[Federal Register Volume 65, Number 61 (Wednesday, March 29, 2000)]
[Notices]
[Pages 16620-16623]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-7654]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 00D-1033]


Draft Guidance for Industry on Information Program on Clinical 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

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a draft guidance for industry entitled ``Information 
Program on Clinical Trials for Serious or Life-Threatening Diseases: 
Establishment of a Data Bank.'' The draft guidance provides 
recommendations for sponsors of investigational new drug applications 
(IND's) 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 (NLM) at the National Institutes of 
Health (NIH). Section 113 of the Food and Drug Administration 
Modernization Act (Modernization Act) required the establishment of 
this data bank and specified what information was to be submitted for 
it.

DATES: Submit written comments on the draft guidance by May 30, 2000. 
The deadline for submission of comments on the information collection 
requirements is May 30, 2000. General comments on agency guidance 
documents are welcome at any time.

ADDRESSES: Copies of this draft guidance for industry are available on 
the Internet at http://www.fda.gov/cder/guidance/index.htm or http://www.fda.gov/cber/guidelines.htm. Submit written requests for single 
copies of the draft guidance to the Drug Information Branch (HFD-210), 
Center for Drug Evaluation and Research (CDER), Food and Drug 
Administration, 5600 Fishers Lane, Rockville, MD 20857, or to the 
Office of Communication, Training, and Manufacturers Assistance (HFM-
40), Center for Biologics Evaluation and Research (CBER), 1401 
Rockville Pike, Rockville, MD 20852-1448, 301-827-3844, FAX 888-
CBERFAX. Send one self-addressed adhesive label to assist that office 
in processing your requests. Submit written comments on the draft 
guidance or on the collection of information requirements to the 
Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, rm. 1061, Rockville, MD 20852. Requests and comments 
should be identified with the docket number found in brackets in the 
heading of this document.

FOR FURTHER INFORMATION CONTACT: Theresa A. Toigo (HF-12), Center for 
Drug Evaluation and Research, Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-827-4460.

SUPPLEMENTARY INFORMATION:

I. Description of Guidance

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Information Program on Clinical Trials for Serious or Life-
Threatening Diseases: Establishment of a Data Bank.'' The draft 
guidance is intended to provide recommendations for sponsors of IND's 
on submitting information about clinical trials for serious or life-
threatening diseases to a clinical trials data bank developed by the 
NLM, NIH.
    The Modernization Act (Public Law 105-115), enacted on November 21, 
1997, amends section 402 of the Public Health Service Act (the PHS Act) 
(42 U.S.C. 282) and directs the Secretary of Health and Human Services 
(the Secretary), acting through the Director of NIH, to establish, 
maintain, and operate a data bank of information on clinical trials for 
drugs for serious or life-threatening diseases and conditions 
(hereafter referred to as the Clinical Trials Data Bank).
    The Clinical Trials Data Bank is intended to be a central resource, 
providing current information on clinical trials to individuals with 
serious or life-threatening diseases, to other members of the public, 
and to health care providers and researchers. Specifically, the 
Clinical Trials Data Bank will contain information about both federally 
and privately funded studies of experimental treatments for patients 
with serious or life-threatening diseases conducted under FDA's IND 
regulations (part 312 (21 CFR part 312)). This Clinical Trials Data 
Bank expands upon currently available information on federally-
sponsored trials in various data bases within NIH (e.g., NIH Intramural 
Clinical Center Studies, Physician's Data Query/National Cancer 
Institute) and information about federally and privately sponsored 
human immunodeficiency virus/acquired immune deficiency syndrome HIV/
AIDS trials made available through the AIDS Clinical Trials Information 
Service (ACTIS).
    The NLM is developing the Clinical Trials Data Bank and 
implementing it in a phased approach. The first version of the Clinical 
Trials Data Bank was made available to the public on February 29, 2000. 
The new data base can be reached at http://clinicaltrials.gov. It 
includes primarily NIH-sponsored trials. Later in 2000, data from other 
Federal agencies and the private sector will be incorporated.
    The draft guidance provides recommendations for industry on the 
submission of protocol information to the Clinical Trials Data Bank. It 
includes information on the types of clinical trials for which 
submissions will be required under section 113 of the Modernization 
Act, as well as the types of information to be submitted. An 
implementation plan, addressing procedural issues, will be available 
later in 2000. The implementation plan will include information on how 
to submit protocols to the Clinical Trials Data Bank, and how to 
provide certification to the Secretary that disclosure of information 
for a particular protocol would substantially interfere with the timely 
enrollment of subjects in the clinical investigation. It will also 
discuss issues related to the voluntary submission of information not 
required by section 113 of the Modernization Act (e.g., study results, 
trials for non-serious or non-life-threatening diseases). Until the 
implementation guidance document is available, sponsors submitting 
clinical trials information for inclusion in the ACTIS data bank should 
continue to follow procedures currently in place. Non-NIH sponsors of 
clinical trials for other serious or life-threatening diseases need not 
provide clinical trials information to the data bank until after 
procedures are described in the implementation plan that will be 
available later this year. When the procedures are issued, we will 
establish a timeframe for submitting the information.
    In developing a plan for making publicly available information from 
the Clinical Trials Data Bank, FDA and NIH considered comments 
submitted to Docket No. 98D-0293, ``Section 113 NIH Data Bank--Clinical 
Trials for Serious Diseases.'' A phased approach was used for 
developing guidance. This first document addresses general information 
on the scope of the data bank. The second guidance will be on 
implementation and will be developed

