[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]
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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.
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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
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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.
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\1\Estimate obtained from a review of 2,062 protocols submittted
to CDER between January 1, 2002, and September 30, 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\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
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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.
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\2\Estimate obtained from a review of 2,062 protocols submitted
to CDER between January 1, 2002, and September 30, 2002.
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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\
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Recruitment Protocol New Total Hours per
New Protocols Complete Changes Investigators Site Closed Responses Reponse Total Hours
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CDER 1,306 1,568 3,108 3,108 10,396 4.6 47,822
(mandatory);
1,306
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CBER 300 543 585 585 2,313 4.6 10,640
(mandatory);
300
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CDER 2,651 3,182 6,311 6,311 21,106 4.6 97,088
(voluntary);
2,651
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CBER 610 1,103 1,188 1,188 4,699 4.6 21,615
(voluntary);
610
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Total 177,165
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\1\There are no capital and startup costs, or operation and maintenance costs associated with this collection of
information.
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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