80 FR 54297 - 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
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration Federal Register Volume 80, Issue 174 (September 9, 2015)
Food and Drug Administration
Federal Register Volume 80, Issue 174 (September 9, 2015)
| Page Range | 54297-54299 | |
| FR Document | 2015-22680 |
[Federal Register Volume 80, Number 174 (Wednesday, September 9, 2015)] [Notices] [Pages 54297-54299] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2015-22680] ----------------------------------------------------------------------- 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. ----------------------------------------------------------------------- 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 [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: FDA PRA Staff, Office of Operations, Food and Drug Administration, 8455 Colesville Rd., COLE-14526, Silver Spring, MD 20993-0002, [email protected]. 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; [[Page 54298]] 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\ -------------------------------------------------------------------------------------------------------------------------------------------------------- Number of Section of guidance/reporting activity Number of responses per Total annual Average burden per response Total hours respondents respondent responses -------------------------------------------------------------------------------------------------------------------------------------------------------- 5. Sponsor reporting to FDA on DMC 37 1 37 0.5 (30 min.)......................... 18.5 recommendations related to safety. -------------------------------------------------------------------------------------------------------------------------------------------------------- \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\ -------------------------------------------------------------------------------------------------------------------------------------------------------- Number of Section of guidance/recordkeeping activity Number of records per Total annual Average burden per recordkeeping Total hours recordkeepers recordkeeper records -------------------------------------------------------------------------------------------------------------------------------------------------------- 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 Number of disclosures Total annual Section of guidance/disclosure activity respondents per disclosures Average burden per disclosure Total hours respondent -------------------------------------------------------------------------------------------------------------------------------------------------------- 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. --------------------------------------------------------------------------------------------------------- Total..................................... .............. .............. .............. ........................................ 740.25 -------------------------------------------------------------------------------------------------------------------------------------------------------- \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
![Federal Register / Vol. 80, No. 174 / Wednesday, September 9, 2015 / Notices 54297
disputes related to an application for a Dated: September 2, 2015. and devices (21 CFR 312.50 and 312.56
user fee product under any of the Leslie Kux, for drugs and biologics and 21 CFR
available regulatory mechanisms (i.e., Associate Commissioner for Policy. 812.40 and 812.46 for devices). Various
21 CFR 10.75, 312.48(c), 314.103(c)), [FR Doc. 2015–22678 Filed 9–8–15; 8:45 am] individuals and groups play different
through the formal dispute resolution BILLING CODE 4164–01–P roles in clinical trial monitoring. One
process. such group is a data monitoring
committee (DMC), appointed by a
This revised draft guidance is being
DEPARTMENT OF HEALTH AND sponsor to evaluate the accumulating
issued consistent with FDA’s good outcome data in some trials. A clinical
HUMAN SERVICES
guidance practices regulation (21 CFR trial DMC is a group of individuals with
10.115). The draft guidance, when Food and Drug Administration pertinent expertise that reviews on a
finalized, will represent the current regular basis accumulating data from
[Docket No. FDA–2011–N–0908]
thinking of FDA on formal dispute one or more ongoing clinical trials. The
resolution requests for appeals above Agency Information Collection DMC advises the sponsor regarding the
the division level. It does not establish Activities; Submission for Office of continuing safety of current trial
any rights for any person and is not Management and Budget Review; subjects and those yet to be recruited to
binding on FDA or the public. You can Comment Request; Guidance for the trial, as well as the continuing
use an alternative approach if it satisfies Clinical Trial Sponsors: Establishment validity and scientific merit of the trial.
the requirements of the applicable and Operation of Clinical Trial Data The guidance document referenced in
statutes and regulations. Monitoring Committees this document is intended to assist
AGENCY: Food and Drug Administration, sponsors of clinical trials in determining
II. The Paperwork Reduction Act of
HHS. when a DMC is needed for monitoring
1995
a study, and how such committees
ACTION: Notice.
