[Federal Register Volume 65, Number 218 (Thursday, November 9, 2000)]
[Notices]
[Pages 67385-67388]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-28851]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 00D-1033]


Agency Information Collection Activities; Submission for OMB 
Review; Comment Request; Draft Guidance for Industry on Information 
Program on Clinical Trials for Serious or Life-Threatening Diseases: 
Establishment of a Data Bank

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing that the 
proposed collection of information listed below has been submitted to 
the Office of Management and Budget (OMB) for review and clearance 
under the Paperwork Reduction Act of 1995.

DATES: Submit written comments on the collection of information by 
December 11, 2000.

ADDRESSES: Submit written comments on the collection of information to 
the Office of Information and Regulatory Affairs, OMB, New Executive 
Office Bldg., 725 17th St. NW., rm. 10235, Washington, DC 20503, Attn: 
Wendy Taylor, Desk Officer for FDA.

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

SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has 
submitted the following proposed collection of information to OMB for 
review and clearance.

Draft Guidance for Industry on Information Program on Clinical 
Trials for Serious or Life-Threatening Diseases: Establishment of a 
Data Bank

    In the Federal Register of March 29, 2000 (65 FR 16620), FDA issued 
a draft guidance to industry on

[[Page 67386]]

recommendations for investigational new drug application (IND) sponsors 
on submitting information about clinical trials for serious or life-
threatening diseases to a Clinical Trials Data Bank developed by the 
National Library of Medicine, National Institutes of Health (NIH). This 
information is especially important for patients and their families 
seeking opportunities to participate in clinical trials of new drug 
treatments for serious or life-threatening diseases. The draft guidance 
describes three collections of information: Mandatory submissions, 
voluntary submissions, and certifications.

I. Mandatory Submissions

    Section 113 of the Food and Drug Administration Modernization Act 
(the Modernization Act) (Public Law 105-115) requires that sponsors 
shall submit information to the Clinical Trials Data Bank when the 
clinical trial: (1) Involves a treatment for a serious or life-
threatening disease, and (2) is intended to assess the effectiveness of 
the treatment. The draft guidance discusses how sponsors can fulfill 
the requirements of section 113 of the Modernization Act. Specifically, 
sponsors should provide: (1) Information about clinical trials, both 
federally and privately funded, of experimental treatments (drugs, 
including biological products) for patients with serious or life-
threatening diseases; (2) a description of the purpose of the 
experimental drug; (3) patient eligibility criteria; (4) the location 
of clinical trial sites; and (5) a point of contact for patients 
wanting to enroll in the trial.

II. Voluntary Submissions

    Section 113 of the Modernization Act also specifies that sponsors 
may voluntarily submit information pertaining to results of clinical 
trials, including information on potential toxicities or adverse 
effects associated with the use or administration of the 
investigational treatment. Sponsors may also voluntarily submit studies 
that are not trials to test effectiveness, or not for serious or life-
threatening diseases, to the Clinical Trials Data Bank. This notice of 
proposed collection only applies to the voluntary submission of 
information pertaining to studies that are not trials to test 
effectiveness or not for serious or life-threatening diseases. Any 
paperwork burden associated with the voluntary submission of 
information pertaining to the results of clinical trials will be 
discussed in the implementation document.

