Agency Information Collection Activities; Proposed Collection; Comment Request; Guidance for Clinical Trial Sponsors: Establishment and Operation of Clinical Trial Data Monitoring Committees, 16402-16405 [2015-07009]
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Federal Register / Vol. 80, No. 59 / Friday, March 27, 2015 / Notices
(Ebola). Ebola is a type of viral
hemorrhagic fever that is often fatal in
humans and nonhuman primates. Ebola
can spread through human-to-human
transmission, with infection resulting
from direct contact (through broken skin
or mucous membranes) with the blood,
secretions, droplets, or other body fluids
of infected people, and indirectly from
contact with surfaces or items (such as
needles) contaminated with such fluids.
With respect to viral hemorrhagic
fevers, placement on the DNB list and
associated Lookout record is requested
for people known or suspected to have
a viral hemorrhagic fever. Placement
may also be requested for people
without symptoms who have been
exposed to a viral hemorrhagic fever,
particularly if these individuals intend
to travel against public health
recommendations. Even though people
without symptoms are not infectious,
these restrictions are requested because
of the possibility that symptoms could
develop during travel, particularly long
international flights. Exposure is
determined through a CDC risk factor
assessment using information available
from a variety of public health, medical
and other official sources. Examples of
types of potential exposure to viral
hemorrhagic fevers contained within the
CDC risk factor assessment include the
following. It should be noted that not all
of these exposures may result in travel
restrictions.
• Having been in a country with
widespread Ebola virus transmission
within the past 21 days and, although
having had no known exposures, is
showing symptoms
• Percutaneous (e.g., needle stick) or
mucous membrane exposure to blood
or body fluids of a person with Ebola
while the person was showing
symptoms
• Exposure to the blood or body fluids
(including but not limited to feces,
saliva, sweat, urine, vomit, and
semen) of a person with Ebola while
the person was showing symptoms
without appropriate personal
protective equipment (PPE) (see
https://www.cdc.gov/vhf/ebola/hcp/
procedures-for-ppe.html)
• Laboratory processing of blood or
body fluids of a person with Ebola
while the person was showing
symptoms without appropriate PPE or
standard biosafety protections
• Direct contact with a dead body
without appropriate PPE in a country
with widespread Ebola virus
transmission (see https://www.cdc.gov/
vhf/ebola/outbreaks/2014-west-africa/
distribution-map.html)
• Having lived in the immediate
household and provided direct care to
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a person with Ebola while the person
was showing symptoms
• In countries with widespread Ebola
virus transmission: Direct contact
while using appropriate PPE with a
person with Ebola while the person
was showing symptoms, or with the
person’s body fluids, or any direct
patient care in other healthcare
settings
• Close contact in households,
healthcare facilities, or community
settings with a person with Ebola
while the person was showing
symptoms
Æ Close contact is defined as not
wearing appropriate PPE within
approximately 3 feet (1 meter) of a
person with Ebola while the person
was showing symptoms
• Having brief direct contact (e.g.,
shaking hands), while not wearing
appropriate PPE, with a person with
Ebola while the person was in the
early stage of disease
• In countries without widespread
Ebola virus transmission: Direct
contact while using appropriate PPE
with a person with Ebola while the
person was showing symptoms
• Traveled on an aircraft with a person
with Ebola while the person was
showing symptoms
Exposure risk factors, such as those just
described, will be considered by HHS/
CDC in their totality when determining
whether an individual meets the first
criteria for placement on the DNB List,
as described in Section I of this notice.
HHS/CDC would also consider other
facts and information it may have to
make a decision with respect to the
other criteria, as described in Section I
of this notice. It should be noted that all
facts are considered when applying the
criteria. Again, with the exception of the
first criteria, not all of the other criteria
need to be present for HHS/CDC to
make a request to DHS to have an
individual placed on DNB and Lookout.
HHS/CDC would also consider these
risk factors when assessing an
individual who has been in a country
where outbreaks of viral hemorrhagic
fevers were occurring and refuses to
comply with a public health assessment,
and otherwise meets the travel
restriction criteria. Refusing to comply
with a public health risk assessment in
this situation could include refusing to
provide relevant information that would
allow public health officials to assess
the exposure risk.
