10084 Federal Register / Vol. 89, No. 30 / Tuesday, February 13, 2024 / Notices 

Recipients are required to submit their 

Post-Expenditure Report within 6 

months of the end of the period covered 

by the report. 

The law governing the programs at 

Title XX of the Social Security Act [42 

U.S.C. 1397c] mandates states and 

territories submit to the federal 

administering office an Intended Use 

Plan and Pre-Expenditure report. These 

materials are to detail the planned use 

of funds. At the end of the fiscal year, 

the law also requires states to provide 

the federal agency with a reconciliation 

of the actual use of grant funds in the 

Post-Expenditure Report [42 U.S.C. 

1397e]. 

The forms and model plans support 

the states and territories in meeting the 

statutory requirement and provide a 

consistent set of tools for information 

collection on the grants’ use for each 

state, as well as grant wide. The state 

and territory reports are congregated 

and analyzed and, in turn, comprise the 

SSBG Annual Report. The data informs 

the program’s performance and 

efficiency measures for program impact 

and efficacy. OCS is proposing to make 

minor editorial modifications to some 

column titles in the Pre- and PostExpenditure Reports, for clarification. 

Respondents: Agencies that 

administer the SSBG at the state or 

territory level, including the 50 states; 

the District of Columbia; the 

Commonwealth of Puerto Rico; 

Massachusetts Commission for the 

Blind (M–CFB); and the territories of 

American Samoa, Guam, the U.S. Virgin 

Islands, and the Commonwealth of 

Northern Mariana Islands. 

ANNUAL BURDEN ESTIMATES

Instrument 

Total 

number of 

respondents 

Annual 

number of 

responses per 

respondent 

Average 

burden hours 

per response 

Annual 

burden 

hours 

Pre-Expenditure Report Form ......................................................................... 57 1 2 114 

Intended Use Plan ........................................................................................... 57 1 40 2,280 

Post-Expenditure Reporting Form ................................................................... 57 1 110 6,270 

Estimated Total Annual Burden Hours: .................................................... ........................ ........................ ........................ 8,664 

Authority: 42 U.S.C. 1397–1397e. 

Mary C. Jones, 

ACF/OPRE Certifying Officer. 

[FR Doc. 2024–02851 Filed 2–12–24; 8:45 am] 

BILLING CODE 4184–24–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2001–D–0219] 

Use of Data Monitoring Committees in 

Clinical Trials; Draft Guidance for 

Industry; Availability; Agency 

Information Collection Activities; 

Proposed Collection; Comment 

Request 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice of availability. 

SUMMARY: The Food and Drug 

Administration (FDA, Agency, or we) is 

announcing the availability of a draft 

guidance for industry entitled ‘‘Use of 

Data Monitoring Committees in Clinical 

Trials.’’ This guidance is intended to 

assist sponsors of clinical trials in 

determining when a data monitoring 

committee (DMC) (also known as a data 

and safety monitoring board (DSMB), a 

data and safety monitoring committee 

(DSMC), or an independent data 

monitoring committee (IDMC)) would 

be useful for trial monitoring and what 

procedures and practices should be 

considered to guide their operation. 

When finalized, this guidance will 

supersede the final guidance for clinical 

trial sponsors entitled ‘‘Establishment 

and Operation of Clinical Trial Data 

Monitoring Committees,’’ issued in 

March 2006. This draft guidance is not 

final nor is it in effect at this time. 

DATES: Submit either electronic or 

written comments on the draft guidance 

by April 15, 2024 to ensure that the 

Agency considers your comment on this 

draft guidance before it begins work on 

the final version of the guidance. 

Submit electronic or written comments 

on the proposed collection of 

information in the draft guidance by 

April 15, 2024. 

ADDRESSES: You may submit comments 

on any guidance at any time as follows: 

Electronic Submissions 

Submit electronic comments in the 

following way: 

• Federal eRulemaking Portal: 

https://www.regulations.gov. Follow the 

instructions for submitting comments. 

Comments submitted electronically, 

including attachments, to https://

www.regulations.gov will be posted to 

the docket unchanged. Because your 

comment will be made public, you are 

solely responsible for ensuring that your 

comment does not include any 

confidential information that you or a 

third party may not wish to be posted, 

such as medical information, your or 

anyone else’s Social Security number, or 

confidential business information, such 

as a manufacturing process. Please note 

that if you include your name, contact 

information, or other information that 

identifies you in the body of your 

comments, that information will be 

posted on https://www.regulations.gov. 

