[Federal Register Volume 73, Number 56 (Friday, March 21, 2008)]
[Notices]
[Pages 15163-15165]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-5824]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Submission for OMB Emergency Review; Comment Request; Information 
Program on Clinical Trials for Serious and Life-Threatening Diseases: 
Maintaining a Databank

    Summary: In accordance with Section 3507(j) of the Paperwork 
Reduction Act of 1995, the National Institutes of Health hereby 
publishes notification of an Emergency Clearance for the expansion of 
the information related to the ``Information Program on Clinical Trials 
for Serious and Life-Threatening Diseases: Maintaining a Databank.'' 
The expanded program will include information on certain clinical 
trials of drugs, biologics, and devices, whether or not they relate to 
serious and life-threatening diseases.
    The information collection is essential to the mission of the FDA 
and National Institutes of Health [42 U.S.C. 282(j)(2)(A)(ii)] and is 
critical to meeting their roles in the Clinical Trial Registry that was 
expanded by Public Law 110-85, which was enacted on September 27, 2007.
    NIH cannot reasonably comply with the normal clearance procedures 
for information collection, because the use of normal procedures will 
delay the collection and hinder the agency in accomplishing its mission 
and meeting new statutory requirements, to the detriment of the public 
good. Compelling reason exists for the collection of required 
information for successful planning and implementation of the expansion 
of the Clinical Trial Registry, as described in Public Law 110-85.
    This information collection is essential to the effective 
stewardship of Federal Funds. After consultation with other agencies 
and NIH components, NIH has determined that the information is not 
currently available in any single, reliable, accessible source.
    Proposed Collection: Title: Information Program on Clinical Trials 
for Serious and Life-Threatening Diseases: Maintaining a Databank; Type 
of Information Collection Request: New; Form Number: NA; Need and Use 
of Information Collection: In compliance with provisions of Title VIII 
of Public Law 110-85 (Food and Drug Administration Amendments Act of 
2007) the National Institutes of Health is modifying the clinical trial 
registry established under previous law [ClinicalTrials.gov, 
established in response to FDAMA, Section 113]. The registry collects 
specified information on certain clinical trials identified in the law, 
with the objective of enhancing patient enrollment and providing a 
mechanism for tracking subsequent progress of clinical trials, to the 
benefit of public health. The registry is widely used by patients, 
physicians, and medical researchers, in particular those involved in 
clinical research studies.
    Public Law 110-85 expands the scope of clinical trials that must be 
registered in ClinicalTrials.gov to include certain defined clinical 
trials of drugs, biologics, and devices subject to FDA regulation, 
regardless of whether they are related to serious or life-threatening 
diseases. It also increases the clinical trial information (i.e., 
number of data elements) that must be submitted as part of each 
registration.
    Frequency of Response: Responsible parties for applicable clinical 
trials must submit the required information shortly after the 
initiation of a trial [by the later of 21 days after the first patient 
is enrolled or December 26, 2007]. Updates to registration records are 
thereafter required at least once a year, unless there are no changes 
to report. Changes in recruitment status and completion of a trial must 
be reported not later than 30 days after such events. Records for 
trials that were ongoing (as defined in the Law) as of December 26, 
2007 are also required to be updated to comply with the new 
registration data elements, even if they were previously registered.
    Description of Respondents: Respondents are referred to in the law 
as ``responsible parties.'' The statute defines the responsible party 
as: (1) The sponsor of the clinical trial (as defined in 21 CFR 50.3) 
or (2) the principal

[[Page 15164]]

