80 FR 16402 - Agency Information Collection Activities; Proposed Collection; 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 59 (March 27, 2015)
Food and Drug Administration
Federal Register Volume 80, Issue 59 (March 27, 2015)
| Page Range | 16402-16405 | |
| FR Document | 2015-07009 |
[Federal Register Volume 80, Number 59 (Friday, March 27, 2015)] [Notices] [Pages 16402-16405] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2015-07009] ----------------------------------------------------------------------- DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0908] Agency Information Collection Activities; Proposed Collection; 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 an opportunity for public comment on the proposed collection of certain information by the Agency. Under the Paperwork Reduction Act of 1995 (the PRA), Federal Agencies are required to publish notice in the Federal Register concerning each proposed collection of information, including each proposed extension of an existing collection of information and to allow 60 days for public comment in response to the notice. This notice solicits comments on the collection of information concerning the establishment and operation of clinical trial data monitoring committees. [[Page 16403]] DATES: Submit either electronic or written comments on the collection of information by May 26, 2015. ADDRESSES: Submit electronic comments on the collection of information to http://www.regulations.gov. Submit written comments on the collection of information to the Division of Dockets Management (HFA- 305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. All comments should be identified with the 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: Under the PRA (44 U.S.C. 3501-3520), Federal Agencies must obtain approval from the Office of Management and Budget (OMB) for each collection of information they conduct or sponsor. ``Collection of information'' is defined in 44 U.S.C. 3502(3) and 5 CFR 1320.3(c) and includes Agency requests or requirements that members of the public submit reports, keep records, or provide information to a third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A)) requires Federal Agencies to provide a 60-day notice in the Federal Register concerning each proposed collection of information, including each proposed extension of an existing collection of information, before submitting the collection to OMB for approval. To comply with this requirement, FDA is publishing notice of the proposed collection of information set forth in this document. With respect to the following collection of information, FDA invites comments on these topics: (1) Whether the proposed collection of information is necessary for the proper performance of FDA's functions, including whether the information will have practical utility; (2) the accuracy of FDA's estimate of the burden of the proposed collection of information, including the validity of the methodology and assumptions used; (3) ways to enhance the quality, utility, and clarity of the information to be collected; and (4) ways to minimize the burden of the collection of information on respondents, including through the use of automated collection techniques, when appropriate, and other forms of information technology. 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 (section 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: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 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 (section 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 (section 312.32) and unanticipated adverse device effects in the case of device trials (section 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 [[Page 16404]] 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 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 No. 0910-0014; 21 CFR 314.50 has been approved under OMB Control No. 0910-0001; and 21 CFR 812.35 and 812.150 have been approved under OMB Control No. 0910-0078. 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 Total hours respondents respondent responses per response -------------------------------------------------------------------------------------------------------------------------------------------------------- 5. Sponsor reporting to FDA on DMC recommendations related 37 1 37 0.50 (30 min.) 18.5 to safety.................................................. -------------------------------------------------------------------------------------------------------------------------------------------------------- \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 Section of guidance/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 -------------------------------------------------------------------------------------------------------------------------------------------------------- \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/disclosure activity Number of disclosures per Total annual Average burden Total hours respondents respondent disclosures per disclosure -------------------------------------------------------------------------------------------------------------------------------------------------------- 4.4.1.2. Sponsor notification to the DMC regarding waivers...... 1 1 1 0.25 0.25 (15 minutes) 4.4.3.2. DMC reports of meeting minutes to the sponsor.......... 370 2 740 1 740 --------------------------------------------------------------------------------------- Total....................................................... ................ ................ ............... ............... 740.25 -------------------------------------------------------------------------------------------------------------------------------------------------------- \1\ There are no capital costs or operating and maintenance costs associated with this collection of information. [[Page 16405]] Dated: March 23, 2015. Leslie Kux, Associate Commissioner for Policy. [FR Doc. 2015-07009 Filed 3-26-15; 8:45 am] BILLING CODE 4164-01-P
