
[Federal Register Volume 80, Number 174 (Wednesday, September 9, 2015)]
[Notices]
[Pages 54297-54299]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-22680]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

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


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; 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) is announcing that a 
proposed collection of information has been submitted to the Office of 
Management and Budget (OMB) for review and clearance under the 
Paperwork Reduction Act of 1995.

DATES: Fax written comments on the collection of information by October 
9, 2015.

ADDRESSES: To ensure that comments on the information collection are 
received, OMB recommends that written comments be faxed to the Office 
of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer, 
FAX: 202-395-7285, or emailed to oira_submission@omb.eop.gov. All 
comments should be identified with the OMB control number 0910-0581. 
Also include the FDA 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: In compliance with 44 U.S.C. 3507, FDA has 
submitted the following proposed collection of information to OMB for 
review and clearance.

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 (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;

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     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 Respondents: The submission and data collection 
recommendations described in this document affect sponsors of clinical 
trials and DMCs.
    Burden Estimate: Table 1 provides the burden estimate of the annual 
reporting burden for the information to be submitted in accordance with 
the guidance. Table 2 provides the burden estimate of the annual 
recordkeeping burden for the information to be maintained in accordance 
with the guidance. Table 3 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; Sec.  314.50 has been approved under OMB 
control number 0910-0001; and 21 CFR 812.35 and 812.150 have been 
approved under OMB control number 0910-0078.
    In the Federal Register of March 27, 2015 (80 FR 16402), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. No comments were received.
    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   0.5 (30 min.).........................            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.


[[Page 54299]]


                                                   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
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    Total.....................................  ..............  ..............  ..............  ........................................           1,036
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.


                                               Table 3--Estimated Annual Third-Party Disclosure Burden \1\
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                                                                   Number of
                                                   Number of      disclosures    Total annual
    Section of guidance/disclosure activity       respondents         per         disclosures         Average burden per disclosure         Total hours
                                                                  respondent
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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.
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    Total.....................................  ..............  ..............  ..............  ........................................          740.25
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.


    Dated: September 3, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-22680 Filed 9-8-15; 8:45 am]
 BILLING CODE 4164-01-P