• If you want to submit a comment 

with confidential information that you 

do not wish to be made available to the 

public, submit the comment as a 

written/paper submission and in the 

manner detailed (see ‘‘Written/Paper 

Submissions’’ and ‘‘Instructions’’). 

Written/Paper Submissions 

Submit written/paper submissions as 

follows: 

• Mail/Hand Delivery/Courier (for 

written/paper submissions): Dockets 

Management Staff (HFA–305), Food and 

Drug Administration, 5630 Fishers 

Lane, Rm. 1061, Rockville, MD 20852. 

• For written/paper comments 

submitted to the Dockets Management 

Staff, FDA will post your comment, as 

well as any attachments, except for 

information submitted, marked and 

identified, as confidential, if submitted 

as detailed in ‘‘Instructions.’’ 

Instructions: All submissions received 

must include the Docket No. FDA– 

2001–D–0219 for ‘‘Use of Data 

Monitoring Committees in Clinical 

Trials.’’ Received comments will be 

placed in the docket and, except for 

those submitted as ‘‘Confidential 

Submissions,’’ publicly viewable at 

https://www.regulations.gov or at the 

Dockets Management Staff between 9 

a.m. and 4 p.m., Monday through 

Friday, 240–402–7500. 

• Confidential Submissions—To 

submit a comment with confidential 


lotter on DSK11XQN23PROD with NOTICES1
Federal Register / Vol. 89, No. 30 / Tuesday, February 13, 2024 / Notices 10085 

information that you do not wish to be 

made publicly available, submit your 

comments only as a written/paper 

submission. You should submit two 

copies total. One copy will include the 

information you claim to be confidential 

with a heading or cover note that states 

‘‘THIS DOCUMENT CONTAINS 

CONFIDENTIAL INFORMATION.’’ The 

Agency will review this copy, including 

the claimed confidential information, in 

its consideration of comments. The 

second copy, which will have the 

claimed confidential information 

redacted/blacked out, will be available 

for public viewing and posted on 

https://www.regulations.gov. Submit 

both copies to the Dockets Management 

Staff. If you do not wish your name and 

contact information to be made publicly 

available, you can provide this 

information on the cover sheet and not 

in the body of your comments and you 

must identify this information as 

‘‘confidential.’’ Any information marked 

as ‘‘confidential’’ will not be disclosed 

except in accordance with 21 CFR 10.20 

and other applicable disclosure law. For 

more information about FDA’s posting 

of comments to public dockets, see 80 

FR 56469, September 18, 2015, or access 

the information at: https://

www.govinfo.gov/content/pkg/FR-2015- 

09-18/pdf/2015-23389.pdf. 

Docket: For access to the docket to 

read background documents or the 

electronic and written/paper comments 

received, go to https://

www.regulations.gov and insert the 

docket number, found in brackets in the 

heading of this document, into the 

‘‘Search’’ box and follow the prompts 

and/or go to the Dockets Management 

Staff, 5630 Fishers Lane, Rm. 1061, 

Rockville, MD 20852, 240–402–7500. 

You may submit comments on any 

guidance at any time (see 21 CFR 

10.115(g)(5)). 

Submit written requests for single 

copies of this draft guidance to the 

Division of Drug Information, Center for 

Drug Evaluation and Research, Food 

and Drug Administration, 10001 New 

Hampshire Ave., Hillandale Building, 

4th Floor, Silver Spring, MD 20993– 

0002, or to the Office of 

Communication, Outreach and 

Development, Center for Biologics 

Evaluation and Research (CBER), Food 

and Drug Administration, 10903 New 

Hampshire Ave., Bldg. 71, Rm. 3128, 

Silver Spring, MD 20993–0002, or to the 

Office of Policy, Guidance and Policy 

Development, Center for Devices and 

Radiological Health, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 66, Rm. 5431, Silver Spring, 

MD 20993–0002. Send one selfaddressed adhesive label to assist that 

office in processing your requests. See 

the SUPPLEMENTARY INFORMATION section 

for information on electronic access to 

the draft guidance document. 

