[Federal Register Volume 74, Number 54 (Monday, March 23, 2009)]
[Notices]
[Pages 12138-12140]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-6198]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health

[Docket No. NIH-2009-0002]


Public Meeting on Expansion of the Clinical Trial Registry and 
Results Data Bank

AGENCY: National Institutes of Health, HHS.

ACTION: Notice of public meeting; request for comments.

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SUMMARY: With this notice, the National Institutes of Health (NIH) of 
the U.S. Department of Health and Human Services (HHS) announces a 
public meeting and requests input from interested parties on issues 
that the agency will consider as it develops regulations to expand the 
clinical trial registry and results data bank commonly known as 
ClinicalTrials.gov in accordance with section 801 of the Food and Drug 
Administration Amendments Act of 2007 (FDAAA) [Pub. L. 110-85]. FDAAA 
requires a public meeting to be held to provide an opportunity for 
input from interested parties with regard to regulations that are to be 
issued within three years of enactment of the law. The NIH seeks input 
from all interested parties about issues to be considered in the 
proposed rulemaking. Comments on these issues will inform the 
development of draft regulations, which will be made available for 
public comment via a separate Notice of Proposed Rulemaking (NPRM) that 
will be issued in the Federal Register at a later date. Section III of 
this document lists specific topics and questions on which input is 
sought.
    Public Meeting Date and Time: The public meeting will be held on 
Monday, April 20, 2009, from 9 a.m. to 5 p.m.
    Location: The public meeting will be held in Masur Auditorium, 
which is located on the NIH Campus, Building 10, South Side, First 
Floor, 10 Center Drive, Bethesda, Maryland 20892. The NIH, like all 
Federal Government facilities, has instituted security measures to 
ensure the safety of its patients, employees, visitors, and facilities. 
All visitors must enter the NIH campus through the Gateway Center, 
which is located adjacent to the Medical Center Metro Station (Red 
Line) at the South Drive entrance to the campus from Rockville Pike/
Wisconsin Avenue (Route 355). Security personnel will ask you to submit 
to vehicle and personal inspection. Visitors over 15 years of age must 
provide a form of government-issued ID, such as a driver's license or 
passport. Visitors under 16 years of age must be accompanied by an 
adult. Additional information is available online at http://www.nih.gov/about/visitor/.
    Registration and participation: The NIH desires broad participation 
in the public meeting. To ensure sufficient seating for all 
participants, we request that you register by 5 p.m. on Monday, April 
13, 2009. Registration may be accomplished online at http://prsinfo.clinicaltrials.gov/public-meeting-april09.html or by submitting 
the following information to the Contact Person indicated below: Name; 
Title; Business affiliation (if any); Address; Telephone and fax 
numbers; and e-mail address. When registering, please indicate whether 
you need any special accommodations (such as wheelchair access). Sign-
language interpretation will be provided at the meeting. Registration 
is on a first-come, first-served basis. Walk-in registrations will be 
accepted at the site on a space-available basis. Interested parties may 
also view the meeting remotely via live videocast, which will be 
accessible on the Internet at http://videocast.nih.gov.

