Agency Information Collection Activities; Proposed Collection; Comment Request; Guidance for Clinical Trial Sponsors: Establishment and Operation of Clinical Trial Data Monitoring Committees, 25015-25018 [2018-11647]
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Federal Register / Vol. 83, No. 105 / Thursday, May 31, 2018 / Notices
25015
You can use an alternative approach if
it satisfies the requirements of the
applicable statutes and regulations. This
guidance is not subject to Executive
Order 12866.
I. Background
applications, HDE applications, 510(k)
submissions, IDE applications, and De
Novo classification requests).
Non-clinical bench performance
testing is defined as performance testing
that encompasses all bench testing and
will be dependent upon the specifics of
the actual device or device type. Nonclinical bench performance testing
includes, but is not limited to,
mechanical and biological engineering
performance such as fatigue, wear,
tensile strength, compression, and burst
pressure; bench tests using animal or
human tissue; and animal carcass or
human cadaveric testing. Non-clinical
bench performance testing excludes
biocompatibility evaluation,
sterilization, and animal in vivo
evaluation.
This draft guidance is intended to
help ensure that clear and consistent
information is provided in premarket
submissions containing non-clinical
bench performance testing. The
information in this draft guidance is
intended to be used in conjunction with
other FDA guidance documents,
including device-specific guidances.
FDA is announcing the availability of
a draft guidance for industry and FDA
staff entitled ‘‘Recommended Content
and Format of Complete Test Reports for
Non-Clinical Bench Performance
Testing in Premarket Submissions.’’
FDA has developed this document to
describe relevant information that
should be included in complete test
reports for non-clinical bench
performance testing provided in a
premarket submission (i.e., PMA
II. Significance of Guidance
This draft guidance is being issued
consistent with FDA’s good guidance
practices regulation (21 CFR 10.115).
The draft guidance, when finalized, will
represent the current thinking of FDA
on ‘‘Recommended Content and Format
of Complete Test Reports for NonClinical Bench Performance Testing in
Premarket Submissions.’’ It does not
establish any rights for any person and
is not binding on FDA or the public.
IV. Paperwork Reduction Act of 1995
An electronic copy of the guidance
document is available for download
from the internet. See the
SUPPLEMENTARY INFORMATION section for
information on electronic access to the
guidance. Submit written requests for a
single hard copy of the draft guidance
document entitled ‘‘Recommended
Content and Format of Complete Test
Reports for Non-Clinical Bench
Performance Testing in Premarket
Submissions’’ to the Office of the Center
Director, Guidance and Policy
Development, Center for Devices and
Radiological Health, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 5431, Silver Spring,
MD 20993–0002. Send one selfaddressed adhesive label to assist that
office in processing your request.
FOR FURTHER INFORMATION CONTACT:
Mary Wen, Center for Devices and
Radiological Health, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 1529, Silver Spring,
MD 20993–0002, 240–402–4913.
SUPPLEMENTARY INFORMATION:
III. Electronic Access
Persons interested in obtaining a copy
of the draft guidance may do so by
downloading an electronic copy from
the internet. A search capability for all
Center for Devices and Radiological
Health guidance documents is available
at https://www.fda.gov/MedicalDevices/
DeviceRegulationandGuidance/
GuidanceDocuments/default.htm. This
guidance document is also available at
https://www.regulations.gov. Persons
unable to download an electronic copy
of ‘‘Recommended Content and Format
of Complete Test Reports for NonClinical Bench Performance Testing in
Premarket Submissions’’ may send an
email request to CDRH-Guidance@
fda.hhs.gov to receive an electronic
copy of the document. Please use the
document number 18011 to identify the
guidance you are requesting.
This draft guidance refers to
previously approved collections of
information found in FDA regulations.
These collections of information are
subject to review by the Office of
Management and Budget (OMB) under
the Paperwork Reduction Act of 1995
(44 U.S.C. 3501–3520). The collections
of information in the following FDA
regulations and guidances have been
approved by OMB as listed:
OMB control
No.
21 CFR part or guidance
Topic
807, Subpart E ...........................................................................
814, Subparts A Through E .......................................................
814, Subpart H ...........................................................................
812 ..............................................................................................
De Novo Classification Process (Evaluation of Automatic Class
III Designation).
Premarket Notification ................................................................
Premarket Approval ....................................................................
Humanitarian Device Exemption ................................................
Investigational Device Exemption ..............................................
De Novo Classification process .................................................