FOR FURTHER INFORMATION CONTACT: 

With regard to the draft guidance: Dat 

Doan, Center for Drug Evaluation and 

Research, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 51, Rm. 3334 Silver Spring, 

MD 20993, 240–402–8926; or James 

Myers, Center for Biologics Evaluation 

and Research, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 71, Rm. 7256, Silver Spring, 

MD 20993–0002, 240–402–7911; or 

Ouided Rouabhi, Center for Devices and 

Radiological Health, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 66, Rm. G221, Silver Spring, 

MD 20993–0002, 301–796–6359. 

With regard to the proposed collection 

of information: Rachel Showalter, Office 

of Operations, Food and Drug 

Administration, Three White Flint 

North, 10A–12M, 11601 Landsdown St., 

North Bethesda, MD 20852, 240–994– 

7399, PRAStaff@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a draft guidance for industry entitled 

‘‘Use of Data Monitoring Committees in 

Clinical Trials.’’ This guidance pertains 

primarily to the sponsor’s responsibility 

for clinical trial management and 

decision making, but may also be 

relevant to any individual or group to 

whom the sponsor has delegated 

applicable trial management 

responsibilities. This guidance provides 

recommendations to help sponsors of 

clinical trials determine: (1) when a 

DMC (also known as a DSMB, a DSMC, 

or an IDMC) would be useful for trial 

monitoring and (2) what procedures and 

practices should be considered to guide 

their operation. Under FDA regulations, 

sponsors are not required to use DMCs 

in clinical trials except under 21 CFR 

50.24(a)(7)(iv), where an institutional 

review board can approve a clinical trial 

without requiring informed consent 

from all research subjects, provided 

certain requirements are met, including 

the establishment of an independent 

DMC. 

Although the use of DMCs initially 

was more common in disease areas 

associated with significant morbidity or 

mortality, since 2006, there has been an 

increase in the use of DMCs in many 

disease areas not involving serious 

morbidity or mortality. For example, 

DMCs can provide the specialized 

expertise to evaluate emerging efficacy 

and safety data for trials in rare diseases 

(e.g., certain genetic disorders), for trials 

in vulnerable populations (e.g., 

neonates), and for oncologic therapies 

with highly specific targets and 

potential serious risks (e.g., biological 

products for genetic targets, 

immunotherapies). DMCs are also being 

used in early phase trials in serious 

diseases or conditions. With this growth 

of DMC use, a variety of approaches to 

DMC operations has been developed. 

This draft guidance revises the 

guidance for clinical trial sponsors 

entitled ‘‘Establishment and Operation 

of Clinical Trial Data Monitoring 

Committees’’ issued on March 28, 2006. 

Changes to the guidance reflect changes 

in DMC structure and practice since 

FDA issued the 2006 version. When 

finalized, this guidance will replace the 

2006 guidance. 

Sponsors may be required to monitor 

clinical studies evaluating 

investigational drugs, biological 

products, and devices (see 21 CFR 

312.50 and 312.56 (for drugs and 

biological products) and 21 CFR 

812.2(b)(1)(iv), 812.40, and 812.46 (for 

devices)). Various groups and/or 

individuals play different roles in 

clinical trial monitoring and oversight. 

One such group is a DMC. A clinical 

trial DMC is established by a sponsor 

and is composed of a group of 

individuals with relevant expertise that 

reviews accumulating data on a regular 

basis from one or more clinical trials 

and recommends to the sponsor 

whether to continue, modify, or stop a 

trial or trials. 

Consistent with § 312.32(d)(1) (21 

CFR 312.32(d)(1)), the sponsor must 

investigate a DMC’s recommendation 

relating to an increased rate of serious 

unanticipated adverse events as 

potentially reportable to FDA under 

§ 312.32. If the sponsor concludes that 

there is a ‘‘reasonable possibility’’ that 

the increased rate of serious 

unanticipated adverse events was 

associated with use of the drug, the 

finding, and support for it (which could 

include the DMC report, any analyses, 

and pertinent data) must be submitted 

to FDA as a serious unexpected 

suspected adverse reaction. Similar 

considerations would also apply if the 

sponsor concludes that an increased rate 

of adverse events constitutes an 

unanticipated adverse device effect 

under 21 CFR 812.46(b) and 

812.150(b)(1). 