[[Page 16621]]

based on the initial data bank experience using NIH-sponsored trials.
    In addition to NLM's development of the Clinical Trials Data Bank, 
NIH will be evaluating options for making available clinical trials 
information through a toll-free telephone system. Further, section 
113(b) of the Modernization Act directed the Secretary to submit a 
report to Congress to determine the public health need, if any, for 
inclusion of device investigations in the data bank, and the adverse 
impact, if any, on device innovation and research in the United States 
if such information is required to be publicly disclosed. A report 
entitled ``A Device Clinical Trials Data Bank--Public Health Need and 
Impact on Industry'' was sent to Congress in November 1999. The report 
is available on the Modernization Act guidance page at http://www.fda.gov/cdrh/modact/modguid.html.
    Section 113(a) of the Modernization Act requires that sponsors of 
IND's submit to the Clinical Trials Data Bank a description of the 
purpose of each experimental drug, eligibility criteria for 
participation in the trial, the location of clinical trial sites, and a 
point of contact for those wanting to enroll in the trial. The statute 
requires that the information be provided in a form that can be readily 
understood by members of the public. This draft guidance provides 
information on how IND sponsors can fulfil the requirements of section 
113(a) of the Modernization Act by submitting information in the 
following four areas: (1) Descriptive information, (2) recruitment 
information, (3) location and contact information, and (4) 
administrative information. FDA and NIH developed these data elements 
based on the legislative requirements and comments submitted to Docket 
No. 98D-0293.
    This draft guidance is being issued consistent with FDA's good 
guidance practices (62 FR 8961, February 27, 1997). The draft guidance 
represents the agency's current thinking on submitting information on 
clinical trials for serious or life-threatening diseases to a Clinical 
Trials Data Bank developed by the NLM. It does not create or confer any 
rights for or on any person and does not operate to bind FDA or the 
public. An alternative approach may be used if such approach satisfies 
the requirements of the applicable statutes, regulations, or both.
    Interested persons may submit to the Dockets Management Branch 
(address above) written comments on the draft guidance. Two copies of 
any comments are to be submitted, except that individuals may submit 
one copy. Comments are to be identified with the docket number found in 
brackets in the heading of this document. The draft guidance and 
received comments are available for public examination in the Dockets 
Management Branch between 9 a.m and 4 p.m., Monday through Friday.

II. The Paperwork Reduction Act of 1995

    Under the Paperwork Reduction Act of 1995 (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 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 before submitting the collection to OMB for 
approval. To comply with this requirement, FDA is publishing notice of 
the proposed collection of information listed below in this document.
    With respect to the following collection of information, FDA 
invites comment on: (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 on respondents, including through the use of automated 
collection techniques, when appropriate, and other forms of information 
technology.
    Title: Draft Guidance for Industry on Information Program on 
Clinical Trials for Serious or Life-Threatening Diseases: Establishment 
of a Data Bank.
    Description: FDA is issuing a draft guidance to industry on 
recommendations for IND sponsors on submitting information about 
clinical trials for serious or life-threatening diseases to a Clinical 
Trials Data Bank developed by the NLM, NIH. The draft guidance 
describes procedures for IND sponsors to submit information about 
clinical trials of experimental treatments for serious or life-
threatening diseases. 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.

A. Mandatory Submissions

    Section 113 of the Modernization Act 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.

B. 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.

C. 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 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

[[Page 16622]]

regulated by the agency under the Federal Food, Drug, and Cosmetic Act 
or section 351 of the PHS Act 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 part 312, and 
this collection of information is approved by OMB under 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 .
    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.
    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 sixty-five 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. 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 is anticipated that original protocol submissions to the data 
bank will be updated 2.5 times each (mean value, based on an average of 
1.5 updates for protocol changes or addition of investigational sites, 
plus one update regarding completion of recruitment for the protocol), 
for a total of 13,765 responses (5,965 mandatory responses and 7,801 
voluntary responses) per year under section 113 of the Modernization 
Act.
    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 estimates 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. 
Expenditure of 5.6 hours per submission, for 13,765 submissions, 
results in a total of 77,084 hours spent per year by respondents in 
response to section 113(a) of the Modernization Act (33,404 hours for 
mandatory responses and 43,680 hours for voluntary responses).
    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. Table 1 of this document reflects the estimate of this 
total burden.
    FDA estimates the burden of this collection of information as 
follows:

[[Page 16623]]



                                                      Table 1.--Estimated Annual Reporting Burden 1
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                                                                                             Number of
               Submissions                Number of CDER  Number of CBER   Total Number    Responses per   Total Annual      Hours per      Total Hours
                                            Respondents     Respondents   of Respondents    Respondent       Responses       Response
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Total mandatory submissions                 2,235             151           2,386               2.5         5,965               5.6        33,404
Total voluntary submissions                 2,923             197           3,120               2.5         7,800               5.6        43,680
Total                                       5,158             348           5,506               2.5        13,765               5.6       77,084
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\1\There are no capital costs associated with this collection of information.


    Dated: March 20, 2000.
Margaret M. Dotzel,
Acting Associate Commissioner for Policy.
[FR Doc. 00-7654 Filed 3-28-00; 8:45 am]
BILLING CODE 4160-01-F