Dated: May 24, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018–11603 Filed 5–30–18; 8:45 am]
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BILLING CODE 4164–01–P
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.
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ACTION:
0910–0120
0910–0231
0910–0332
0910–0078
0910–0844
Notice.
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
SUMMARY:
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Federal Register / Vol. 83, No. 105 / Thursday, May 31, 2018 / Notices
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’’).
amozie on DSK3GDR082PROD with NOTICES1
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
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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/201523389.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
PO 00000
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and Drug Administration, Three White
Flint North, 10A–12M, 11601
Landsdown St., North Bethesda, MD
20852, 301–796–7726, PRAStaff@
fda.hhs.gov.
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
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Federal Register / Vol. 83, No. 105 / Thursday, May 31, 2018 / Notices
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.
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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
(§ 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
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• 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
(§ 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 ThirdParty Disclosure Burdens: Based on
information from FDA review divisions,
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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
Number of
respondents
Section of guidance/reporting activity
5. Sponsor reporting to FDA on DMC recommendations related to safety ..
1 There
37
Number of
responses per
respondent
Average
burden per
response
Total annual
responses
1
37
0.50 (30 minutes)
Total hours
18.5
are no capital costs or operating and maintenance costs associated with this collection of information.
TABLE 2—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1
Number of
recordkeepers
Section of guidance/recordkeeping activity
Number of
records per
recordkeeper
Average
burden per
recordkeeping
Total annual
records
Total hours
4.1. and 6.4 SOPs for DMCs .........................................................................
4.4.3.2. DMC meeting records .......................................................................
37
370
1
1
37
370
8 ...........................
2 ...........................
296
740
Total ........................................................................................................
........................
........................
........................
...............................
1,036
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
Number of
respondents
Section of guidance/disclosure activity
Number of
disclosures
per respondent
Average
burden per
disclosure
Total annual
disclosures
Total hours
4.4.1.2. Sponsor notification to the DMC regarding waivers .........................
4.4.3.2. DMC reports of meeting minutes to the sponsor .............................
1
370
1
2
1
740
0.25 (15 minutes)
1 ...........................
0.25
740
Total ........................................................................................................
........................
........................
........................
...............................
740.25
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
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2018–D–1609]
Q12 Technical and Regulatory
Considerations for Pharmaceutical
Product Lifecycle Management;
International Council for
Harmonisation; Draft Guidance for
Industry; Availability
AGENCY:
Electronic Submissions
Food and Drug Administration,
HHS.
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ACTION:
Notice of availability.
The Food and Drug
Administration (FDA or Agency) is
announcing the availability of a
guidance entitled ‘‘Q12 Technical and
Regulatory Considerations for
Pharmaceutical Product Lifecycle
Management; International Council for
Harmonisation.’’ The draft guidance was
SUMMARY:
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prepared under the auspices of the
International Council for Harmonisation
(ICH), formerly the International
Conference on Harmonisation. The draft
guidance, which consists of a Core
Guideline and an Annex, provides a
framework to facilitate the management
of post-approval chemistry,
manufacturing, and controls changes for
new and marketed pharmaceutical drug
substances and drug products, including
marketed chemical and
biotechnological/biological products.
DATES: Submit either electronic or
written comments on the draft guidance
by December 15, 2018, to ensure that the
Agency considers your comment on this
draft guidance before it begins work on
the final version of the guidance.
ADDRESSES: You may submit comments
on any guidance at any time as follows:
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
PO 00000
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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–
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]]>Agencies
[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]
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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
[[Page 25018]]
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\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Number of
Section of guidance/reporting activity Number of responses per Total annual Average burden per response Total hours
respondents respondent responses
--------------------------------------------------------------------------------------------------------------------------------------------------------
5. Sponsor reporting to FDA on DMC 37 1 37 0.50 (30 minutes)...................... 18.5
recommendations related to safety.
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
Table 2--Estimated Annual Recordkeeping Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Number of
Section of guidance/recordkeeping activity Number of records per Total annual Average burden per recordkeeping Total hours
recordkeepers recordkeeper records
--------------------------------------------------------------------------------------------------------------------------------------------------------
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
--------------------------------------------------------------------------------------------------------------------------------------------------------
\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\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Number of
Section of guidance/disclosure activity Number of disclosures Total annual Average burden per disclosure Total hours
respondents per respondent disclosures
--------------------------------------------------------------------------------------------------------------------------------------------------------
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
--------------------------------------------------------------------------------------------------------------------------------------------------------
\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
