58970 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Notices 

ANNUAL BURDEN ESTIMATES

Instrument Number of 

respondents 

Number of 

responses per 

respondent 

Average burden 

hours per 

response 

Total burden 

hours 

45 CFR Part 1301 ........................................................................... 2,500 2 2 10,000 

Estimated Total Annual Burden 

Hours: 10,000. 

In compliance with the requirements 

of Section 506(c)(2)(A) of the Paperwork 

Reduction Act of 1995, the 

Administration for Children and 

Families is soliciting public comment 

on the specific aspects of the 

information collection described above. 

Copies of the proposed collection of 

information can be obtained and 

comments may be forwarded by writing 

to the Administration for Children and 

Families, Office of Administration, 

Office of Information Services, 370 

L’Enfant Promenade, SW., Washington, 

DC 20447, Attn: ACF Reports Clearance 

Officer. E-mail address: 

infocollection@acf.hhs.gov. All requests 

should be identified by the title of the 

information collection. 

The Department specifically requests 

comments on: (a) Whether the proposed 

collection of information is necessary 

for the proper performance of the 

functions of the agency, including 

whether the information shall have 

practical utility; (b) the accuracy of the 

agency’s estimate of the burden of the 

proposed collection of information; (c) 

the quality, utility, and clarity of the 

information to be collected; and (d) 

ways to minimize the burden of the 

collection of information on 

respondents, including through the use 

of automated collection techniques or 

other forms of information technology. 

Consideration will be given to 

comments and suggestions submitted 

within 60 days of this publication. 

Dated: October 3, 2008. 

Janean Chambers, 

Reports Clearance Officer. 

[FR Doc. E8–23798 Filed 10–7–08; 8:45 am] 

BILLING CODE 4184–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2008–N–0521] 

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. 

DATES: Submit written or electronic 

comments on the collection of 

information by December 8, 2008. 

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: 

Jonna Capezzuto, Office of Information 

Management (HFA–710), Food and Drug 

Administration, 5600 Fishers Lane, 

Rockville, MD 20857, 301–796–3794. 

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 an 


jlentini on PROD1PC65 with NOTICES
Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Notices 58971 

ongoing clinical trial. The DMC advises 

the sponsor regarding the continuing 

safety of current participants and those 

yet to be recruited, as well as the 

continuing validity and scientific merit 

of the trial. 

FDA’s guidance document is intended 

to assist sponsors of clinical trials in 

determining when a DMC is needed for 

monitoring a study, and how such 

committees should operate. The 

guidance addresses the roles, 

responsibilities, and operating 

procedures of DMCs, describes certain 

reporting and recordkeeping 

responsibilities, including the 

following: (1) Sponsor notification to 

the DMC regarding waivers, (2) DMC 

reports of meeting minutes to the 

sponsor, (3) sponsor reports to the FDA 

on DMC recommendations related to 

safety, (4) standard operating 

procedures (SOPs) for DMCs, and (5) 

DMC meeting records. 

1. Sponsor Notification to the DMC 

Regarding Waivers 

The sponsor must report to FDA 

serious unexpected adverse events in 

drugs and biologics trials (§ 312.32 (21 

CFR 312.32)) and unanticipated adverse 

events in the case of device trials under 

(§ 812.150(b)(1) (21 CFR 812.150(b)(1))). 

The agency recommends in the 

guidance that sponsors notify DMCs 

about any waivers granted by FDA for 

expedited reporting of certain serious 

events. 

2. DMC Reports of Meeting Minutes to 

the Sponsor 

The agency recommends in the 

guidance that the DMC issue a written 

report to the sponsor based on the DMC 

meeting minutes. Reports to the sponsor 

should include only those data 

generally available to the sponsor. The 

sponsor may convey the relevant 

information in this report to other 

interested parties, such as study 

investigators. Meeting minutes or other 

information that include discussion of 

confidential data would not be provided 

to the sponsor. 

3. Sponsor Reporting to FDA on DMC 

Recommendations Related to Safety 

The requirement of the sponsor to 

report DMC recommendations related to 

serious adverse events in an expedited 

manner in clinical trials of new drugs 

(§ 312.32(c)) would not apply when the 

DMC recommendation is related to an 

excess of events not classifiable as 

serious. Nevertheless, the agency 

recommends in the guidance that 

sponsors inform FDA about all 

recommendations related to the safety of 

the investigational product whether or 

not the adverse event in question meets 

the definition of ‘‘serious.’’ 

