FR Doc E7-9221

[Federal Register: May 14, 2007 (Volume 72, Number 92)]
[Notices]
[Page 27140-27142]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr14my07-44]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2007N-0182]

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

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 guidance entitled ``Information Program on Clinical
Trials for Serious or Life-Threatening Diseases and Conditions'' dated
March 18, 2002.

DATES: Submit written or electronic comments on the collection of
information by July 13, 2007.

ADDRESSES: Submit electronic comments on the collection of information
to: http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/dockets/ecomments. 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: Jonna Capezzuto, Office of the Chief
Information Officer (HFA-250), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857, 301-827-4659.

SUPPLEMENTARY INFORMATION: Under 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(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 these topics: (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 Data Bank (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 a Clinical Trials
Data Bank developed by the National Library of Medicine (NLM), 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 three collections of information:
Mandatory submissions, voluntary submissions, and certifications.

Mandatory Submissions

Section 113 of the Food and Drug Administration Modernization Act
(FDAMA) 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 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'' (Public Law
107-109) (BPCA), established a new requirement for the Clinical Trials
Data Bank mandated by section 113 of FDAMA. Information submitted to
the data bank must now include ``a description of

[[Page 27141]]

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 guidance
was updated on January 27, 2004, to include a discussion of how
sponsors can fulfill the BPCA requirements.
As part of the resubmission process for OMB approval, this
information collection request (ICR) has been revised to include the
burden associated with new requirements imposed by the Centers for
Medicare and Medicaid Services (CMS). On September 19, 2000, the Health
Care Financing Administration (now CMS) implemented a Clinical Trial
Policy through the National Coverage Determination process. The
Clinical Trial Policy was developed in response to a June 7, 2000,
executive memorandum, issued by President Clinton, requiring Medicare
to pay for routine patient costs in clinical trials. The original
policy suggested that a registry be established into which studies
meeting the criteria for coverage under the policy would be enrolled
for administrative purposes. This registry was never established.
On July 10, 2006, CMS opened a reconsideration of its national
coverage determination on clinical trials. The purpose of the
reconsideration is to further refine the policy to rename it the
Clinical Research Policy (CRP) to address several ambiguities,
including the link between the CRP and the Coverage with Evidence
Development concept, and the authority to allow the agency to pay for
the costs of limited investigational items. One requirement to qualify
for coverage of clinical costs under the proposed policy is that the
study must be enrolled in the NLM Clinical Trials Data Bank.

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.

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.
For the purposes of CMS, the respondents will be providers that are
conducting or sponsoring clinical trials that are seeking to have the
clinical costs of their studies reimbursed by Medicare.
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 May 31, 2009, 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 4,858
new protocols in 2005. 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 4,858 protocols per year is 3,239 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 3,239 protocols per year is 1,620 new protocols
per year subject to mandatory reporting. The remaining 3,238 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 30, 2002.
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The Center for Biologics Evaluation and Research (CBER) received
474 new protocols in 2005. CBER anticipates that protocol submission
rates will remain at or near this level in the near future. An
estimated two-thirds\1\ 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
474 new protocols per year is 316 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 316 protocols per year
is an estimated 158 new protocols per year subject to the mandatory
reporting requirements under section 113 of the Modernization Act. The
remaining 316 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 1,620 for CDER plus 158 for
CBER, or 1,778 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 (5,332) minus the protocols subject to mandatory reporting
requirements (1,778) will be subject to voluntary reporting, or 3,554
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
2005 for protocol changes (e.g., changes in eligibility criteria) was
7,597 for CDER and 855 for CBER. The number of IND amendments submitted
in 2005 for new investigators was 11,287 for CDER and 532 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

[[Page 27142]]

the number of new investigator amendments received by FDA (11,287 CDER
and 532 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 (4,858
CDER and 474 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 in the previous paragraphs, 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 sponsors' 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 of
this document 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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New Recruitment Protocol New Total Hours per
Protocols Complete Changes Investigators Site Closed Responses Response Total Hours
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CDER 1,620 1,620 2,507 3,725 13,197 4.6 60,706
(mandatory)
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CBER 158 158 282 176 950 4.6 4,370
(mandatory)
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CDER 3,238 3,238 5,090 7,562 26,690 4.6 122,774
(voluntary)
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CDER 316 316 573 356 1,917 4.6 8,818
(voluntary)
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Total 196,668
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\1\There are no capital costs or operation and maintenance costs associated with this collection of information.

CMS Burden Estimate:
The burden associated with CMS' requirements is the time and effort
necessary for the provider to extract the data elements from the study
protocol and reformatting and entering the information into the data
bank. We estimate that approximately 745 clinical research studies will
register on the NLM data bank. The number was derived from a search of
the database on September 1, 2006 restricting the search by age (e.g.,
> 65 years of age); sponsor (e.g., NIH, industry, other federal agency,
university/organization); Phase II, III or IV; and by type of study
(e.g., cancers and other neoplasms, diagnosis, and devices). The age,
sponsor, and study phase was applied to each of the three separate
searches by type of study. The following number of studies by study
type, including trials no longer recruiting was 562 for diagnosis, 164
for cancers and other neoplasms, and 19 for devices. In determining the
total number of hours requested, the CMS estimate uses the same
assumptions used by the FDA to estimate its total number of burden
hours. Therefore, the total annual burden associated with this
requirement is 27,480 hours (5,974 responses x 4.6 hours per response).
We believe the combined estimate of burden attributable to FDA and
CMS requirements, 224,148 burden hours (196,668 burden hours + 27,480
burden hours) accurately reflects the total burden associated with this
information collection request. 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: May 8, 2007.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E7-9221 Filed 5-11-07; 8:45 am]

BILLING CODE 4160-01-S