![16402 Federal Register / Vol. 80, No. 59 / Friday, March 27, 2015 / Notices
(Ebola). Ebola is a type of viral a person with Ebola while the person restricted as a result of placement on the
hemorrhagic fever that is often fatal in was showing symptoms DNB list and associated Lookout records
humans and nonhuman primates. Ebola • In countries with widespread Ebola may submit a written response to the
can spread through human-to-human virus transmission: Direct contact Director, Division of Global Migration
transmission, with infection resulting while using appropriate PPE with a and Quarantine, if they believe that
from direct contact (through broken skin person with Ebola while the person HHS/CDC has erred in its public health
or mucous membranes) with the blood, was showing symptoms, or with the request to DHS. The response should be
secretions, droplets, or other body fluids person’s body fluids, or any direct addressed to: Director, Division of
of infected people, and indirectly from patient care in other healthcare Global Migration and Quarantine,
contact with surfaces or items (such as settings ATTN: Travel Restriction and
needles) contaminated with such fluids. • Close contact in households, Intervention Activity, Centers for
With respect to viral hemorrhagic healthcare facilities, or community Disease Control and Prevention, 1600
fevers, placement on the DNB list and settings with a person with Ebola Clifton Road, MS E–03, Atlanta, GA
associated Lookout record is requested while the person was showing 30329. Responses may also be faxed to
for people known or suspected to have symptoms CDC at (404) 718–2158 or emailed to
a viral hemorrhagic fever. Placement Æ Close contact is defined as not travelrestrictions@cdc.gov.
may also be requested for people wearing appropriate PPE within As part of the response, individuals
without symptoms who have been approximately 3 feet (1 meter) of a should include the reference number
exposed to a viral hemorrhagic fever, person with Ebola while the person listed in the notification letter they
particularly if these individuals intend was showing symptoms received and any facts or other evidence
to travel against public health • Having brief direct contact (e.g.,
indicating why they believe that HHS/
recommendations. Even though people shaking hands), while not wearing
CDC’s public health request was made
without symptoms are not infectious, appropriate PPE, with a person with
in error.
these restrictions are requested because Ebola while the person was in the
The policy and program operations
of the possibility that symptoms could early stage of disease
• In countries without widespread described above will become effective
develop during travel, particularly long on March 27, 2015.
international flights. Exposure is Ebola virus transmission: Direct
determined through a CDC risk factor contact while using appropriate PPE Dated: March 24, 2015.
assessment using information available with a person with Ebola while the Sylvia M. Burwell,
from a variety of public health, medical person was showing symptoms Secretary.
and other official sources. Examples of • Traveled on an aircraft with a person [FR Doc. 2015–07118 Filed 3–26–15; 8:45 am]
types of potential exposure to viral with Ebola while the person was BILLING CODE 4163–18–P
hemorrhagic fevers contained within the showing symptoms
CDC risk factor assessment include the Exposure risk factors, such as those just
following. It should be noted that not all described, will be considered by HHS/ DEPARTMENT OF HEALTH AND
of these exposures may result in travel CDC in their totality when determining HUMAN SERVICES
restrictions. whether an individual meets the first
• Having been in a country with criteria for placement on the DNB List, Food and Drug Administration
widespread Ebola virus transmission as described in Section I of this notice. [Docket No. FDA–2011–N–0908]
within the past 21 days and, although HHS/CDC would also consider other
having had no known exposures, is facts and information it may have to Agency Information Collection
showing symptoms make a decision with respect to the Activities; Proposed Collection;
• Percutaneous (e.g., needle stick) or other criteria, as described in Section I Comment Request; Guidance for
mucous membrane exposure to blood of this notice. It should be noted that all Clinical Trial Sponsors: Establishment
or body fluids of a person with Ebola facts are considered when applying the and Operation of Clinical Trial Data
while the person was showing criteria. Again, with the exception of the Monitoring Committees
symptoms first criteria, not all of the other criteria
• Exposure to the blood or body fluids need to be present for HHS/CDC to AGENCY: Food and Drug Administration,
(including but not limited to feces, make a request to DHS to have an HHS.