In the guidance (section VI.B), FDA 

recommends that sponsors establish a 

charter describing DMC obligations, 

responsibilities, and standard operating 

procedures. The charter should address, 

for example, the following: 


lotter on DSK11XQN23PROD with NOTICES1
10086 Federal Register / Vol. 89, No. 30 / Tuesday, February 13, 2024 / Notices 

1. Procedures for assessing financial 

and intellectual conflicts of interest of 

proposed DMC members, including 

identifying any concurrent service of 

any DMC member on other DMCs for 

trials of the same, related, or competing 

product; 

2. how unblinded analyses will be 

prepared (e.g., by an independent 

statistician) for the DMC and at what 

frequency; and 

3. procedures to maintain the 

confidentiality of interim comparative 

data in communications between the 

DMC, the sponsor, and (if applicable) 

outside parties to ensure that such data 

available to the DMC are not 

inappropriately disclosed or disclosed 

without appropriate protections. 

This draft guidance is being issued 

consistent with FDA’s good guidance 

practices regulation (21 CFR 10.115). 

The draft guidance, when finalized, will 

represent the current thinking of FDA 

on ‘‘Use of Data Monitoring Committees 

in Clinical Trials.’’ It does not establish 

any rights for any person and is not 

binding on FDA or the public. You can 

use an alternative approach if it satisfies 

the requirements of the applicable 

statutes and regulations. 

II. Paperwork Reduction Act of 1995 

Under the Paperwork Reduction Act 

of 1995 (PRA) (44 U.S.C. 3501–3521), 

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 revision 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. 

Use of Data Monitoring Committees in 

Clinical Trials 

OMB Control Number 0910–0581— 

Revision 

This collection of information 

supports recommendations found in the 

Agency guidance. The draft guidance 

document entitled ‘‘Use of Data 

Monitoring Committees in Clinical 

Trials’’ addresses the roles, 

responsibilities, and operating 

procedures of DMCs and 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; and (4) DMC reports 

based on meeting minutes to the 

sponsor. The submission of the 

requested information provides the 

appropriate parties with essential 

information regarding the clinical trial 

upon which they may base their 

recommendations. 

1. Sponsor Reporting to FDA on DMC 

Recommendations Related to Safety 

FDA recommends that sponsors 

inform FDA about all DMC 

recommendations related to the safety of 

the investigational product, whether or 

not the adverse events that led to the 

recommendation meet the definition of 

serious. 

2. Charters and SOPs for DMCs 

In section VI.B of the guidance, we 

outline recommendations for 

establishing a DMC charter describing 

SOPs. The SOPs ensure that established 

written procedures are followed and 

proper recordkeeping is performed. 

In section VII of the guidance, we 

outline the relationships of the DMC 

members and the sponsors to address 

the independence of the DMC from the 

sponsor. 

3. DMC Meeting Records 

FDA recommends that the DMC keep 

minutes of all meetings but use separate 

minutes for open and closed sessions. 

4. 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. This report 

should include sufficient information to 

explain the rationale for any 

recommended changes. Sponsors 

should establish procedures to 

minimize bias, such as requiring that 

reports to the sponsor include only 

those data generally available to the 

sponsor (e.g., number screened, number 

enrolled at each site) (see 21 CFR 

314.126(b)(5) and 860.7(f)(1)). FDA may 

request copies of DMC meeting records 

when the trial is completed (21 CFR 

312.58 and 812.150(b)(10)) and may also 

request access to the electronic data sets 

used for each set of interim analysis. 

FDA therefore recommends that 

sponsors arrange for archiving such 

electronic data sets. 

Description of the Respondents: The 

submission and data collection 

recommendations described in this 

document affect sponsors of clinical 

trials and DMCs. 

FDA estimates the burden of this 

collection of information as follows: 

TABLE 1—ESTIMATED ANNUAL REPORTING BURDEN 1

Section of guidance; 

reporting activity 

Number of 

respondents 

Number of 

responses per 

respondent 

Total annual 

responses 

Average 

burden 

per response 

Total 

hours 

Section VIII; Sponsor reporting to 

FDA on DMC recommendations 

related to safety.

