[Federal Register: August 25, 2003 (Volume 68, Number 164)]
[Notices]               
[Page 51020-51023]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr25au03-45]                         

-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2003N-0360]

 
Agency Information Collection Activities; Proposed Collection; 
Comment Request; Information Program on Clinical Trials for Serious or 
Life-Threatening Diseases: Maintaining a Databank

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 
contained in the final guidance entitled ``Information Program on 
Clinical Trials for Serious or Life-Threatening Diseases: Maintaining a 
Databank,'' dated March 18, 2002.

DATES: Submit written or electronic comments on the collection of 
information by October 24, 2003.

ADDRESSES: Submit electronic comments on the collection of information 
to http://www.accessdata.fda.gov/scripts/oc/dockets/edockethome.cfm. 
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: Karen L. Nelson, Office of Management 
Programs (HFA-250), Food and Drug Administration, 5600 Fishers Lane, 
Rockville, MD 20857, 301-827-1482.

SUPPLEMENTARY INFORMATION:

I. Background

    Under the PRA (44 U.S.C. 3501-3520), Federal agencies must obtain 
approval from the Office of Management

[[Page 51021]]

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: (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.

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

    Description: In the Federal Register of March 18, 2002 (65 FR 
12022), FDA issued a final 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 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 final guidance 
describes three collections of information: Mandatory submissions, 
voluntary submissions, and 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: (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.

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 
No. 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 final 
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.
---------------------------------------------------------------------------

    \1\Estimate obtained from a review of 2,062 protocols submittted 
to CDER between January 1, 2002, and September 30, 2002.
---------------------------------------------------------------------------

    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\2\ 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

[[Page 51022]]

estimated 50 percent\2\ 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.
---------------------------------------------------------------------------

    \2\Estimate obtained from a review of 2,062 protocols submitted 
to CDER between January 1, 2002, and September 30, 2002.
---------------------------------------------------------------------------

    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.
    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 (65 FR 16620), the agency 
requested comments on the proposed collection of information. One 
comment was received. The comment 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. Our final burden estimate incorporated 
these concerns and included a revised burden estimate.
    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 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 IND's, consideration of the above 
information, 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 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.
    FDA estimates the burden of this collection of information as 
follows:

                                 Table 1.--Estimated Annual Reporting Burden\1\
----------------------------------------------------------------------------------------------------------------
               Recruitment    Protocol         New                         Total       Hours per
New Protocols    Complete     Changes     Investigators  Site Closed     Responses      Reponse     Total Hours
----------------------------------------------------------------------------------------------------------------
CDER                 1,306        1,568           3,108        3,108          10,396      4.6             47,822
 (mandatory);
 1,306
----------------------------------------------------------------------------------------------------------------
CBER                   300          543             585          585           2,313      4.6             10,640
 (mandatory);
 300
----------------------------------------------------------------------------------------------------------------
CDER                 2,651        3,182           6,311        6,311          21,106      4.6             97,088
 (voluntary);
 2,651
----------------------------------------------------------------------------------------------------------------
CBER                   610        1,103           1,188        1,188           4,699      4.6             21,615
 (voluntary);
 610
----------------------------------------------------------------------------------------------------------------
Total                                                                                                    177,165
----------------------------------------------------------------------------------------------------------------
\1\There are no capital and startup costs, or operation and maintenance costs associated with this collection of
  information.


[[Page 51023]]

    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: August 18, 2003.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 03-21624 Filed 8-22-03; 8:45 am]

BILLING CODE 4160-01-S