V. Provisions of This Notice
HHS/CDC will make requests of DHS
based on the criteria in this notice
effective immediately. Individuals who
have had their travel temporarily
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restricted as a result of placement on the
DNB list and associated Lookout records
may submit a written response to the
Director, Division of Global Migration
and Quarantine, if they believe that
HHS/CDC has erred in its public health
request to DHS. The response should be
addressed to: Director, Division of
Global Migration and Quarantine,
ATTN: Travel Restriction and
Intervention Activity, Centers for
Disease Control and Prevention, 1600
Clifton Road, MS E–03, Atlanta, GA
30329. Responses may also be faxed to
CDC at (404) 718–2158 or emailed to
travelrestrictions@cdc.gov.
As part of the response, individuals
should include the reference number
listed in the notification letter they
received and any facts or other evidence
indicating why they believe that HHS/
CDC’s public health request was made
in error.
The policy and program operations
described above will become effective
on March 27, 2015.
Dated: March 24, 2015.
Sylvia M. Burwell,
Secretary.
[FR Doc. 2015–07118 Filed 3–26–15; 8:45 am]
BILLING CODE 4163–18–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.
ACTION:
Notice.
The Food and Drug
Administration (FDA) is announcing an
opportunity for public comment on the
proposed collection of certain
information by the Agency. Under the
Paperwork Reduction Act of 1995 (the
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 solicits comments on
the collection of information concerning
the establishment and operation of
clinical trial data monitoring
committees.
SUMMARY:
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Federal Register / Vol. 80, No. 59 / Friday, March 27, 2015 / Notices
Submit either electronic or
written comments on the collection of
information by May 26, 2015.
DATES:
Submit electronic
comments on the collection of
information to https://
www.regulations.gov. Submit written
comments on the collection of
information to the Division of Dockets
Management (HFA–305), Food and Drug
Administration, 5630 Fishers Lane, Rm.
1061, Rockville, MD 20852. All
comments should be identified with the
docket number found in brackets in the
heading of this document.
ADDRESSES:
FDA
PRA Staff, Office of Operations, Food
and Drug Administration, 8455
Colesville Rd., COLE–14526, Silver
Spring, MD 20993–0002, PRAStaff@
fda.hhs.gov.
FOR FURTHER INFORMATION CONTACT:
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.
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SUPPLEMENTARY INFORMATION:
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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
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, 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
(section 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;
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• 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 (section
314.50(d)(5)(ii) (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
(section 312.32) and unanticipated
adverse device effects in the case of
device trials (section 812.150(b)(1) (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 Respondents: The
submission and data collection
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Federal Register / Vol. 80, No. 59 / Friday, March 27, 2015 / Notices
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,
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 No.
0910–0014; 21 CFR 314.50 has been
approved under OMB Control No. 0910–
0001; and 21 CFR 812.35 and 812.150
have been approved under OMB Control
No. 0910–0078.
FDA estimates the burden of this
collection of information as follows:
TABLE 1—ESTIMATED ANNUAL REPORTING BURDEN 1
Section of guidance/reporting activity
Number of
respondents
Number of
responses per
respondent
Total annual
responses
Average burden
per response
Total hours
5. Sponsor reporting to FDA on DMC recommendations related to safety .........................
37
1
37
0.50 (30 min.)
18.5
Average burden
per
recordkeeping
Total hours
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
records per
recordkeeper
Number of
recordkeepers
Section of guidance/recordkeeping activity
Total annual
records
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
4.4.1.2. Sponsor notification to the DMC regarding waivers .......................................................
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Number of
disclosures per
respondent
Number of
respondents
Section of guidance/disclosure activity
1
Total annual
disclosures
1
Average burden
per disclosure
1
0.25
(15 minutes)
4.4.3.2. DMC reports of meeting minutes to the
sponsor .............................................................
370
2
740
1
Total ..............................................................
............................
............................
..........................
..........................
1 There
are no capital costs or operating and maintenance costs associated with this collection of information.
