[Federal Register Volume 74, Number 45 (Tuesday, March 10, 2009)]
[Notices]
[Pages 10253-10255]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-4971]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2008-N-0521]


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.

-----------------------------------------------------------------------

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 April 
9, 2009.

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: 202-395-6974, or e-mailed to [email protected]. 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: Jonna Capezzuto,Office of Information 
Management (HFA-710), Food and Drug Administration, 5600 Fishers Lane, 
Rockville, MD 20857, 301-796-3794.

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.

[[Page 10254]]

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 an ongoing clinical trial. The DMC advises the sponsor regarding 
the continuing safety of current participants and those yet to be 
recruited, as well as the continuing validity and scientific merit of 
the trial.
    FDA's guidance 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 notification to the DMC regarding waivers, (2) 
DMC reports of meeting minutes to the sponsor, (3) sponsor reports to 
FDA on DMC recommendations related to safety, (4) standard operating 
procedures (SOPs) for DMCs, and (5) DMC meeting records.
1. Sponsor Notification to the DMC Regarding Waivers
    The sponsor must report to FDA serious unexpected adverse events in 
drugs and biologics trials (Sec.  312.32 (21 CFR 312.32)) and 
unanticipated adverse events in the case of device trials under (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.
2. DMC Reports of Meeting Minutes to the Sponsor
    The agency recommends in the guidance that the DMC 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.
3. 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)) 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.''
4. SOPs for DMCs
    In the guidance, we recommend 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 study 
statistician takes on the responsibility for interim analysis and 
reporting to the DMC; and
     Minimize the risks of bias that arise when the primary 
study 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.
5. 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))).
    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.
Reporting and Recordkeeping 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 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. 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. 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 meeting records should be maintained 
per clinical trial.
    The ``Hours per Response'' and ``Hours per Record'' are based on 
FDA's experience with comparable recordkeeping and reporting provisions 
applicable to FDA regulated industry. The ``Hours per Response'' 
include the time the respondent would spend reviewing, gathering, and 
preparing the

[[Page 10255]]

information to be submitted to the DMC, FDA, or the sponsor. The 
``Hours per Record'' include the time to record, gather, and maintain 
the information.
    The information collection provisions in the guidance for 
Sec. Sec.  312.30 (21 CFR 312.30), 312.32, 312.38 (21 CFR 312.38), 
312.55 (21 CFR 312.55), and 312.56 have been approved under OMB control 
no. 0910-0014; Sec.  314.50 has been approved under OMB control no. 
0910-0001; and Sec. Sec.  812.35 (21 CFR 812.35) and 812.150 have been 
approved under OMB control no. 0910-0078.
    In the Federal Register of October 8, 2008 (73 FR 58970), FDA 
published a 60-day notice requesting public comment on the information 
collection provisions. No comments were received.
    FDA estimates the burden of this collection of information as 
follows:

                                                     Table 1.--Estimated Annual Reporting Burden\1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                              No. of         Annual Frequency       Total Annual        Hours Per
        Section of Guidance/Reporting Activity             Respondents         per Response          Responses           Response         Total Hours
--------------------------------------------------------------------------------------------------------------------------------------------------------
4.4.1.2. Sponsor notification to the DMC regarding                      1                     1                  1                .25                .25
 waivers
--------------------------------------------------------------------------------------------------------------------------------------------------------
4.4.3.2. DMC reports of meeting minutes to the sponsor                370                     2                740                  1                740
--------------------------------------------------------------------------------------------------------------------------------------------------------
5. Sponsor reporting to FDA on DMC recommendations                     37                     1                 37                 .5               18.5
 related to safety
--------------------------------------------------------------------------------------------------------------------------------------------------------
Total                                                                                                                                             758.75
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.


                                                   Table 2.--Estimated Annual Recordkeeping Burden\1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                              No. of         Annual Frequency       Total Annual
                Recordkeeping Activity                    Recordkeepers      per Recordkeeping        Records       Hours Per  Record     Total Hours
--------------------------------------------------------------------------------------------------------------------------------------------------------
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.


    Dated: March 3, 2009.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E9-4971 Filed 3-9-09; 8:45 am]
BILLING CODE 4160-01-S