[Federal Register Volume 77, Number 77 (Friday, April 20, 2012)]
[Notices]
[Pages 23730-23732]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-9533]



[[Page 23730]]

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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 May 21, 
2012.

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 <a href="/cdn-cgi/l/email-protection#f19e988390ae8284939c988282989e9fb19e9c93df949e81df969e87"><span class="__cf_email__" data-cfemail="cca3a5bead93bfb9aea1a5bfbfa5a3a28ca3a1aee2a9a3bce2aba3ba">[email protected]</span></a>. 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:  Ila S. Mizrachi, Office of 
Information Management, Food and Drug Administration, 1350 Piccard Dr., 
PI50-400B, Rockville, MD 20850, 301-796-7726, <a href="/cdn-cgi/l/email-protection#10597c713e5d796a6271737879507674713e7878633e777f66"><span class="__cf_email__" data-cfemail="20694c410e6d495a5241434849604644410e4848530e474f56">[email protected]</span></a>.

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 (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:
    <bullet> Assess potential conflicts of interest of proposed DMC 
members;
    <bullet> Ensure that those with serious conflicts of interest are 
not included in the DMC;
    <bullet> 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;
    <bullet> Identify and disclose any concurrent service of any DMC 
member on other DMCs of the same, related, or competing products;
    <bullet> 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
    <bullet> 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 (Sec.  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 (Sec.  312.32) and 
unanticipated adverse device effects in the case of device trials 
(Sec.  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 
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

[[Page 23731]]

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 Drugs Evaluation and 
Research, and the Center for Devices and Radiological Health. FDA 
estimates that the average length of a clinical trial is 2 years, 
resulting in an annual estimate of 370 clinical trials. Because FDA has 
no information on which to project a change in the use of DMCs, FDA 
estimates that the number of clinical trials with DMCs will not change 
significantly in the next few years. 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 December 22, 2011 (76 FR 79689), 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      Number of     responses per   Total annual   Average burden    Total hours
            activity                respondents     respondent       responses     per response
----------------------------------------------------------------------------------------------------------------
5. Sponsor reporting to FDA on                37               1              37            0.50            18.5
 DMC recommendations related to                                                     (30 minutes)
 safety.........................
                                 -------------------------------------------------------------------------------
    Total.......................  ..............  ..............  ..............  ..............            18.5
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.


                                Table 2--Estimated Annual Recordkeeping Burden 1
----------------------------------------------------------------------------------------------------------------
                                                     Number of                    Average burden
     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
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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
----------------------------------------------------------------------------------------------------------------
                                                     Number of
  Section of guidance/reporting      Number of     responses per   Total annual   Average burden    Total hours
            activity                respondents     respondent       responses     per response
----------------------------------------------------------------------------------------------------------------
4.4.1.2. Sponsor notification to               1               1               1            0.25            0.25
 the DMC regarding waivers......                                                    (15 minutes)
4.4.3.2. DMC reports of meeting              370               2             740               1             740
 minutes to the sponsor.........
                                 -------------------------------------------------------------------------------
    Total.......................  ..............  ..............  ..............  ..............          740.25
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.



[[Page 23732]]

    Dated: April 16, 2012.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2012-9533 Filed 4-19-12; 8:45 am]
BILLING CODE 4160-01-P


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