80 FR 8096 - Announcement of a Draft NIH Policy on Dissemination of NIH-Funded Clinical Trial Information

DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health

Federal Register Volume 80, Issue 30 (February 13, 2015)

On November 19, 2014, the National Institutes of Health (NIH) published a request for public comments in the NIH Guide for Grants and Contracts on a draft policy to promote broad and responsible dissemination of information on clinical trials funded by the NIH through registration and submission of summary results information to ClinicalTrials.gov. See Guide notice NOT-OD-15-019 at http:// grants.nih.gov/grants/guide/notice-files/NOT-OD-15-019.html. NIH is publishing this notice in order to inform readers of the Federal Register about the draft policy and the opportunity to comment.

[Federal Register Volume 80, Number 30 (Friday, February 13, 2015)]
[Notices]
[Pages 8096-8098]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2015-02994]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Announcement of a Draft NIH Policy on Dissemination of NIH-Funded 
Clinical Trial Information

SUMMARY: On November 19, 2014, the National Institutes of Health (NIH) 
published a request for public comments in the NIH Guide for Grants and 
Contracts on a draft policy to promote broad and responsible 
dissemination of information on clinical trials funded by the NIH 
through registration and submission of summary results information to 
ClinicalTrials.gov. See Guide notice NOT-OD-15-019 at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-019.html. NIH is 
publishing this notice in order to inform readers of the Federal 
Register about the draft policy and the opportunity to comment.

DATES: The deadline for receiving comments on the draft policy is no 
later than 5:00 p.m. on March 23, 2015.

ADDRESSES: Comments may be submitted by any of the following methods:
     Email: [email protected].
     Fax: 301-496-9839.
     Mail/Hand delivery/Courier: Office of Clinical Research 
and Bioethics Policy, Office of Science Policy, National Institutes of 
Health, 6705 Rockledge Drive, Suite 750, Bethesda, MD 20892.

FOR FURTHER INFORMATION CONTACT: Office of Clinical Research and 
Bioethics Policy, Office of Science Policy, National Institutes of 
Health, 6705 Rockledge Drive, Suite 750, Bethesda, MD 20892, 301-496-
9838, [email protected].

SUPPLEMENTARY INFORMATION: 

Background

    The National Institutes of Health (NIH) is dedicated to improving 
the health of Americans by conducting and funding biomedical and 
behavioral

[[Page 8097]]

research, including clinical trials.\1\ A fundamental premise of all 
NIH-funded research is that the results of such work must be 
disseminated in order to contribute to the general body of scientific 
knowledge and, ultimately, to the public health. NIH awardees are 
expected to make the results and accomplishments of their activities 
available to the research community and to the public at large.
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    \1\ NIH's mission is to seek fundamental knowledge about the 
nature and behavior of living systems and the application of that 
knowledge to enhance health, lengthen life, and reduce illness and 
disability. See http://www.nih.gov/about/mission.htm.
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    The results of NIH funded research can be disclosed in a number of 
ways, including through publications, presentations at scientific 
meetings, sharing research tools, and depositing information into 
databases and materials into repositories. NIH has a number of policies 
that promote the dissemination of research results and guide funding 
recipients in disseminating their results. The NIH Data Sharing Policy, 
the NIH Public Access Policy, the NIH Research Tools Policy, and the 
NIH Genomic Data Sharing Policy are important examples of policies to 
ensure that research data and materials generated using NIH funds are 
used productively to further scientific progress and to promote public 
health.\2\ Increasing public access to information from NIH research 
supports the public access and data sharing directives of the Executive 
Office of the President (EOP Directives).\3\
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    \2\ See http://www.grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm; http://publicaccess.nih.gov/; http://grants.nih.gov/grants/intell-property_64FR72090.pdf; and http://gds.nih.gov/03policy2.html.
    \3\ See the Office of Science and Technology Policy's 
memorandum, ``Increasing Access to the Results of Federally Funded 
Scientific Research,'' (February 22, 2013), the Office of Management 
and Budget's memorandum, ``Open Data Policy--Managing Information as 
an Asset,'' M-13-13 (May 9, 2013) http://www.whitehouse.gov/sites/default/files/omb/memoranda/2013/m-13-13.pdf, and Executive Order 
No. 13,642 (May 9, 2013) http://www.thefederalregister.org/fdsys/pkg/DCPD-201300318/pdf/DCPD-201300318.pdf.
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    Traditionally, scientists fulfill their obligation to contribute to 
the general body of knowledge through peer reviewed journal 
publications. However, journal publication is not always possible, and 
many clinical trials are not being published or published in a timely 
manner. A recent study found that the results of less than half of NIH-
funded clinical trials had been published in a peer-reviewed biomedical 
journal within 30 months of trial completion.\4\ Selective publication 
of the results of some trials and not others--or publication of 
incomplete or partial findings from a particular trial--can lead to 
inappropriate conclusions about the usefulness of particular 
therapies.\5\
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    \4\ Ross JS, Tse T, Zarin DA, Xu H, Zhou L, Krumholz HM. 
Publication of NIH funded trials registered in ClinicalTrials.gov: 
cross-sectional analysis. BMJ. 2012;344:d7292.
    \5\ Nissen S, Biomarkers in Cardiovascular Medicine, The Shame 
of Publication Bias, JAMA Intern Med 2013 March 25; doi:10.001/
jamainternmed.2013.4074; Dwan K et al., Systematic review of the 
empirical evidence of study publication bias and outcome reporting 
bias, PLoS One 2008 Aug 28;3(8):e3081. doi: 0.1371/
journal.pone.0003081; Begg C, Berlin J, Publication bias and 
dissemination of clinical research, J Natl Cancer Inst 1989, Jan 
18;81(2):107-15.
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    Public access to clinical trial information drives scientific 
progress and optimizes the return on the nation's investment in 
clinical trials. It helps inform future research, improve study design, 
and prevent duplication of unsafe and unsuccessful trials. In addition, 
there is an important ethical dimension to dissemination of clinical 
trial results because individuals who volunteer to participate in such 
studies, and who may assume risks, trust that what we learn will 
contribute to generalizable knowledge about human health. Finally, 
enhancing transparency also increases public trust in clinical 
research. It is, therefore, important to provide other ways for 
clinical trial results to be disseminated and publicly available to 
researchers, health care providers, and patient communities.
    Some NIH-funded clinical trials are subject to mandatory 
registration and reporting of results under federal law, i.e., Title 
VIII of the Food and Drug Administration Amendments Act of 2007 
(FDAAA). FDAAA applies, in general, to controlled, interventional 
studies of Food and Drug Administration (FDA)-regulated drugs, 
biological products, and devices, excluding phase 1 studies of drugs 
and biological products and small feasibility studies of devices. Under 
FDAAA, a minimal set of summary information about such clinical trials 
must be submitted in a structured, tabular format to 
ClinicalTrials.gov, a freely accessible and searchable registry and 
results data bank operated by the National Library of Medicine (NLM), 
NIH.
    NIH is proposing to issue a policy to ensure that all NIH-funded 
clinical trials are registered and have summary results, including 
adverse event information, submitted to ClinicalTrials.gov. Compliance 
with this policy will be a term and condition in the Notice of Grant 
Award and a contract requirement in the Contract Award. This proposed 
policy supports the NIH mission and is essential to facilitate the 
translation of research results into knowledge, products, and 
procedures that improve human health.

