[Federal Register Volume 83, Number 105 (Thursday, May 31, 2018)]
[Notices]
[Pages 25015-25018]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-11647]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2011-N-0908]


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 or Agency) is announcing 
an opportunity for public comment on the proposed collection of certain 
information by the Agency. Under the Paperwork Reduction Act of 1995 
(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

[[Page 25016]]

solicits comments on the collection of information concerning the 
establishment and operation of clinical trial data monitoring 
committees.

DATES: Submit either electronic or written comments on the collection 
of information by July 30, 2018.

ADDRESSES: You may submit comments as follows. Please note that late, 
untimely filed comments will not be considered. Electronic comments 
must be submitted on or before July 30, 2018. The https://www.regulations.gov electronic filing system will accept comments until 
midnight Eastern Time at the end of July 30, 2018. Comments received by 
mail/hand delivery/courier (for written/paper submissions) will be 
considered timely if they are postmarked or the delivery service 
acceptance receipt is on or before that date.

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2011-N-0908 for ``Agency Information Collection Activities; 
Proposed Collection; Comment Request; Guidance for Clinical Trial 
Sponsors: Establishment and Operation of Clinical Trial Data Monitoring 
Committees.'' Received comments, those filed in a timely manner (see 
ADDRESSES), will be placed in the docket and, except for those 
submitted as ``Confidential Submissions,'' publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. 
and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Ila S. Mizrachi, Office of Operations, 
Food and Drug Administration, Three White Flint North, 10A-12M, 11601 
Landsdown St., North Bethesda, MD 20852, 301-796-7726, 
[email protected].

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

[[Page 25017]]

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 referenced in this 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 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;
     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 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. 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

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and 812.150 have been approved under OMB control number 0910-0078.
    FDA estimates the burden of this collection of information 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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\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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                                                                    Number of
   Section of guidance/recordkeeping activity       Number of      records per    Total annual       Average burden per recordkeeping       Total hours
                                                  recordkeepers   recordkeeper       records
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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
rrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrr
    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    Total annual        Average burden per disclosure         Total hours
                                                   respondents   per 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 the              370               2             740  1......................................             740
 sponsor.
                                                --------------------------------------------------------------------------------------------------------
    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: May 24, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-11647 Filed 5-30-18; 8:45 am]
 BILLING CODE 4164-01-P