This revised draft guidance refers to should operate. The guidance addresses
previously approved collections of SUMMARY: The Food and Drug the roles, responsibilities, and operating
information that are subject to review by Administration (FDA) is announcing procedures of DMCs, describes certain
the Office of Management and Budget that a proposed collection of reporting and recordkeeping
(OMB) under the Paperwork Reduction information has been submitted to the responsibilities, including the
Office of Management and Budget following: (1) Sponsor reporting to FDA
Act of 1995 (44 U.S.C. 3501–3520). The
(OMB) for review and clearance under on DMC recommendations related to
collections of information in this draft
the Paperwork Reduction Act of 1995. safety; (2) standard operating
guidance have been approved under procedures (SOPs) for DMCs; (3) DMC
OMB control number 0910–0430. This DATES: Fax written comments on the
collection of information by October 9, meeting records; (4) sponsor notification
draft guidance is a revision of an earlier to the DMC regarding waivers; and (5)
2015.
version of the guidance. The revised DMC reports based on meeting minutes
ADDRESSES: To ensure that comments on
version contains no additional to the sponsor.
information collections; therefore, it the information collection are received,
OMB recommends that written 1. Sponsor Reporting to FDA on DMC
continues to be covered under OMB
comments be faxed to the Office of Recommendations Related to Safety
control number 0910–0430.
Information and Regulatory Affairs,
III. Comments OMB, Attn: FDA Desk Officer, FAX: The requirement of the sponsor to
202–395–7285, or emailed to oira_ report DMC recommendations related to
Interested persons may submit either submission@omb.eop.gov. All serious adverse events in an expedited
electronic comments regarding this comments should be identified with the manner in clinical trials of new drugs
document to http://www.regulations.gov OMB control number 0910–0581. Also (21 CFR 312.32(c)) would not apply
or written comments to the Division of include the FDA docket number found when the DMC recommendation is
Dockets Management (see ADDRESSES). It in brackets in the heading of this related to an excess of events not
is only necessary to send one set of document. classifiable as serious. Nevertheless, the
comments. Identify comments with the Agency recommends in the guidance
FOR FURTHER INFORMATION CONTACT: FDA
docket number found in brackets in the that sponsors inform FDA about all
PRA Staff, Office of Operations, Food recommendations related to the safety of
heading of this document. Received and Drug Administration, 8455 the investigational product whether or
comments may be seen in the Division Colesville Rd., COLE–14526, Silver not the adverse event in question meets
of Dockets Management between 9 a.m. Spring, MD 20993–0002, PRAStaff@ the definition of ‘‘serious.’’
and 4 p.m., Monday through Friday, and fda.hhs.gov.
will be posted to the docket at http:// SUPPLEMENTARY INFORMATION: In
2. SOPs for DMCs
www.regulations.gov. compliance with 44 U.S.C. 3507, FDA In the guidance, FDA recommends
IV. Electronic Access has submitted the following proposed that sponsors establish procedures to do
collection of information to OMB for the following things:
Persons with access to the Internet review and clearance. • Assess potential conflicts of interest
may obtain the document at http:// Guidance for Clinical Trial Sponsors: of proposed DMC members;
www.fda.gov/Drugs/ Establishment and Operation of • Ensure that those with serious
Lhorne on DSK5TPTVN1PROD with NOTICES
GuidanceCompliance Clinical Trial Data Monitoring conflicts of interest are not included in
RegulatoryInformation/Guidances/ Committees the DMC;
default.htm, http://www.fda.gov/ • Provide disclosure to all DMC
BiologicsBloodVaccines/ OMB Control Number 0910–0581— members of any potential conflicts that
GuidanceCompliance Extension are not thought to impede objectivity
RegulatoryInformation/default.htm, or Sponsors are required to monitor and, thus, would not preclude service
http://www.regulations.gov. studies evaluating new drugs, biologics, on the DMC;
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![Federal Register / Vol. 80, No. 174 / Wednesday, September 9, 2015 / Notices 54299
TABLE 2—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1
Number of
Number of Total annual Average burden
Section of guidance/recordkeeping activity records per Total hours
recordkeepers records per recordkeeping
recordkeeper
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
Number of disclosures Total annual Average burden
Section of guidance/disclosure activity Total hours
respondents per disclosures per disclosure
respondent
4.4.1.2. Sponsor notification to the DMC regarding 1 1 1 0.25 (15 minutes) .. 0.25
waivers.
4.4.3.2. DMC reports of meeting minutes to the spon- 370 2 740 1 ............................ 740
sor.