Request for Comments

    NIH encourages the public to provide comments on any aspect of the 
draft policy, described below. Comments should be submitted 
electronically to the Office of Clinical Research and Bioethics Policy 
(OCRBP), Office of Science Policy, NIH, via email at email at 
[email protected], mail at 6705 Rockledge 
Drive, Suite 750, Bethesda, MD 20892, or by fax at 301-496-9839. 
Submitted comments are considered public information; private or 
confidential information should not be submitted. Comments may be 
posted along with the submitter's name and affiliation on the OCRBP Web 
site after the public comment period closes.

Draft NIH Policy on Dissemination of NIH-Funded Clinical Trial 
Information

    Purpose. The purpose of this Policy is to promote broad and 
responsible dissemination of information from NIH-funded clinical 
trials through ClinicalTrials.gov, the clinical trial registry and 
results databank operated by the National Library of Medicine (NLM). 
Disseminating this information supports the NIH mission to advance the 
translation of research results into knowledge, products, and 
procedures that improve human health. This Policy is intended to 
complement the statutory mandate under Title VIII of the Food and Drug 
Administration Amendments Act of 2007 (FDAAA) that requires 
registration and submission of summary results for certain clinical 
trials, whether funded by NIH or by other entities, to be registered 
and have summary results submitted to ClincalTrials.gov.\6\
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    \6\ The mandate applies to certain ``applicable clinical 
trials'' (ACTs) of drugs (defined by section 402(j)(1)(A)(vii) of 
the Public Health Service Act to include biological products) and 
devices, including any pediatric postmarket surveillance of a device 
required by FDA under section 522 of the Federal Food, Drug, and 
Cosmetic Act (FD&C Act). See 42 U.S.C. 282(j).
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    Scope and Applicability. This Policy applies to all NIH-funded 
awardees and investigators conducting clinical trials, funded in whole 
or in part by NIH, regardless of study phase, type of intervention, or 
whether they are subject to the FDAAA registration and results 
submission requirements set forth in Section 402(j) of the Public 
Health Service Act (42 U.S.C. 282(j)). For