Oral Statements at the Meeting

    Participants wishing to make an oral statement during the public 
meeting should make their request when they register and should submit 
a written statement summarizing their remarks. Written statements 
should be submitted to the meeting docket at http://www.regulations.gov 
or to the Contact Person indicated below by 5 p.m. on Monday, April 13, 
2009. Written statements should identify by number each discussion 
question addressed, and written statements that exceed 10 pages should 
include a one-page executive summary. Registered individuals will be 
notified of the approximate scheduled time of their remarks prior to 
the meeting. The NIH will try to accommodate all persons who wish to 
make a public comment at the meeting, including those who register at 
the site, but it may need to limit the number of presentations and/or 
the time allotted for each presentation. Nevertheless, the full text of 
all written statements will be included in the docket, which will 
remain open for submissions after the conclusion of the meeting. In 
order that they may be considered by the agency during the development 
of the proposed rule, written comments should be submitted to the 
docket by Monday, June 22, 2009. Instructions for submitting written 
comments are described in Section IV of this notice.
    Agenda and other meeting materials: An agenda for the public 
meeting will be posted on the meeting Web site http://prsinfo.clinicaltrials.gov/public-meeting-april09.html and submitted to 
the public docket by Wednesday, April 15, 2009. The NIH may make other 
background material available on the meeting Web site in advance of the 
meeting and will submit all such information to the public docket.
    Contact Person: Christine Ireland, Committee Management Officer, 
National Library of Medicine, 6705 Rockledge Drive, Suite 301, 
Bethesda, MD 20892-7968; telephone: 301-594-4929; fax: 301-402-2952; e-
mail: [email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    The NIH, through its National Library of Medicine (NLM), has 
maintained a clinical trial registry data bank, commonly known as 
ClinicalTrials.gov, since 2000. The registry was established, in part, 
in response to the Food and Drug Administration Modernization Act of 
1997 [Pub.L. 105-115], and as of March 2009 it contained information on 
more than 69,000 clinical trials conducted in more than 160 countries.
    The Food and Drug Administration Amendments Act of 2007 (FDAAA) 
[Pub.L. 110-85], enacted in September of 2007, increases the amount and 
type of clinical trial information that is to be made publicly 
available through the data bank. Section 801 of the FDAAA requires the 
Director of NIH to expand the data bank and requires ``responsible 
parties'' (generally, trial sponsors or designated principal 
investigators) to submit specified registration and results information 
describing ``applicable clinical trials'' (as defined in FDAAA) of 
certain drugs, biological products, and devices. The FDAAA specifies a 
set of registration data elements to be submitted to the data bank and 
authorizes the Secretary to modify the registration data elements by 
regulation if such modification ``improves and does not reduce'' the 
clinical trial information submitted to ClinicalTrials.gov. The FDAAA 
also specifies the deadline by which responsible parties are to submit 
registration information (in general, within 21 days of enrolling the 
first patient) and establishes a requirement

[[Page 12139]]

for updating information if there are changes to report.
    The FDAAA also requires the NIH to expand ClinicalTrials.gov to 
include information describing the results of certain applicable 
clinical trials. The law requires responsible parties to submit ``basic 
results'' information for applicable clinical trials for which the 
drugs, biological products, and devices under study are approved under 
section 505, 515, or 520(m) of the Federal Food, Drug, and Cosmetic 
(FDC) Act, licensed under section 351 of the Public Health Service 
(PHS) Act, or cleared under section 510(k) of the FDC Act. As specified 
in the law, the information to be submitted consists of certain 
administrative information and two categories of numerical data related 
to the clinical trial: (1) A table of demographic and baseline 
characteristics of the patient population, overall and for each arm of 
the clinical trial, including the number of patients who dropped out of 
the clinical trial or were excluded from the analysis; and (2) a table 
of values for each of the primary and secondary outcome measures, for 
each arm of the trial, including the results of scientifically 
appropriate tests of the statistical significance of such outcome 
measures. Narrative summaries of the trial results are not permitted. 
The required basic results information has been implemented in 
ClinicalTrials.gov as four modules of tabular data that describe the 
participant flow, baseline characteristics of the patient population, 
outcome measures and statistical analysis, and adverse events. The 
FDAAA specifies that, in general, results must be submitted not later 
than 12 months after the trial completion date, which is defined as the 
date that the final subject was examined or received an intervention 
for the purposes of final collection of data for the primary outcome; 
however, the law provides several options for delayed submission of 
results information (e.g., when seeking initial approval of a drug or 
device or seeking approval of a new use for the drug or device). The 
FDAAA includes provisions to ensure that information submitted to the 
data bank is complete and accurate and not false, misleading, or 
promotional. The NIH and the Food and Drug Administration (FDA) are 
instructed to conduct a pilot quality control project to determine the 
``optimal method'' of verifying that submitted results information is 
nonpromotional and not false or misleading in any particular way.
    The FDAAA required the NIH Director to modify ClinicalTrials.gov 
to include the required registration information by December 26, 2007, 
and to accommodate the submission of required ``basic results 
information'' by September 27, 2008. The NIH met these deadlines, and, 
since those dates, registration information has been submitted for more 
than 20,000 clinical trials, and basic results information has been 
submitted for more than 430 clinical trials. In addition, data 
providers may submit adverse event reporting information on a voluntary 
basis; reporting of adverse event information will become mandatory at 
a later date.
    To provide more complete results information and to enhance patient 
access to and understanding of the results of clinical trials, the 
FDAAA (as codified in 42 U.S.C. 242(j)(3)(D)) requires the Secretary to 
further expand the registry and results data bank by regulation. The 
regulations are to be promulgated within three years of the law's 
enactment. The FDAAA specifies topics to be considered in developing 
the regulations and requires the Secretary to convene a public meeting 
to solicit input from interested parties with regard to the 
regulations. Specific elements that are to be considered or included in 
the rulemaking are those identified for discussion at the public 
meeting in Section III.