74 1 74 0.5 (30 minutes) ............................... 37 

Total ........................................... ........................ ........................ ........................ ........................................................... 37 

1There are no capital costs or operating and maintenance costs associated with this collection of information. 


lotter on DSK11XQN23PROD with NOTICES1
Federal Register / Vol. 89, No. 30 / Tuesday, February 13, 2024 / Notices 10087 

TABLE 2—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1

Section of guidance; 

recordkeeping activity 

Number of 

recordkeepers 

Number of 

records per 

recordkeeper 

Total annual 

records 

Average 

burden per 

recordkeeping 

Total 

hours 

Sections VI and VII; Charters and 

SOPs for DMCs .................................. 74 1 74 8 592 

Section VI.6.C.4.b.; DMC meeting 

records ............................................... 740 1 740 2 1,480 

Total ................................................ .............................. .............................. .............................. .............................. 2,072 

1There are no capital costs or operating and maintenance costs associated with this collection of information. 

TABLE 3—ESTIMATED ANNUAL THIRD-PARTY DISCLOSURE BURDEN 1

Section of guidance; 

disclosure activity 

Number of 

respondents 

Number of 

disclosures 

per 

respondent 

Total annual 

disclosures 

Average 

burden per 

disclosure 

Total 

hours 

Section VI.C.4.; DMC reports of meeting minutes to the 

sponsor ............................................................................. 740 2 1,480 1 1,480 

1There are no capital costs or operating and maintenance costs associated with this collection of information. 

Reporting, Recordkeeping, and ThirdParty Disclosure Burdens: Based on our 

experience and the anticipated increase 

in DMC use, FDA estimates that there 

are approximately 1,480 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 740 clinical trials. For the 

purposes of this information collection, 

FDA estimates that each sponsor is 

responsible for approximately 10 trials, 

resulting in an estimated 74 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 using 

a DMC, 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. 

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 

(closed and open meeting sessions) to 

the sponsor. One set of both of the 

meeting records should be maintained 

per clinical trial. 

Based on a review of the information 

collection since our last request for 

OMB approval, our estimated burden for 

the information collection reflects an 

overall increase in burden of 1,183 

hours and a corresponding increase of 

1,794 responses. We attribute this 

increase generally to an adjustment in 

respondents based on our experience 

and the anticipated increase in DMC 

use. In table 3, since we removed the 

language in this draft guidance 

regarding waivers, we removed the 

‘‘sponsor notification to the DMC 

regarding waivers’’ task from the burden 

table, resulting in a decrease of 1 

response. In addition, the sections in the 

draft guidance were changed; therefore, 

we updated the section numbers in the 

burden tables in accordance with the 

draft guidance. 

This draft guidance also refers to 

previously approved FDA collections of 

information found in FDA regulations. 

The collections of information in 21 

CFR parts 50 and 56 have been 

approved under OMB control number 

0910–0130. The collections of 

information in 21 CFR part 312 have 

been approved under OMB control 

number 0910–0014. The collections of 

information in 21 CFR part 314 have 

been approved under OMB control 

number 0910–0001. The collections of 

information pertaining to good clinical 

practice have been approved under 

OMB control number 0910–0843. The 

collections of information in 21 CFR 

part 812 have been approved under 

OMB control number 0910–0078. The 

collections of information in 21 CFR 

part 54 pertaining to financial 

disclosure by clinical investigators have 

been approved under OMB control 

number 0910–0396. 

III. Electronic Access 

Persons with access to the internet 

may obtain an electronic version of the 

draft guidance at https://www.fda.gov/ 

drugs/guidance-compliance-regulatoryinformation/guidances-drugs, https:// 

www.fda.gov/vaccines-blood-biologics/ 

guidance-compliance-regulatoryinformation-biologics/biologicsguidances, https://www.fda.gov/ 

medical-devices/device-advicecomprehensive-regulatory-assistance/ 

guidance-documents-medical-devicesand-radiation-emitting-products, 

https://www.fda.gov/regulatoryinformation/search-fda-guidancedocuments, or https:// 

www.regulations.gov. 

Dated: February 6, 2024. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2024–02849 Filed 2–12–24; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Health Resources and Services 

Administration 

Update to the Bright Futures 

Periodicity Schedule as Part of the 

HRSA-Supported Preventive Services 

Guidelines for Infants, Children, and 

Adolescents; Correction 

AGENCY: Health Resources and Services 

Administration (HRSA), Department of 

Health and Human Services (HHS). 

ACTION: Notices; correction. 

SUMMARY: HRSA published documents 

in the Federal Register of October 24, 


lotter on DSK11XQN23PROD with NOTICES1