saliva, sweat, urine, vomit, and individual placed on DNB and Lookout. ACTION: Notice.
semen) of a person with Ebola while HHS/CDC would also consider these
the person was showing symptoms risk factors when assessing an SUMMARY: The Food and Drug
without appropriate personal individual who has been in a country Administration (FDA) is announcing an
protective equipment (PPE) (see where outbreaks of viral hemorrhagic opportunity for public comment on the
http://www.cdc.gov/vhf/ebola/hcp/ fevers were occurring and refuses to proposed collection of certain
procedures-for-ppe.html) comply with a public health assessment, information by the Agency. Under the
• Laboratory processing of blood or and otherwise meets the travel Paperwork Reduction Act of 1995 (the
body fluids of a person with Ebola restriction criteria. Refusing to comply PRA), Federal Agencies are required to
while the person was showing with a public health risk assessment in publish notice in the Federal Register
symptoms without appropriate PPE or this situation could include refusing to concerning each proposed collection of
standard biosafety protections provide relevant information that would information, including each proposed
• Direct contact with a dead body
mstockstill on DSK4VPTVN1PROD with NOTICES
allow public health officials to assess extension of an existing collection of
without appropriate PPE in a country the exposure risk. information and to allow 60 days for
with widespread Ebola virus public comment in response to the
transmission (see http://www.cdc.gov/ V. Provisions of This Notice notice. This notice solicits comments on
vhf/ebola/outbreaks/2014-west-africa/ HHS/CDC will make requests of DHS the collection of information concerning
distribution-map.html) based on the criteria in this notice the establishment and operation of
• Having lived in the immediate effective immediately. Individuals who clinical trial data monitoring
household and provided direct care to have had their travel temporarily committees.
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![Federal Register / Vol. 80, No. 59 / Friday, March 27, 2015 / Notices 16405
Dated: March 23, 2015. Prevention, 1600 Clifton Road NE., MS– provide information to or for a Federal
Leslie Kux, D74, Atlanta, Georgia 30329. agency. This includes the time needed
Associate Commissioner for Policy. Instructions: All submissions received to review instructions; to develop,
[FR Doc. 2015–07009 Filed 3–26–15; 8:45 am] must include the agency name and acquire, install and utilize technology
BILLING CODE 4164–01–P
Docket Number. All relevant comments and systems for the purpose of
received will be posted without change collecting, validating and verifying
to Regulations.gov, including any information, processing and
DEPARTMENT OF HEALTH AND personal information provided. For maintaining information, and disclosing
HUMAN SERVICES access to the docket to read background and providing information; to train
documents or comments received, go to personnel and to be able to respond to
Centers for Disease Control and Regulations.gov. a collection of information, to search
Prevention Please note: All public comment data sources, to complete and review
should be submitted through the the collection of information; and to
[60Day–15–15UX: Docket No. CDC–2015– Federal eRulemaking portal transmit or otherwise disclose the
0011]
(Regulations.gov) or by U.S. mail to the information.
Proposed Data Collection Submitted address listed above.
Proposed Project
for Public Comment and FOR FURTHER INFORMATION CONTACT: To
Recommendations request more information on the Continuing and New International
proposed project or to obtain a copy of and U.S. Data Collections from the 2014
AGENCY: Centers for Disease Control and the information collection plan and CDC Ebola Virus Disease Emergency
Prevention (CDC), Department of Health instruments, contact the Information Response—New—National Center for
and Human Services (HHS). Collection Review Office, Centers for Emerging and Zoonotic Infectious
ACTION: Notice with comment period. Disease Control and Prevention, 1600 Diseases (NCEZID), Centers for Disease
Clifton Road NE., MS–D74, Atlanta, Control and Prevention (CDC).