III. Purpose and Scope of the Public Meeting

    This public meeting is intended to provide an opportunity for 
interested parties to share their perspectives on the issues to be 
considered in the rulemaking for the expanded registry and results data 
bank that is required by the FDAAA. The NIH anticipates that the event 
will be of interest to a broad range of stakeholders, including 
patients and human subjects; patient advocacy groups; manufacturers of 
drugs, biological products, and devices whose products are subject to 
registration and results reporting under FDAAA; academic medical 
centers; researchers, and other organizations that engage in clinical 
research; members of Institutional Review Boards; journal editors who 
publish the result of clinical trials; and experts in evidence-based 
medicine who make use of the results of clinical trials. The NIH 
encourages broad participation in the public meeting. To provide an 
additional opportunity for interested parties to provide input on the 
issues to be considered in the rulemaking, the docket will remain open 
for submission of written comments after the meeting. In order for the 
agency to consider the comments during development of the proposed 
rule, the comments should be submitted by Monday, June 22, 2009.

III. Issues for Discussion

    In keeping with the topics to be considered in the rulemaking for 
the expanded registry and results data bank, the NIH invites comments 
from interested parties on any and all of the following topics and 
questions:
    1. Whether to require submission of results information for 
applicable clinical trials of drugs, biological products, and devices 
that are not approved under sections 505, 515, or 520(m) of the FDC 
Act, licensed under section 351 of the PHS Act, or cleared under 
section 510(k) of the FDC Act (whether or not clearance, approval or 
licensure was sought). Please comment on issues such as the potential 
advantages and disadvantages to the public and public health of 
disclosing results information for trials involving drugs, biological 
products, and devices that are not approved, licensed, or cleared; the 
effects (if any) on the development of drugs, biological products, and 
devices; the reporting burden on data submitters; and the appropriate 
timing of submission and public disclosure of information, taking into 
account the certification process established by the FDAAA when 
approval, licensure, or clearance is sought for a product under study 
in an applicable clinical trial. In particular, consider scenarios 
involving trials of different types of unapproved products: (a) 
Applicable clinical trials of products for which marketing applications 
or premarket notification submissions are never submitted to the FDA; 
(b) applicable clinical trials of products for which marketing 
applications or premarket notification submissions are submitted, but a 
decision is pending; and (c) applicable clinical trials of products for 
which marketing applications or premarket notification submissions are 
submitted and the FDA decides not to approve, license, or clear the 
product for marketing.
    2. Whether narrative summaries of the clinical trial and its 
results can be included in the data bank without being misleading or 
promotional. Comment on issues such as the potential advantages and 
disadvantages to patients, research subjects, and the public of 
requiring responsible parties to submit narrative summaries that are 
written in nontechnical, understandable language for patients; the 
utility to the scientific community of requiring responsible parties to 
submit narrative summaries written in technical language; the content 
and structure of any such narratives; and procedures that could be 
established to help ensure the content is not misleading or 
promotional.