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Total hours
0.25
740
740.25
Federal Register / Vol. 80, No. 59 / Friday, March 27, 2015 / Notices
Dated: March 23, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015–07009 Filed 3–26–15; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Centers for Disease Control and
Prevention
[60Day–15–15UX: Docket No. CDC–2015–
0011]
Proposed Data Collection Submitted
for Public Comment and
Recommendations
Centers for Disease Control and
Prevention (CDC), Department of Health
and Human Services (HHS).
ACTION: Notice with comment period.
AGENCY:
The Centers for Disease
Control and Prevention (CDC), as part of
its continuing efforts to reduce public
burden and maximize the utility of
government information, invites the
general public and other Federal
agencies to take this opportunity to
comment on proposed and/or
continuing information collections, as
required by the Paperwork Reduction
Act of 1995. This notice invites
comment on ‘‘Continuing and New
International and U.S. Data Collections
from the 2014 CDC Ebola Virus Disease
Emergency Response’’. Under the
current 60-day Federal Register Notice,
the CDC is announcing its intention to
seek three-year OMB approval to
continue several Ebola-related
information collections beyond their
current emergency expiration dates and
to conduct newly proposed information
collections within international borders
of Ebola-affected West African countries
and within the domestic borders of
State, Territorial and Local (STL) public
health authorities in the U.S. These
existing ‘‘source’’ information
collections and new information
collection requests (ICRs) will be
submitted under four ‘‘destination’’
ICRs for Office of Management and
Budget (OMB) approval.
DATES: Written comments must be
received on or before May 26, 2015.
ADDRESSES: You may submit comments,
identified by Docket No. CDC–2015–
0011, by any of the following methods:
• Federal eRulemaking Portal:
Regulation.gov. Follow the instructions
for submitting comments.
• Mail: Leroy A. Richardson,
Information Collection Review Office,
Centers for Disease Control and
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SUMMARY:
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Prevention, 1600 Clifton Road NE., MS–
D74, Atlanta, Georgia 30329.
Instructions: All submissions received
must include the agency name and
Docket Number. All relevant comments
received will be posted without change
to Regulations.gov, including any
personal information provided. For
access to the docket to read background
documents or comments received, go to
Regulations.gov.
Please note: All public comment
should be submitted through the
Federal eRulemaking portal
(Regulations.gov) or by U.S. mail to the
address listed above.
FOR FURTHER INFORMATION CONTACT: To
request more information on the
proposed project or to obtain a copy of
the information collection plan and
instruments, contact the Information
Collection Review Office, Centers for
Disease Control and Prevention, 1600
Clifton Road NE., MS–D74, Atlanta,
Georgia 30329; phone: 404–639–7570;
Email: omb@cdc.gov.
SUPPLEMENTARY INFORMATION: Under the
Paperwork Reduction Act of 1995 (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. In addition, the PRA also
requires Federal agencies to provide a
60-day notice in the Federal Register
concerning each proposed collection of
information, including each new
proposed collection, each proposed
extension of existing collection of
information, and each reinstatement of
previously approved information
collection before submitting the
collection to OMB for approval. To
comply with this requirement, we are
publishing this notice of a proposed
data collection as described below.
Comments are invited on: (a) Whether
the proposed collection of information
is necessary for the proper performance
of the functions of the agency, including
whether the information shall have
practical utility; (b) the accuracy of the
agency’s estimate of the burden of the
proposed collection of information; (c)
ways to enhance the quality, utility, and
clarity of the information to be
collected; (d) ways to minimize the
burden of the collection of information
on respondents, including through the
use of automated collection techniques
or other forms of information
technology; and (e) estimates of capital
or start-up costs and costs of operation,
maintenance, and purchase of services
to provide information. Burden means
the total time, effort, or financial
resources expended by persons to
generate, maintain, retain, disclose or
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16405
provide information to or for a Federal
agency. This includes the time needed
to review instructions; to develop,
acquire, install and utilize technology
and systems for the purpose of
collecting, validating and verifying
information, processing and
maintaining information, and disclosing
and providing information; to train
personnel and to be able to respond to
a collection of information, to search
data sources, to complete and review
the collection of information; and to
transmit or otherwise disclose the
information.