Total ...................................................................... ........................ ........................ ........................ ............................... 740.25
1 There are no capital costs or operating and maintenance costs associated with this collection of information.
Dated: September 3, 2015. prevention and care of HIV disease and selected from prominent community
Leslie Kux, AIDS. The functions of the Council are leaders with particular expertise in, or
Associate Commissioner for Policy. solely advisory in nature. knowledge of, matters concerning HIV
[FR Doc. 2015–22680 Filed 9–8–15; 8:45 am] DATES: All nominations must be and AIDS, public health, global health,
BILLING CODE 4164–01–P received no later than 5:00 p.m. (ET) on philanthropy, marketing or business, as
October 9, 2015 at the address listed well as other national leaders held in
below. high esteem from other sectors of
DEPARTMENT OF HEALTH AND society. Council members are appointed
ADDRESSES: All nominations should be
HUMAN SERVICES by the Secretary or designee, in
mailed or delivered to Ms. B. Kaye
consultation with the White House
Nominations to the Presidential Hayes, Executive Director, PACHA,
Office on National AIDS Policy.
Advisory Council on HIV/AIDS Department of Health and Human
Pursuant to advance written agreement,
Services, Office of HIV/AIDS and
AGENCY: Department of Health and Council members shall receive no
Infectious Disease Policy, 200
Human Services, Office of the Secretary, stipend for the advisory service they
Independence Avenue SW., Room 443–
Office of the Assistant Secretary for render as members of PACHA. However,
H, Washington, DC 20201.
Health. as authorized by law and in accordance
FOR FURTHER INFORMATION CONTACT: Ms. with federal travel regulations, PACHA
ACTION: Notice. Caroline Talev, Public Health Analyst, members may receive per diem and
SUMMARY: The Office of the Assistant Presidential Advisory Council on HIV/ reimbursement for travel expenses
Secretary for Health (OASH) is seeking AIDS, Department of Health and Human incurred in relation to performing duties
nominations of qualified individuals to Services, 200 Independence Avenue for the Council.
be considered for appointment as SW., Room 443–H, Hubert H. Humphrey This announcement is to solicit
members of the Presidential Advisory Building, Washington, DC 20201; (202) nominations of qualified candidates to
Council on HIV/AIDS (PACHA). The 205–1178. More detailed information fill current vacancies on the PACHA.
PACHA is a federal advisory committee about PACHA can be obtained by Nominations: In accordance with the
within the Department of Health and accessing the Council’s page at the PACHA charter, persons nominated for
Human Services (HHS). Management AIDS.gov Web site at www.aids.gov/ appointment as members of the PACHA
support for the activities of this Council pacha. should be among prominent community
is the responsibility of the OASH. The SUPPLEMENTARY INFORMATION: PACHA leaders and authorities with particular
qualified individuals will be nominated was established by Executive Order expertise in, or knowledge of, matters
to the Secretary of Health and Human 12963, dated June 14, 1995, as amended concerning HIV and AIDS, public
Services for consideration for by Executive Order 13009, dated June health, global health, philanthropy,
appointment as members of the PACHA. 14, 1996. The Council was established marketing or business, as well as other
Members of the Council, including the to provide advice, information, and national leaders held in high esteem
Chair, are appointed by the Secretary. recommendations to the Secretary from other sectors of society. The
Lhorne on DSK5TPTVN1PROD with NOTICES
Members are invited to serve on the regarding programs and policies following information should be
Council for up to four-year terms. The intended to promote effective included in the package of material
Council was established to provide prevention and care of HIV disease and submitted for each individual being
advice, information, and AIDS. The functions of the Council are nominated for consideration of
recommendations to the Secretary solely advisory in nature. appointment:
regarding programs and policies The Council consists of not more than • Name, return address, daytime
intended to promote effective 25 members. Council members are telephone number, and affiliation(s) of
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Document Created: 2015-12-15 09:53:03
Document Modified: 2015-12-15 09:53:03
| Category | Regulatory Information | |
| Collection | Federal Register | |
| sudoc Class | AE 2.7: GS 4.107: AE 2.106: | |
| Publisher | Office of the Federal Register, National Archives and Records Administration | |
| Section | Notices | |
| Action | Notice. | |
| Dates | Fax written comments on the collection of information by October 9, 2015. | |
| Contact | FDA PRA Staff, Office of Operations, Food and Drug Administration, 8455 Colesville Rd., COLE-14526, Silver Spring, MD 20993-0002, [email protected] | |
| FR Citation | 80 FR 54297 |
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