III. Certifications

    Section 113 of the Modernization Act specifies that the data bank 
will not include information relating to a trial if the sponsor 
certifies to the Secretary of Health and Human Services (the Secretary) 
that disclosure of the information would substantially interfere with 
the timely enrollment of subjects in the investigation, unless the 
Secretary makes a determination to the contrary.
    Description of Respondents: A sponsor of a drug or biologic product 
regulated by the agency under the Federal Food, Drug, and Cosmetic Act 
or section 351 of the Public Health Service Act (42 U.S.C. 262) who 
submits a clinical trial to test effectiveness of a drug or biologic 
product for a serious or life-threatening disease.
    Burden Estimate: The information required under section 113(a) of 
the Modernization Act is currently submitted to FDA under 21 CFR part 
312, and this collection of information is approved under OMB Control 
Number 0910-0014 until September 30, 2002, and, therefore, does not 
represent a new information collection requirement. Instead, 
preparation of submissions under section 113 of the Modernization Act 
involves extracting and reformatting information already submitted to 
FDA. Although the procedures (where and how) for the actual submission 
of this information have not yet been developed, the agency believes it 
has an adequate basis for the determination of the hourly burden 
related to extracting and reformatting this information. The chart 
below provides an estimate of the annual reporting burden for the 
submission of information to satisfy requirements of section 113 of the 
Modernization Act. The Center for Drug Evaluation and Research (CDER) 
is currently receiving 99.2 new protocols per week (mean value, March 
through May 1999), or 5,158 new protocols per year. CDER anticipates 
that protocol submission rates will remain at or near this level in the 
near future. Of these new protocols, an estimated two-thirds are for 
serious or life-threatening diseases and would be subject to either 
voluntary or mandatory reporting requirements under section 113 of the 
Modernization Act. Two-thirds of 5,158 protocols per year is 3,439 new 
protocols per year. An estimated 65 percent of the new protocols for 
serious or life-threatening diseases submitted to CDER are for clinical 
trials involving assessment for effectiveness, and are subject to the 
mandatory reporting requirements under section 113 of the Modernization 
Act. Sixty-five percent of 3,439 protocols per year is 2,235 new 
protocols per year subject to mandatory reporting. The remaining 2,923 
new protocols per year are subject to voluntary reporting.
    The Center for Biologics Evaluation and Research (CBER) is 
currently receiving 29 new protocols per month, or 348 new protocols 
per year. CBER anticipates that protocol submission rates will remain 
at or near this level in the near future. An estimated two-thirds of 
the new protocols submitted to CBER are for clinical trials involving a 
serious or life-threatening disease, and would be subject to either 
voluntary or mandatory reporting requirements under section 113 of the 
Modernization Act. Two-thirds of 348 new protocols per year is 232 new 
protocols per year. An estimated 65 percent of the new protocols for 
serious or life-threatening diseases submitted to CBER are for clinical 
trials involving assessments for effectiveness. Sixty-five percent of 
232 protocols per year is an estimated 151 new protocols per year 
subject to the mandatory reporting requirements under section 113 of 
the Modernization Act. The remaining 197 new protocols per year are 
subject to voluntary reporting.
    The estimated total number of new protocols for serious or life-
threatening diseases subject to mandatory reporting requirements under 
section 113 of the Modernization Act is 2,235 for CDER plus 151 for 
CBER, or 2,386 new protocols per year. The remainder of protocols 
submitted to CDER or CBER will be subject to voluntary reporting, 
including clinical trials not involving a serious or life-threatening 
disease as well as trials in a serious or life-threatening disease but 
not involving assessment of effectiveness. Therefore, the total number 
of protocols (5,506) minus the protocols subject to mandatory reporting 
requirements (2,386) will be subject to voluntary reporting, or 3,120 
protocols.
    It was originally estimated that the protocol submissions to the 
data bank will be updated 2.5 times per year under section 113 of the 
Modernization Act. In the Federal Register of March 29, 2000, the 
agency requested comments on the proposed collection of information. 
One comment was received. The comments stated that FDA greatly 
underestimated the burden by excluding multicenter studies and not 
accounting for the quality control review of the data before it is 
submitted to the data bank. We estimated that 5,506 new protocols are 
submitted each year and each new protocol is updated 2.5 times per year 
with information that would necessitate

[[Page 67387]]

a change in the data bank. We further estimated that each change 
requires an average of 5.6 hours resulting in 77,084 hours spent by 
respondents per year. These estimates included protocols subject to 
mandatory and voluntary reporting requirements.
    For the revised justification, we reviewed actual IND data from 
1997 to 1999, and as a result of our reanalysis we incorporated new 
estimates that consider multicenter studies. The average number of IND 
amendments submitted annually for protocol changes (e.g., changes in 
eligibility criteria) was 4,019 for CDER and 1,441 for CBER. The 
average number of IND amendments submitted annually for new 
investigators was 7,745 for CDER and 1,349 for CBER. The number of 
protocol changes and new investigators was apportioned proportionally 
between mandatory and voluntary submissions. We recognize that single 
submissions may include information about multiple sites.
    Generally, there is no submission to FDA when an individual study 
site is no longer recruiting study subjects. For this analysis, we 
assumed that the number of study sites closed each year is similar to 
the number of new investigator amendments received by FDA (7,745 CDER 
and 1,349 CBER).
    Generally, there is no submission to FDA when the study is closed 
to enrollment. We estimate the number of protocols closed to enrollment 
each year is similar to the number of new protocols submitted (5,158 
CDER and 348 CBER).
    The hours per response is the estimated number of hours that a 
respondent would spend preparing the information to be submitted under 
section 113(a) of the Modernization Act, including the time it takes to 
extract and reformat the information. FDA has been advised that some 
sponsors lack information system capabilities enabling efficient 
collection of company-wide information on clinical trials subject to 
reporting requirements under section 113(a) of the Modernization Act. 
The estimation of burden under section 113(a) reflects the relative 
inefficiency of this process for these firms.
    Based on its experience reviewing IND's, and consideration of the 
above information, FDA estimated that approximately 5.6 hours on 
average would be needed per response (mean value), based on an 
estimated 3.2 hours for data extraction and 2.4 hours for reformatting. 
We considered quality control issues when developing the original 
burden estimates of 3.2 hours for data extraction and the 2.4 hours 
estimated for reformatting. Additionally, the data entry system being 
developed incorporates features that will further decrease the 
sponsor's time requirements for quality control procedures. No new 
estimates for quality control are included in the reanalysis.
    The new estimate continues to use an average of 5.6 hours per 
response for calculations related to new submissions. Changes related 
to the addition and deletion of investigational sites will involve 
minimal resource commitments from the sponsor. Further, many protocol 
changes will not require changes to the data bank. Other protocol 
changes will require minimal time to make changes to the data bank 
(e.g., modification of eligibility criteria). The 5.6 hours per 
response estimate for these types of responses is high.
    A sponsor of a study subject to the requirements of section 113 of 
the Modernization Act will have the option of submitting data under 
that section or certifying to the Secretary that disclosure of 
information for a specific protocol would substantially interfere with 
the timely enrollment of subjects in the clinical investigation. FDA 
has no means to accurately predict the proportion of protocols subject 
to the requirements of section 113 of the Modernization Act that will 
be subject to a certification submission. However, it is anticipated 
that the burden associated with such certification will be comparable 
to that associated with submission of data regarding a protocol. 
Therefore, the overall burden is anticipated to be the same, regardless 
of whether the sponsor chooses data submission or certification for 
nonsubmission. The table below reflects the estimate of this total 
burden.
    FDA estimates the burden of this collection of information as 
follows:

