[Federal Register Volume 69, Number 33 (Thursday, February 19, 2004)]
[Notices]
[Pages 7753-7755]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-3488]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2003N-0360]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Information Program 
on Clinical Trials for Serious or Life-threatening Diseases: 
Maintaining of a Databank

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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

DATES: Fax written comments on the collection of information by March 
22, 2004.

ADDRESSES: OMB is still experiencing significant delays in the regular 
mail, including first class and express mail, and messenger deliveries 
are not being accepted. To ensure that comments on the information 
collection are received, OMB recommends that written comments be faxed 
to the Office of Information and Regulatory Affairs, OMB, Attn: Fumie 
Yokota, Desk Officer for FDA, FAX: 202-395-6974.

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

SUPPLEMENTARY INFORMATION: 

I. Background

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

Information Program on Clinical Trials for Serious or Life-threatening 
Diseases: Maintaining a Databank --(OMB Control Number 0910-0459)--
Extension

    In the Federal Register of March 18, 2002 (65 FR 12022), FDA issued 
a guidance to industry on recommendations for investigational new drug 
application (IND) sponsors on submitting information about clinical 
trials for serious or life-threatening diseases to the 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 guidance describes the following three collections of 
information: (1) Mandatory submissions, (2) voluntary submissions, and 
(3) certifications.

II. Mandatory Submissions

    Section 113 of the Food and Drug Administration Modernization Act 
of 1997 (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 final guidance discusses how sponsors can fulfill 
the requirements of section 113 of the Modernization Act. Specifically, 
sponsors should provide the following: (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. Senate 1789, ``Best Pharmaceuticals for 
Children Act'' (BPCA) (Public Law 107-109) established a new 
requirement for the Clinical Trials Data Bank mandated by section 113 
of the Modernization Act. Information submitted to the data bank must 
now include ``* * * a description of whether, and through what 
procedure, the manufacturer or sponsor of the investigation of a new 
drug will respond to requests for protocol exception, with appropriate 
safeguards, for single-patient and expanded protocol use of the new 
drug, particularly in children.'' The final guidance will be updated to 
include a discussion of how sponsors can fulfill the BPCA requirements.

III. 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.

[[Page 7754]]

IV. 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 January 31, 2006, 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. Procedures (where and how) for the actual submission of this 
information to the Clinical Trials Data Bank are addressed in the 
guidance. The Center for Drug Evaluation and Research (CDER) received 
3,957 new protocols in 2002. 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\1\ 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 3,957 protocols per year is 2,638 new protocols per 
year. An estimated 50 percent\1\ 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. Fifty percent of 2,638 protocols per year is 1,319 new protocols 
per year subject to mandatory reporting. The remaining 2,638 new 
protocols per year are subject to voluntary reporting.
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    \1\ Estimate obtained from a review of 2,062 protocols submitted 
to CDER between January 1, 2002, and September 20, 2002.
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    The Center for Biologics Evaluation and Research (CBER) received 
910 new protocols in 2002. 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 
910 new protocols per year is 607 new protocols per year. An estimated 
50 percent\1\ of the new protocols for serious or life-threatening 
diseases submitted to CBER are for clinical trials involving 
assessments for effectiveness. Fifty percent of 607 protocols per year 
is an estimated 304 new protocols per year subject to the mandatory 
reporting requirements under section 113 of the Modernization Act. The 
remaining 606 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 1,319 for CDER plus 304 
for CBER, or 1,623 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 (4,867) minus the protocols subject to mandatory reporting 
requirements (1,623) will be subject to voluntary reporting, or 3,244 
protocols. Our total burden estimate includes multi-center studies and 
accounts for the quality control review of the data before it is 
submitted to the data bank. The number of IND amendments submitted in 
2002 for protocol changes (e.g., changes in eligibility criteria) was 
4,750 for CDER and 1,646 for CBER. The number of IND amendments 
submitted in 2002 for new investigators was 9,419 for CDER and 1,773 
for CBER. The number of protocol changes and new investigators was 
apportioned proportionally between mandatory and voluntary submissions. 
We (FDA) 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 
(9,419 CDER and 1,773 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 (3,957 CDER and 910 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 INDs, consideration of the information previously presented, 
and further consultation with sponsors who submit protocol information 
to the Clinical Trials Data Bank, FDA estimated that approximately 4.6 
hours on average would be needed per response. The estimate 
incorporates 2.6 hours for data extraction and 2.0 hours for 
reformatting based on data collected from organizations currently 
submitting protocols to the Clinical Trials Data Bank. We considered 
quality control issues when developing the current burden estimates of 
2.6 hours for data extraction and the 2.0 hours estimated for 
reformatting. Additionally, the internet-based data entry system 
developed by NIH incorporates features that further decrease the 
sponsor's time requirements for quality control procedures. The 
Clinical Trials Data Bank was set up to receive protocol information 
transmitted electronically by sponsors. Approximately 10 percent of 
sponsors electronically transmit information to the Clinical Trials 
Data Bank. If the sponsor chooses to manually enter the protocol 
information, the data entry system allows it to be entered in a uniform 
and efficient manner primarily through pull-down menus. As sponsor's 
familiarity with the data entry system increases, the hourly burden 
will continue to decrease. 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

[[Page 7755]]

requirements of section 113 of the Modernization Act that will be 
subject to a certification submission. To date, no certifications have 
been received. 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 reflects the 
estimate of this total burden.
    In the Federal Register of August 25, 2003 (68 FR 51020), FDA 
published a 60-day notice requesting public comment on the information 
collection provisions. No comments were received. Some of the estimates 
in table 1 of this document have been changed due to a miscalculation 
in the 60-day notice. The total burden, however, remains unchanged.

                                                     Table 1.--Estimated Annual Reporting Burden\1\
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                                              Recruitment      Protocol           New                            Total        Hours per
               New Protocols                   Complete         Changes      Investigators    Site Closed      Responses      Response      Total Hours
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CDER (mandatory); 1,319                              1,319           1,568           3,108           3,108          10,422       4.6              47,941
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CBER (mandatory); 304                                  304             543             585             585           2,321       4.6              10,677
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CDER (voluntary); 2,638                              2,638           3,182           6,311           6,311          21,080       4.6              96,968
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CBER (voluntary); 606                                  606           1,103           1,188           1,188           4,691       4.6              21,579
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Total                                                4,867  ..............  ..............  ..............          38,514  ............         177,165
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

    We believe the estimate, 177,165 hours per year (38,514 responses x 
4.6 hours per response) accurately reflects the burden. We recognize 
that companies who are less familiar with the data entry system and the 
Clinical Trials Data Bank will require greater than 4.6 hours per 
response. However, as sponsor familiarity with the system increases, 
the hourly estimate will decrease.

    Dated: February 10, 2004.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 04-3488 Filed 2-18-04; 8:45 am]
BILLING CODE 4160-01-S