investigator of such clinical trial if so designated by a sponsor, 
grantee, contractor, or awardee, provided that ``the principal 
investigator is responsible for conducting the trial, has access to and 
control over the data from the clinical trial, has the right to publish 
the results of the trial, and has the ability to meet all of the 
requirements'' for submitting information under the law.
    Estimate of Burden: Under the clearance to date (OMB No. 0910-
0459), the FDA total hours burden was 200,839. The current annual 
reporting burden is shown in Table 1. It is estimated that 
approximately 3,500 applicable clinical trials of drugs and biologics 
and 445 applicable trials of devices will be registered annually in 
accordance with Public Law 110-85, Section 801. This estimate is based 
on FDA reports that in 2005 some 5,332 new clinical trial protocols 
were submitted to its Center for Drug Evaluation and Research and 474 
new protocols were submitted to the Center for Biologics Evaluation and 
Research. FDA projects that rates of submission will remain at or near 
this level in the near future. An estimated 50% of the drug and 
biological protocols received in 2005, or approximately 2,900 
protocols, were for trials involving assessments of effectiveness, 
which would be subject to the provisions of Title VIII of Public Law 
110-85. This figure was raised to 3,500 drug and biological trials per 
year to account for IND-exempt trials that are required to register in 
the expanded registration data bank, but for which a protocol might not 
be sent to FDA. The estimated 445 new applicable device clinical trials 
per year includes trials related to pre-market applications 
(approximately 50 applications to FDA containing 75 clinical trial 
protocols in 2005), 510(k) submissions (approximately 360 submissions 
to FDA containing clinical trial protocols in 2005), and humanitarian 
device exemptions (9 in 2005). The estimates of drug, biologic, and 
device trials computed using this approach are consistent with the 
numbers of relevant trials that were registered with the 
ClinicalTrials.gov registry in calendar year 2007.
    The hour burden accounts for time required to register trials and 
provide necessary updating over the course of the study. Based on 
previous experience, it is estimated that each new registration record 
will be updated an average of 8 times during the course of the study 
(e.g., to reflect protocol changes, additions of investigational sites, 
updates of recruitment status, trial completion). The time to complete 
an initial (new) registration (for trials of drugs, biologics, or 
devices) is estimated to be 7 hours (including time to extract, 
reformat and submit information which has already been produced for 
other purposes), an increase of 50% above the 4.6 hours that was 
estimated by FDA for the smaller set of information collected under 
previous law. The time required for subsequent updates of this 
information is expected to be significantly less than for the original 
registration (as less information must be provided), and is estimated 
at 2 hours per update. Applying these figures to the anticipated 
numbers of trials produces a burden estimate for mandatory, new trial 
registrations of 90,735 hours.

                        Table 1.--Estimated Burden for Mandatory New Trial Registrations
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                                                                                   Average time
          Type of respondents              Number of      Frequency of response    per response     Annual hour
                                          respondents                                 (hours)         burden
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Drugs and Biologics...................           3,500  1 New...................               7          24,500
                                                        8 Subsequent Updates....               2          56,000
Devices...............................             445  1 New...................               7           3,115
                                                        8 Subsequent Updates....               2           7,120
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    Total.............................           3,945  ........................  ..............          90,735
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    In addition to mandatory registrations, the registration databank 
will also receive a large number of voluntary submissions of 
information from registrants who wish to make their information public 
for purposes of recruitment or compliance with other policies (e.g., 
International Committee of Medical Journal Editors). Voluntary 
registration is explicitly authorized in Public Law 110-85 [Pub. L. 
110-85, Section 801(a), adding new 42 U.S.C. 282(j)(4)(A)] and 
information is collected in accordance with the same specifications 
established for mandatory registrations. The number of voluntary 
registrations is estimated by subtracting the anticipated annual number 
of mandatory registrations from the total number of trial registrations 
that is expected. In calendar year 2007, there were approximately 
13,300 new trials registered in the ClinicalTrial.gov registry 
databank, of which some 8,000 were trials with drugs or biologics as an 
intervention, 900 were trials with a device as an intervention, and 
4,400 were other types of trials (e.g., observational studies, 
procedural interventions, behavioral interventions). These figures are 
consistent with the numbers of trials registered during calendar year 
2005. Subtracting the anticipated number of mandatory trial 
registrations (from Table 1) from the anticipated number of total 
registrations (2007 statistics) produces estimated numbers of voluntary 
registrations of 4,500 trials of drugs and biologics, 455 trials of 
devices, and 4,400 trials of other intervention types. To account for a 
possible increase in voluntary submissions resulting from the 
heightened level of attention being devoted to clinical trials 
information, these estimates were raised by 20 percent to 5,400 trials 
of drugs and biologics, 545 trials of devices, and 5,280 trials of 
other intervention types. Assuming the same average time per response 
as for mandatory trials, the annual burden is estimated to be 258,175 
hours (Table 2).

