[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
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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.
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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