[Federal Register Volume 70, Number 250 (Friday, December 30, 2005)]
[Notices]
[Pages 77403-77405]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E5-8115]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2001D-0489] (formerly Docket No. 01D-0489)


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Draft Guidance for 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 January 
30, 2005.

ADDRESSES: OMB is still experiencing significant delays in the regular 
mail, including first class and express mail, and messenger deliveries 
are not being accepted. 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: Fumie 
Yokota, Desk Officer for FDA, FAX: 202-395-6974.
    Submit written requests for single copies of the draft guidance 
dated December 2005 to the Office of Communication, Training, and 
Manufacturers Assistance (HFM-40), Center for Biologics Evaluation and 
Research (CBER), Food and Drug Administration, 1401 Rockville Pike, 
Rockville, MD 20852-1448. Send one self-addressed adhesive label to 
assist the office in processing your requests. The draft guidance may 
also be obtained by mail by calling CBER at 1-800-835-4709 or 301-827-
1800. Persons with access to the Internet may obtain the draft guidance 
at either http://www.fda.gov/cber/guidelines.htm or http://www.fda.gov/ohrms/dockets/default.htm.

FOR FURTHER INFORMATION CONTACT: Jonna Capezzuto, Office of Management 
Programs (HFA-250), Food and Drug Administration, 5600 Fishers Lane, 
Rockville, MD 20857, 301-827-4659.

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.

Draft Guidance for Clinical Trial Sponsors: Establishment and Operation 
of Clinical Trial Data Monitoring Committees

    The draft guidance document, when finalized, is intended to assist 
sponsors of clinical trials in determining when a Data Monitoring 
Committee (DMC) is needed for study monitoring, and how such committees 
should operate. The draft guidance was revised based on public 
comments. The draft 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 of expedited reporting, (2) 
DMC reports of meeting minutes to the sponsor, (3) sponsor reporting to 
FDA on DMC safety-related recommendations, (4) standard operating 
procedures (SOPs) for DMCs, (5) DMC meeting records, and (6) DMC 
reports to the sponsor.

A. Sponsor Notification to the DMC Regarding Waivers

    The sponsor has the responsibility of reporting to FDA serious, 
unexpected adverse events in drugs and biologics trials under part 312 
(21 CFR part 312) in Sec.  312.32 and unanticipated adverse events in 
the case of device trials under part 812 (21 CFR part 812) in Sec.  
812.150(b)(1). We recommend in the draft guidance that sponsors notify 
DMCs about any waivers granted by FDA for expedited reporting of 
certain serious events.

B. DMC Report of Meeting Minutes to the Sponsor

    FDA recommends in the draft guidance that the DMC issue a written 
report to the sponsor based on the 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.

C. Sponsor reporting to FDA on DMC Safety-Related Recommendations

    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

[[Page 77404]]

serious. Nevertheless, we recommend in the draft 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.''

D. Standard Operating Procedures

    In the draft 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 on 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 are associated with such 
arrangements, if the primary study statistician takes on the 
responsibility for interim analysis and reporting to the DMC, and it 
appears infeasible or highly impractical for any other statistician to 
take over responsibilities related to trial management.

E. Meeting Records

    FDA recommends in the draft 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 revised draft 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 
revised draft guidance.
    Based on information from FDA review divisions, FDA estimates there 
are currently 740 clinical trials with DMCs regulated by CBER, 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 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 draft 
guidance recommends them, FDA estimates that the majority of sponsors 
have already prepared SOPs for DMCs, and only a minimum amount of time 
would be 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 the 
meeting minutes to the sponsor. One set of both of the 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 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.
    In the Federal Register of November 20, 2001 (FR 66 58151), FDA 
published a 60-day notice requesting public comment on the information 
collection provisions in the draft guidance. FDA received a number of 
comments on the draft guidance, however, only one letter of comment 
included comments regarding the information collection provisions.
    The comment stated that the ``Hours per Response'' were 
underestimated for the SOPs and Data Analysis Plan (statistical 
approach) listed in table 1 of the 60-day notice (66 FR 58151 at 58153) 
for the ``Estimated Annual Reporting Burden.'' The comment requested an 
increase to 12 hours for these burdens from the previous estimate of 4 
hours for the SOPs, and 8 hours for the Data Analysis Plan.
    In revising the draft guidance, FDA is adding the applicable 
regulations throughout the draft guidance including the regulations 
associated with these two burden estimates. The burden associated with 
the submission of SOPs and the statistical approach in table 1 of the 
60-day notice is covered under Sec. Sec.  312.23 and 812.150(b)(10) and 
is approved under OMB Control Nos. 0910-0014 and 0910-0078. Therefore, 
these categories were removed from table 1 and no change in the burden 
estimates is necessary.
    Based on revisions to the draft guidance, however, two additional 
information collection burdens have been added to table 1 of this 
document, and one additional previous information collection burden was 
deleted from table 1 of the 60-day notice.
    The information collection provisions in the draft guidance for 
Sec. Sec.  312.30, 312.32, 312.38, 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 and 
812.150 have been approved under OMB Control No. 0190-0078.
    The total estimated burden for both the reporting and recordkeeping 
burdens under the draft guidance are 1,794.75 hours.

                                 Table 1.--Estimated Annual Reporting Burden\1\
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Section of Draft
    Guidance/           No. of         Annual Frequency       Total Annual        Hours per
    Reporting        Respondents         per Response          Responses          Response         Total Hours
    Activity
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4.4.1.2 Sponsor                   1                     1                  1               .25               .25
 notification to
 the DMC
 regarding
 waivers of
 expedited
 reporting
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[[Page 77405]]

 
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Total                                                                                                     758.75
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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\
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   Reporting          No. of         Annual Frequency       Total Annual
   Activity       Recordkeepers      per Recordkeeping        Records       Hours per  Record     Total Hours
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4.1 and 6.4                    37                     1                 37                  8                296
 SOPs for DMCs
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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.


    Dated: December 22, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E5-8115 Filed 12-29-05; 8:45 am]
BILLING CODE 4160-01-S