[[Page 12140]]

    3. What additional information, if any, that is written in 
nontechnical, understandable language for patients should be required 
to be submitted to the data bank or should be provided in the data bank 
to assist patients in understanding and interpreting the information 
available in the data bank. Please consider the types of information 
that would best assist patients and other members of the public in 
understanding and interpreting results information in the data bank, 
including information on adverse events. Comment on issues such as the 
types of information that might assist patients and the public in 
understanding the results of individual clinical trials and of clinical 
trials in general. Identify existing sources of explanatory information 
that are oriented toward patients and the public and could be included 
in or linked to the data bank.
    4. Whether to require submission of the full clinical trial 
protocol or only such information on the protocol as may be necessary 
to help evaluate the results of the trial. Comment on the value of the 
full clinical trial protocol versus partial information from the 
protocol in evaluating the results of a trial and the completeness of 
results data submission.
    5. Procedures the agency might consider for quality control, with 
respect to completeness and content of clinical trial information, to 
help ensure that data elements are not false or misleading and are 
nonpromotional. Consider the effect of different approaches on the 
workload of both data submitters and the agency and on the quality of 
data available to the public, as well as suitable means for the agency 
to communicate information about its quality assurance processes to 
data submitters and the public.
    6. Whether the 1-year period for submission of basic results 
information should be increased to a period not to exceed 18 months. 
Comment on the advantages and disadvantages of increasing the period 
for submission of clinical trial information from 1-year after the 
completion date to a period not to exceed 18 months. Consider the 
implications for all stakeholders, including governmental bodies, data 
submitters, and users of ClinicalTrials.gov; the extent to which such a 
change would affect public health or the utility of the data bank; the 
possible effect on the number of requests that responsible parties 
would submit to the NIH requesting an extension of the results 
reporting deadline; and the possible improvements to the quality and or 
completeness of initial submissions of results data to the NIH. 
Consider the implications of delay periods of different lengths between 
12 and 18 months.
    7. Whether the clinical trial information required by the 
regulation should be required to be submitted for applicable clinical 
trials for which ``basic results'' information is submitted before the 
effective date of the regulation. Consider the advantages and 
disadvantages to data submitters and users of the data bank, including 
patients, prospective human subjects, care providers, and researchers.
    8. The appropriate timing and requirements for updates of clinical 
trial information and procedures for tracking such updates. Please 
comment on the advantages and disadvantages of requiring more frequent 
updating of information submitted to the clinical trial registry and 
results data bank, which elements (if any) would benefit from more 
frequent updating, and what would be the optimal frequency of such 
updates.
    9. The standard format for the submission of clinical trial 
information required by the regulation, including adverse event 
information, and additions or modifications to the manner of reporting 
of the data elements established under the basic results reporting 
provisions of the FDAAA.
    10. A statement to accompany the entry for an applicable clinical 
trial when the primary and secondary outcome measures for such clinical 
trial are submitted as a ``voluntary submission'' after the date 
specified in the FDAAA for submission of such information.
    11. Other issues associated with Section 801 of the FDAAA that will 
inform rulemaking.

IV. Request for Comments

    As described previously in this Notice, participants wishing to 
make an oral statement at the Public Meeting are requested to notify 
the NIH and to submit to the meeting docket or the Contact Person a 
written version of their remarks on the topics identified in Section IV 
by 5 p.m. on Monday, April 13, 2009. The docket will remain open after 
the meeting, and, regardless of attendance at the public meeting, 
interested persons may submit written or electronic comments to the 
docket so that they may be considered by the agency during the 
subsequent rulemaking. To ensure consideration, written comments should 
be submitted to the docket by Monday, June 22, 2009. Submit electronic 
comments to Docket No. NIH-2009-0002 at http://www.regulations.gov. The 
site contains instructions for submitting comments.

V. Transcripts

    A transcript of the public meeting will be submitted to the docket 
and posted to http://prsinfo.clinicaltrials.gov/public-meeting-april09.html approximately 15 working days after the public meeting.

    Dated: March 16, 2009.
Raynard S. Kington,
Acting Director, National Institutes of Health.
 [FR Doc. E9-6198 Filed 3-20-09; 8:45 am]
BILLING CODE 4140-01-P