SUMMARY: The Centers for Disease Georgia 30329; phone: 404–639–7570;
Control and Prevention (CDC), as part of Background and Brief Description
Email: omb@cdc.gov.
its continuing efforts to reduce public SUPPLEMENTARY INFORMATION: Under the The international outbreak of Ebola
burden and maximize the utility of Paperwork Reduction Act of 1995 (PRA) virus disease (EVD) in West Africa
government information, invites the (44 U.S.C. 3501–3520), Federal agencies began March 10, 2014. The initial cases
general public and other Federal must obtain approval from the Office of were from southern Guinea, near its
agencies to take this opportunity to Management and Budget (OMB) for each rural border with Liberia and Sierra
comment on proposed and/or collection of information they conduct Leone. Highly mobile populations
continuing information collections, as or sponsor. In addition, the PRA also contributed to increasing waves of
required by the Paperwork Reduction requires Federal agencies to provide a person-to-person transmission of EVD
Act of 1995. This notice invites 60-day notice in the Federal Register that occurred in multiple countries in
comment on ‘‘Continuing and New concerning each proposed collection of West Africa. The Centers for Disease
International and U.S. Data Collections information, including each new Control and Prevention (CDC)
from the 2014 CDC Ebola Virus Disease proposed collection, each proposed Emergency Operations Center (EOC)
Emergency Response’’. Under the extension of existing collection of was activated on July 9, 2014, to help
current 60-day Federal Register Notice, information, and each reinstatement of coordinate technical assistance and
the CDC is announcing its intention to previously approved information control activities with international
seek three-year OMB approval to collection before submitting the partners and to deploy teams of public
continue several Ebola-related collection to OMB for approval. To health experts to the affected countries.
information collections beyond their comply with this requirement, we are The operations turned to the United
current emergency expiration dates and publishing this notice of a proposed States (U.S.) when the first imported
to conduct newly proposed information data collection as described below. case of EVD was diagnosed in Texas on
collections within international borders Comments are invited on: (a) Whether September 30, 2014. In response, on
of Ebola-affected West African countries the proposed collection of information October 11, 2014, the CDC Quarantine
and within the domestic borders of is necessary for the proper performance Stations and the Department of
State, Territorial and Local (STL) public of the functions of the agency, including Homeland Security (DHS) Customs and
health authorities in the U.S. These whether the information shall have Border Patrol (CBP) mobilized to screen,
existing ‘‘source’’ information practical utility; (b) the accuracy of the detect, and refer arriving travelers who
collections and new information agency’s estimate of the burden of the were potential persons at risk for EVD
collection requests (ICRs) will be proposed collection of information; (c) to appropriate state, territorial, and local
submitted under four ‘‘destination’’ ways to enhance the quality, utility, and (STL) authorities. The CDC also
ICRs for Office of Management and clarity of the information to be increased its commitment to support
Budget (OMB) approval. collected; (d) ways to minimize the STL public health authorities to combat
DATES: Written comments must be burden of the collection of information and control the spread of EVD within
received on or before May 26, 2015. on respondents, including through the their jurisdictions.
ADDRESSES: You may submit comments, use of automated collection techniques Thus in 2014, the CDC used OMB
mstockstill on DSK4VPTVN1PROD with NOTICES
identified by Docket No. CDC–2015– or other forms of information emergency clearance procedures to
0011, by any of the following methods: technology; and (e) estimates of capital initiate and expedite multiple urgently
• Federal eRulemaking Portal: or start-up costs and costs of operation, needed information collections in West
Regulation.gov. Follow the instructions maintenance, and purchase of services Africa, at U.S. ports of entry, and within
for submitting comments. to provide information. Burden means STL jurisdictions. These procedures
• Mail: Leroy A. Richardson, the total time, effort, or financial allowed the agency to accomplish its
Information Collection Review Office, resources expended by persons to primary mission on many fronts to
Centers for Disease Control and generate, maintain, retain, disclose or quickly prevent public harm, illness,
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Document Created: 2015-12-18 11:36:53
Document Modified: 2015-12-18 11:36:53
| 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 | Submit either electronic or written comments on the collection of information by May 26, 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 16402 |
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