4. Standard Operating Procedures for 

DMCs 

In the guidance, we recommend that 

sponsors establish procedures to do the 

following things: 

• Assess potential conflicts of interest 

of proposed DMC members; 

• Ensure that those with serious 

conflicts of interest are not included in 

the DMC; 

• Provide disclosure to all DMC 

members of any potential conflicts that 

are not thought to impede objectivity 

and, thus, would not preclude service 

on the DMC; 

• Identify and disclose any concurrent 

service of any DMC member on other 

DMCs of the same, related or competing 

products; 

• Ensure separation, and designate a 

different statistician to advise on the 

management of the trial, if the primary 

study statistician takes on the 

responsibility for interim analysis and 

reporting to the DMC; and 

• Minimize the risks of bias that arise 

when the primary study statistician 

takes on the responsibility for interim 

analysis and reporting to the DMC, if it 

appears infeasible or highly impractical 

for any other statistician to take over 

responsibilities related to trial 

management. 

5. DMC Meeting Records 

The agency recommends in the 

guidance that the DMC or the group 

preparing the interim reports to the 

DMC maintain all meeting records. This 

information should be submitted to FDA 

with the clinical study report 

(§ 314.50(d)(5)(ii) (21 CFR 

314.50(d)(5)(ii))). 

Description of Respondents: The 

submission and data collection 

recommendations described in this 

document affect sponsors of clinical 

trials and DMCs. 

Burden Estimate: Table 1 of this 

document provides the burden estimate 

of the annual reporting burden for the 

information to be submitted in 

accordance with the guidance. Table 2 

of this document provides the burden 

estimate of the annual recordkeeping 

burden for the information to be 

maintained in accordance with the 

guidance. 

Reporting and Recordkeeping Burdens 

Based on information from FDA 

review divisions, FDA estimates there 

are approximately 740 clinical trials 

with DMCs regulated by the Center for 

Biologics Evaluation and Research, the 

Center for Drug Evaluation and 

Research, and the Center for Devices 

and Radiological Health. FDA estimates 

that the average length of a clinical trial 

is 2 years, resulting in an annual 

estimate of 370 clinical trials. Because 

FDA has no information on which to 

project a change in the use of DMCs, 

FDA estimates that the number of 

clinical trials with DMCs will not 

change significantly in the next few 

years. For purposes of this information 

collection, FDA estimates that each 

sponsor is responsible for 

approximately 10 trials, resulting in an 

estimated 37 sponsors that are affected 

by the guidance annually. 

Based on information provided to 

FDA by sponsors that have typically 

used DMCs for the kinds of studies for 

which this guidance recommends them, 

FDA estimates that the majority of 

sponsors have already prepared SOPs 

for DMCs, and only a minimum amount 

of time is necessary to revise or update 

them for use for other clinical studies. 

FDA receives very few requests for 

waivers regarding expedited reporting of 

certain serious events; therefore, FDA 

has estimated one respondent per year 

to account for the rare instance a request 

may be made. FDA estimates that the 

DMCs would hold two meetings per 

year per clinical trial resulting in the 

issuance of two DMC reports of meeting 

minutes to the sponsor. One set of both 

of the meeting records should be 

maintained per clinical trial. Based on 

FDA’s experience with clinical trials 

using DMCs, FDA estimates that the 

sponsor on average would issue two 

interim reports per clinical trial to the 

DMC. FDA estimates that the DMCs 

would hold two meetings per year per 

clinical trial resulting in the issuance of 

two DMC reports of meeting minutes to 

the sponsor. One set of both meeting 

records should be maintained per 

clinical trial. 

The ‘‘Hours per Response’’ and 

‘‘Hours per Record’’ are based on FDA’s 

experience with comparable 

recordkeeping and reporting provisions 

applicable to FDA regulated industry. 

The ‘‘Hours per Response’’ include the 

time the respondent would spend 

reviewing, gathering, and preparing the 

information to be submitted to the DMC, 

FDA, or the sponsor. The ‘‘Hours per 

Record’’ include the time to record, 

gather, and maintain the information. 