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purposes of this Policy, a clinical trial is defined as ``a research 
study in which one or more human subjects are prospectively assigned to 
one or more interventions (which may include placebo or other control) 
to evaluate the effects of those interventions on health-related 
biomedical or behavioral outcomes.\7\''
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    \7\ Several terms within the NIH definition of clinical trial 
definition mean are defined as follows. ``Research'' and ``human 
subject'' are defined in the Common Rule at 45 CFR 46.102(d) and 45 
CFR 46.102(f), respectively. ``Prospectively assigned'' refers to a 
pre-defined process (e.g., randomization) specified in an approved 
protocol that stipulates the assignment of research subjects 
(individually or in clusters) to one or more arms (e.g., 
intervention, placebo or other control) of the clinical trial. An 
``intervention'' is defined as a manipulation of the subject or 
subject's environment for the purpose of modifying one or more 
health-related biomedical or behavioral processes and/or endpoints. 
Examples include drugs/small molecules/compounds; biologics; 
devices; procedures (e.g., surgical techniques); delivery systems 
(e.g., telemedicine, face-to-face interviews); strategies to change 
health-related behavior (e.g., diet, cognitive therapy, exercise, 
development of new habits); treatment strategies; prevention 
strategies; and, diagnostic strategies. A ``health-related 
biomedical or behavioral outcome'' is defined as the pre-specified 
goal(s) or condition(s) that reflect the effect of one or more 
interventions on human subjects' biomedical or behavioral status or 
quality of life. Examples include positive or negative changes to 
physiological or biological parameters (e.g., improvement of lung 
capacity, gene expression); positive or negative changes to 
psychological or neurodevelopmental parameters (e.g., mood 
management intervention for smokers; reading comprehension and/or 
information retention); positive or negative changes to disease 
processes; positive or negative changes to health-related behaviors; 
and, positive or negative changes to quality of life. See http://osp.od.nih.gov/office-clinical-research-and-bioethics-policy/clinical-research-policy/clinical-trials>
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    Effective Date. This Policy is effective for:
     Competing grant applications that include clinical trials 
and are submitted to the NIH for the [date to be determined] receipt 
date and subsequent receipt dates;
     Proposals for contracts that include clinical trials and 
are submitted to the NIH on or after [date to be determined]; and
     NIH intramural research projects that include clinical 
trials for which Institutional Review Board review is initiated after 
[date to be determined].
    Responsibilities. As set forth in the terms and conditions of grant 
and contract awards, all NIH-funded awardees and investigators 
conducting clinical trials, funded in whole or in part by NIH, who have 
committed to NIH that they will comply with NIH policies, are expected 
to ensure that their NIH-funded clinical trials are registered and 
summary results, including adverse event information, are submitted to 
ClinicalTrials.gov in accord with the timelines that will be set forth 
at ClinicalTrials.gov. Generally, this means registration of the 
clinical trial not later than 21 days after enrollment of the first 
participant and submission of summary results information not later 
than one year after the completion date. ``Completion date'' is defined 
to be the date that the final subject was examined or received an 
intervention for the purpose of final collection of data for the 
primary outcome, whether the clinical trial concluded according to the 
pre-specified protocol or was terminated. It will be possible to delay 
results submission for up to two years beyond the initial deadline with 
a certification that regulatory approval of the product is being 
sought. Clinical trials covered by the policy will be expected to 
submit the same type of registration and results data and in the same 
timeframes as the trials subject to FDAAA. The specific registration 
and results information to be submitted will be made available at the 
ClinicalTrials.gov site.
    Institutions and investigators should submit information directly 
to ClinicalTrials.gov. If the trial is subject to FDAAA, i.e., section 
402(j) of the Public Health Service Act (42 U.S.C. 282(j)), submissions 
must be made by the Responsible Party, as defined at 42 U.S.C. 
282(j)(1)(A)(ix). If an NIH-funded clinical trial is also subject to 
FDAAA, it needs to have only one entry in ClinicalTrials.gov that 
contains its registration and results information. Investigators and 
funding recipients are expected to cooperate with NLM to address any 
data curation or quality control issues to facilitate timely posting.
    In general, NIH expects to make clinical trial registration and 
results information publicly available through ClinicalTrials.gov 
within 30 days after receipt by ClinicalTrials.gov.\8\ For NIH-funded 
trials that are subject to section 402(j) of the Public Health Services 
Act (42 U.S.C. 282(j)), submitted information will be posted in 
compliance with the relevant requirements of that section.
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    \8\ For clinical trials funded through SBIRs, the timeframe for 
posting results will be consistent with the SBIR Policy Directive, 
which generally prohibits the agency from posting SBIR data for at 
least 4 years from completion of the study unless the awardee 
consents to an earlier release. See SBIR Policy Directive, Sections 
8(b)(2) and (4).
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    Failure to comply with the terms and conditions of NIH awards may 
provide a basis for enforcement actions, including termination, 
consistent with 45 CFR 74.62 and/or other authorities, as 
appropriate.\9\
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    \9\ When the final policy is issued, NIH will also provide more 
specific procedural guidance to facilitate implementation.

     Dated: January 8, 2015.
Lawrence Tabak,
Principal Deputy Director, National Institutes of Health.
[FR Doc. 2015-02994 Filed 2-12-15; 8:45 am]
BILLING CODE 4140-01-P