@fda.hhs.gov.

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: https://www.fda.gov/media/75398/download. 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:
     Assess potential conflicts of interest of proposed DMC 
members;
     ensure that those with serious conflicts of interest are 
not included in the DMC;

[[Page 47506]]

     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 trial 
statistician takes on the responsibility for interim analysis and 
reporting to the DMC; and
     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.


[[Page 47507]]


                               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