                                                      Table 1.--Estimated Annual Reporting Burden <SUP>1</SUP>
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                    New      Recruitment    Protocol        New          Sites        Total      Hours per
                                                 Protocols     Complete     Changes    Investigators     Closed     Responses     Response   Total Hours
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CDER (mandatory)..............................        2,235        2,235        1,728         3,330         3,330       12,858          5.6       72,005
CBER (mandatory)..............................          151          151          620           580           580        2,082          5.6       11,659
CDER (voluntary)..............................        2,923        2,923        2,291         4,415         4,415       16,967          5.6       95,015
CBER (voluntary)..............................          197          197          821           769           769        2,753          5.6       15,417
--------------------------------------------------------------------------------------------------------------------------------------------------------
Total.........................................                                                                                                  194,096
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\1\ There are no capital and startup, or operation and maintenance costs associated with this collection of information.

    The revised burden estimate for responses (34,660) is 2.5 times the 
original estimate (13,765).
    We believe that the original burden estimate of 77,084 hours spent 
per year underestimated the burden. The new estimate, 194,096 hours per 
year (34,660 responses x 5.6 hours per response), more accurately 
reflects the burden.
    NIH and FDA are considering a pilot program for the electronic 
submission of protocol information over the Internet. The purpose of 
the pilot project is twofold. First, the pilot project will allow FDA 
to test its systems for receiving electronic submissions under section 
113 of the Modernization Act. Second, the pilot project will provide 
opportunities for volunteers to gain experience in using the prototype 
system that will enable them to provide technical feedback on how well 
the system is working, and also to offer suggestions for change. The 
experience gained from this pilot project also will facilitate the 
development of the implementation plan.
    FDA anticipates that up to 25 sponsors will volunteer to 
participate in a pilot program involving the electronic submission of 
protocol information over the Internet. Protocol information entered 
into the system during the pilot project will be included in the 
Clinical Trials Data Bank (ClinicalTrials.gov). We estimate that each 
sponsor will include 10 protocols in the data bank. We estimate that 
each protocol will be modified two times and add three new sites. It is 
assumed that the sites will remain open for the duration of the pilot. 
The one-time burden estimate for the pilot program is 8,400 (1,500 
responses x 5.6 hours/response). Since

[[Page 67388]]

the pilot protocols will be included in the ClinicalTrials.gov data 
bank, the estimated annual burden for the first year will be reduced by 
the number of protocols included in the pilot.
    FDA estimates the burden of the collection of information as 
follows:

                                  Table 2.--Estimated Annual Reporting Burden <SUP>1</SUP>
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                                     Protocol           New        Total Annual      Hours per
                   New Protocols      Changes      Investigators     Responses       Response       Total Hours
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CDER                  200             400             600           1,200               5.6         6,720
CBER                   50             100             150             300               5.6         1,680
Total                                                                                              8,400
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\1\ There are no capital and startup, or operation and maintenance costs associated with this collection of
  information.


    Dated: November 6, 2000.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 00-28851 Filed 11-8-00; 8:45 am]
BILLING CODE 4160-01-F /