The information collection provisions 

in the guidance for §§ 312.30 (21 CFR 

312.30), 312.32, 312.38 (21 CFR 312.38), 

312.55 (21 CFR 312.55), and 312.56 

have been approved under OMB Control 

No. 0910–0014; § 314.50 has been 

approved under OMB Control No. 0910– 

0001; and §§ 812.35 (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: 


jlentini on PROD1PC65 with NOTICES
58972 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Notices 

TABLE 1.—ESTIMATED ANNUAL REPORTING BURDEN1

Section of Guidance/Reporting 

Activity 

No. of 

Respondents 

Annual Frequency per 

Response 

Total Annual 

Responses 

Hours Per 

Response Total Hours 

4.4.1.2. Sponsor notification to 

the DMC regarding waivers 1 1 1 .25 .25 

4.4.3.2. DMC reports of meeting 

minutes to the sponsor 370 2 740 1 740 

5. Sponsor reporting to FDA on 

DMC recommendations related 

to safety 37 1 37 .5 18.5 

Total 758.75 

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

TABLE 2.—ESTIMATED ANNUAL RECORDKEEPING BURDEN1

Recordkeeping Activity No. of 

Recordkeepers 

Annual Frequency 

per Recordkeeping 

Total Annual 

Records 

Hours Per 

Record Total Hours 

4.1. and 6.4 SOPs for DMCs 37 1 37 8 296 

4.4.3.2. DMC meeting records 370 1 370 2 740 

Total 1,036 

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

Please note that on January 15, 2008, 

the FDA Division of Dockets 

Management Web site transitioned to 

the Federal Dockets Management 

System (FDMS). FDMS is a 

Government-wide, electronic docket 

management system. Electronic 

comments or submissions will be 

accepted by FDA only through FDMS at 

http://www.regulations.gov. 

Dated: September 29, 2008. 

Jeffrey Shuren, 

Associate Commissioner for Policy and 

Planning. 

[FR Doc. E8–23833 Filed 10–7–08; 8:45 am] 

BILLING CODE 4160–01–S 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

Proposed Collection; Comment 

Request; Information Program on 

Clinical Trials: Maintaining a Registry 

and Results Databank 

SUMMARY: In compliance with the 

requirement of Section 3506(c)(2)(A) of 

the Paperwork Reduction Act of 1995 to 

provide opportunity for public comment 

on proposed data collection projects, the 

National Library of Medicine (NLM), the 

National Institutes of Health (NIH) will 

publish periodic summaries of proposed 

projects to be submitted to the Office of 

Management and Budget (OMB) for 

review and approval. 

Proposed Collection: Title: 

Information Program on Clinical Trials: 

Maintaining a Registry and Results 

Databank; Type of Information 

Collection Request: Revision of 

currently approved collection [OMB No. 

0925–0586, expiration date 01/31/2009], 

Form Number: NA; Need and Use of 

Information Collection: The National 

Institutes of Health is modifying the 

clinical trial registry databank 

established under previous law 

[FDAMA, Section 113] to comply with 

provisions of Title VIII of Public Law 

110–85 (Food and Drug Administration 

Amendments Act of 2007). The 

databank collects specified registration 

and results information on certain 

clinical trials identified in the law, with 

the objective of enhancing patient 

enrollment and providing a mechanism 

for tracking subsequent progress of 

clinical trials, to the benefit of public 

health. The databank is widely used by 

patients, physicians, and medical 

researchers; in particular those involved 

in clinical research studies. Public Law 

110–85 expands the scope of clinical 

trials that must be registered in 

ClinicalTrials.gov, increases the clinical 

trial information that must be submitted 

as part of each registration, and requires 

the submission of basic results 

information for registered trials of 

approved drugs, biologics and devices. 

Frequency of Response: Responsible 

parties must submit the required 

registration information not later than 

21 days after enrolling the first subject. 

Results information is to be reported not 

later than 12 months after the 

completion date (as defined in the law), 

but can be delayed under certain 

circumstances. Updates to submitted 

information are required at least once a 

year, unless there are no changes to 

report. Changes in recruitment status 

and completion of a trial must be 

reported not later than 30 days after 

such events. Description of 

Respondents: Respondents are referred 

to in the law as ‘‘responsible parties,’’ 

and are defined as: (1) The sponsor of 

the clinical trial (as defined in 21 CFR 

50.3) or (2) the principal investigator of 

such clinical trial if so designated by a 

sponsor, grantee, contractor, or awardee, 

provided that ‘‘the principal investigator 

is responsible for conducting the trial, 

has access to and control over the data 

from the clinical trial, has the right to 

publish the results of the trial, and has 

the ability to meet all of the 

requirements’’ for submitting 

information under the law. Estimate of 

Burden: The burden associated with this 

information collection consists of two 

parts: the burden associated with 

registration of clinical trials; and the 

burden associated with the reporting of 

results information. In both cases, the 

burden includes the time necessary to 

extract information from the study 

protocol or results record, reformat it, 

enter it into the databank, and provide 

necessary updating over the course of 

the study. It is estimated that 

registration information will be required 


jlentini on PROD1PC65 with NOTICES