Proposed Project
Continuing and New International
and U.S. Data Collections from the 2014
CDC Ebola Virus Disease Emergency
Response—New—National Center for
Emerging and Zoonotic Infectious
Diseases (NCEZID), Centers for Disease
Control and Prevention (CDC).
Background and Brief Description
The international outbreak of Ebola
virus disease (EVD) in West Africa
began March 10, 2014. The initial cases
were from southern Guinea, near its
rural border with Liberia and Sierra
Leone. Highly mobile populations
contributed to increasing waves of
person-to-person transmission of EVD
that occurred in multiple countries in
West Africa. The Centers for Disease
Control and Prevention (CDC)
Emergency Operations Center (EOC)
was activated on July 9, 2014, to help
coordinate technical assistance and
control activities with international
partners and to deploy teams of public
health experts to the affected countries.
The operations turned to the United
States (U.S.) when the first imported
case of EVD was diagnosed in Texas on
September 30, 2014. In response, on
October 11, 2014, the CDC Quarantine
Stations and the Department of
Homeland Security (DHS) Customs and
Border Patrol (CBP) mobilized to screen,
detect, and refer arriving travelers who
were potential persons at risk for EVD
to appropriate state, territorial, and local
(STL) authorities. The CDC also
increased its commitment to support
STL public health authorities to combat
and control the spread of EVD within
their jurisdictions.
Thus in 2014, the CDC used OMB
emergency clearance procedures to
initiate and expedite multiple urgently
needed information collections in West
Africa, at U.S. ports of entry, and within
STL jurisdictions. These procedures
allowed the agency to accomplish its
primary mission on many fronts to
quickly prevent public harm, illness,
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]]>Agencies
[Federal Register Volume 80, Number 59 (Friday, March 27, 2015)]
[Notices]
[Pages 16402-16405]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2015-07009]
-----------------------------------------------------------------------
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) is announcing an
opportunity for public comment on the proposed collection of certain
information by the Agency. Under the Paperwork Reduction Act of 1995
(the 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 solicits comments on the collection of information
concerning the establishment and operation of clinical trial data
monitoring committees.
[[Page 16403]]
DATES: Submit either electronic or written comments on the collection
of information by May 26, 2015.
ADDRESSES: Submit electronic comments on the collection of information
to https://www.regulations.gov. Submit written comments on the
collection of information to the Division of Dockets Management (HFA-
305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061,
Rockville, MD 20852. All comments should be identified with the docket
number found in brackets in the heading of this document.
FOR FURTHER INFORMATION CONTACT: FDA PRA Staff, Office of Operations,
Food and Drug Administration, 8455 Colesville Rd., COLE-14526, Silver
Spring, MD 20993-0002, 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
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, 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 (section 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 (section 314.50(d)(5)(ii) (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 (section 312.32) and
unanticipated adverse device effects in the case of device trials
(section 812.150(b)(1) (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 Respondents: The submission and data collection
[[Page 16404]]
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 No. 0910-0014; 21 CFR 314.50 has been approved under OMB
Control No. 0910-0001; and 21 CFR 812.35 and 812.150 have been approved
under OMB Control No. 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 Total hours
respondents respondent responses per response
--------------------------------------------------------------------------------------------------------------------------------------------------------
5. Sponsor reporting to FDA on DMC recommendations related 37 1 37 0.50 (30 min.) 18.5
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 Average burden
Section of guidance/recordkeeping activity Number of records per Total annual per Total hours
recordkeepers recordkeeper records recordkeeping
--------------------------------------------------------------------------------------------------------------------------------------------------------
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
--------------------------------------------------------------------------------------
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 per Total annual Average burden Total hours
respondents respondent disclosures per disclosure
--------------------------------------------------------------------------------------------------------------------------------------------------------
4.4.1.2. Sponsor notification to the DMC regarding waivers...... 1 1 1 0.25 0.25
(15 minutes)
4.4.3.2. DMC reports of meeting minutes to the sponsor.......... 370 2 740 1 740
---------------------------------------------------------------------------------------
Total....................................................... ................ ................ ............... ............... 740.25
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
[[Page 16405]]
Dated: March 23, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-07009 Filed 3-26-15; 8:45 am]
BILLING CODE 4164-01-P