[[Page 15165]]



                               Table 2.--Estimated Burden for Voluntary Reporting
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                                                                                   Average time
          Type of respondents              Number of      Frequency of response    per response     Annual hour
                                          respondents                                 (hours)         burden
----------------------------------------------------------------------------------------------------------------
Drugs and Biologics...................           5,400  1 New...................               7          37,800
                                                        8 Updates...............               2          86,400
Devices...............................             545  1 New...................               7           3,815
                                                        8 Updates...............               2           8,720
Other.................................           5,280  1 New...................               7          36,960
                                                        8 Updates...............               2          84,480
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    Total Voluntary...................          11,225  ........................  ..............         258,175
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    The combined, recurring burden for mandatory and voluntary 
reporting would be the sum of the totals in Tables 1 and 2, or 348,910 
hours. This figure would be expected to decline over time as 
registrants become more familiar with the registration processes and 
refine their data submission systems.
    During the first year of implementation, there will be an 
additional mandatory reporting burden associated with the collection of 
information for applicable trials of drugs, biologics, and devices that 
were ongoing as of December 26, 2007, but had been previously 
registered with ClinicalTrials.gov. These respondents have already 
provided information collected under the previous OMB clearance and 
will provide only the additional elements subject to this clearance. 
The number of trials subject to this requirement is estimated by 
searching the existing ClinicalTrials registry for ongoing, 
interventional Phase 2-4 studies of drugs, biologics, and devices. 
Doing so produces an estimate of 7,650 trials: 7,000 previously 
registered trials of drugs and biologics and 650 previously registered 
trials of devices. It is anticipated that information collection 
required to bring these trials into compliance with the new information 
collection requirements will be significantly less than for a new trial 
registration and is estimated as 3 hours. Information for these trials 
will need to be updated to reflect the continued progress of the trial. 
The number of updates is estimated to be 4, which is half of the 
updates estimated for new registrations. Each update is estimated to 
require 2 hours, consistent with the updates for newly registered 
trials. The total burden associated with the updating of information 
for ongoing trials is 84,150 hours, as shown in Table 3.

               Table 3.--Estimated Burden for Mandatory Updating of Information for Ongoing Trials
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                                                                                   Average time
          Type of respondents              Number of      Frequency of response    per response     Annual hour
                                          respondents                                 (hours)         burden
----------------------------------------------------------------------------------------------------------------
Drugs and Biologics...................           7,000  1 Compliance Update.....               3          21,000
                                                        4 Subsequent Updates....               2          56,000
Devices...............................             650  1 Compliance Update.....               3           1,950
                                                        4 Subsequent Updates....               2           5,200
Total.................................           7,650  ........................  ..............          84,150
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There are no Capital Costs, Operating Costs or Maintenance Costs to report.

    Request for Comments: Written comments and/or suggestions from the 
public and affected agencies should address one or more of the 
following points: (1) Evaluate whether the proposed collection of 
information is necessary for the proper performance of the function of 
the agency, including whether the information will have practical 
utility; (2) Evaluate the accuracy of the agency's estimate of the 
burden of the proposed collection of information, including the 
validity of the methodology and assumptions used; (3) Enhance the 
quality, utility, and clarity of the information to be collected; and 
(4) Minimize the burden of the collection of information on those who 
are to respond, including the use of appropriate automated, electronic, 
mechanical, or other technological collection techniques or other forms 
of information technology.
    Direct Comments to OMB: Written comments and/or suggestions 
regarding the item(s) contained in this notice, especially regarding 
the estimated public burden and associated response time, should be 
directed to the Office of Management and Budget, Office of Regulatory 
Affairs. All comments should be sent via e-mail to [email protected] or by fax to 202-395-6974, Attention: Desk 
Officer for NIH. To request more information on the proposed project or 
to obtain a copy of the data collection plans and instruments, contact: 
David Sharlip, National Library of Medicine, Building 38A, Room B2N12, 
8600 Rockville Pike, Bethesda, MD 20894, or call non-toll free number 
301-402-9680 or E-mail your request to [email protected].
    Comments Due Date: Comments regarding this information collection 
are best assured of having their full effect if received within 15 days 
of the date of this publication.

     Dated: March 14, 2008.
 Betsy L. Humphreys,
Deputy Director, National Library of Medicine, National Institutes of 
Health.
 [FR Doc. E8-5824 Filed 3-20-08; 8:45 am]
BILLING CODE 4140-01-P