[Federal Register Volume 72, Number 202 (Friday, October 19, 2007)]
[Notices]
[Pages 59295-59297]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-20662]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2007N-0182]


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 a Data Bank

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 
November 19, 2007.

ADDRESSES:  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: FDA Desk Officer, 
FAX: 202-395-6974, or e-mailed to [email protected]. All comments 
should be identified with the OMB control number 0910-0459. Also 
include the FDA 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: 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 Data Bank--(OMB Control Number 0910-0459)--
Extension

    In the Federal Register of March 18, 2002 (67 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 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)

[[Page 59296]]

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 
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.

[[Page 59297]]

    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 
pulldown 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.
    In the Federal Register of May 14, 2007 (72 FR 27140), FDA 
published a 60-day notice requesting public comment on the information 
collection provisions. No comments were received.
    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   Sites Closed     Responses    Response   Total  Hours
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CDER (mandatory)                                 1,620        1,620          2,507           3,725        13,197         4.6        60,706
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CBER (mandatory)                                   158          158            282             176           950         4.6         4,370
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CDER (voluntary)                                 3,238        3,238          5,090           7,562        26,690         4.6       122,774
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CDER (voluntary)                                   316          316            573             356         1,917         4.6         8,818
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Total                                                                                                                              196,668
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\1\There are no capital costs or operating 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 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: October 15, 2007.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E7-20662 Filed 10-18-07; 8:45 am]
BILLING CODE 4160-01-S