[Federal Register Volume 81, Number 183 (Wednesday, September 21, 2016)]
[Notices]
[Pages 64922-64928]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-22379]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


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

AGENCY: National Institutes of Health, Department of Health and Human 
Services.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The National Institutes of Health (NIH) is issuing this policy 
to promote broad and responsible dissemination of information from NIH-
funded clinical trials through ClinicalTrials.gov. The policy 
establishes the expectation that all investigators conducting clinical 
trials funded in whole or in part by the NIH will ensure that these 
trials are registered at ClinicalTrials.gov, and that results 
information of these trials is submitted to ClinicalTrials.gov.

DATES: This policy will take effect January 18, 2017.

FOR FURTHER INFORMATION CONTACT: For information about the policy, 
please contact the NIH Office of Science Policy at 
[email protected].

SUPPLEMENTARY INFORMATION: The policy is complementary to the statutory 
and regulatory reporting requirements. These are section 402(j) of the 
Public Health Service Act, as amended by Title VIII of the Food and 
Drug Administration (FDA) Amendments Act of 2007 (FDAAA), and the 
regulation Clinical Trial Registration and Results Information 
Submission, at 42 CFR part 11. Hereafter, we refer to section 402(j) as 
the statute and 42 CFR part 11 as the rule or regulation.
    On November 19, 2014, and in tandem with the publication of the 
Notice of Proposed Rulemaking (NPRM) on Clinical Trial Registration and 
Results Submission, the NIH issued a complementary draft policy for 
public comment on the Dissemination of NIH-funded Clinical Trial 
Information [Ref. 1, 2]. The draft policy proposed that all NIH-funded 
awardees and investigators conducting clinical trials, funded in

[[Page 64923]]

whole or in part by the NIH, regardless of study phase, type of 
intervention, or whether they are subject to the statutory registration 
and results information submission requirements, would be expected to 
ensure that those clinical trials are registered and results 
information is submitted to ClinicalTrials.gov. It further stated that 
submission of the same type of registration and results information 
would be expected and in the same timeframes as the trials subject to 
the statute, and that this information would be made publicly available 
through the ClinicalTrials.gov Web site.
    The NIH received approximately 240 public comments on its proposed 
policy. The comments came from a range of stakeholders including 
researchers, academic/research institutions, medical practitioners, 
patients, patient/disease advocacy groups, scientific/professional 
societies and associations, device manufacturers, trade associations, 
not-for-profit non-governmental organizations, and the general public 
[Ref. 3]. The NIH appreciated the public interest in the proposed 
policy and the time made and effort taken by stakeholders to provide 
comments. The NIH carefully considered those comments in the 
development of the final policy. In the next section, we provide an 
overview of the comments on the proposed policy. Because those in 
compliance with the policy would be expected to follow specific 
provisions of the rule, a number of commenters on the policy reiterated 
comments that they submitted to the docket in response to the NPRM 
[Ref. 4]. Since these comments are discussed at length in the preamble 
of the rule, we are limiting the discussion of comments here primarily 
to those that identified issues specific to the policy, such as its 
scope, applicability, and impact on NIH-funded awardees and 
investigators.

Overview of the Public Comments

    A significant majority of the public comments were supportive of 
the proposed NIH policy and of its application to the full range of 
NIH-funded clinical trials. Most commenters appreciated the impetus 
behind the policy and agreed that it was important to provide ways 
other than journal publication for clinical trial results to be 
disseminated and made publicly available to researchers, health care 
providers, and patient communities. They recognized that increased 
availability of information from NIH-funded clinical trials would help 
researchers by informing the design and development of their future 
studies, address the needs of patients and healthcare providers seeking 
information about NIH-funded trials, and serve the public's interest by 
preventing duplication of unsafe and unsuccessful trials and mitigating 
publication bias. They also agreed that improving the availability of 
clinical trial information will strengthen the public's trust in 
biomedical research as well as assure volunteers that their 
participation in clinical trials has advanced knowledge on human health 
and disease. A number of commenters also suggested that the policy is 
particularly appropriate because NIH-funded clinical trials are 
supported by public funding, and recipients of those funds have a 
special obligation to ensure that the nation's investment is maximized.
    A number of comments from academic investigators and stakeholder 
organizations were supportive of the policy and its goals. Others, 
however, disagreed with the policy, suggesting that it was ill-advised 
and/or unnecessary. These commenters suggested that the benefit of 
greater transparency was outweighed by the burden and cost of the 
policy to those who conduct clinical trials and that the NIH had not 
made a sufficient case for the policy or that it was not evidence-
based. Some commenters suggested that the NIH should simply encourage 
investigators to be more transparent or that the NIH's public access 
policy made the policy unnecessary since it requires NIH-funded 
investigators to make their published articles publicly available 
through PubMed Central.
    Scope and Applicability of the Policy. Although the majority of 
commenters fully supported the scope of the policy, i.e., that it 
should apply to NIH-funded clinical trials of FDA-regulated drugs 
regardless of phase, small feasibility studies of devices, and trials 
of interventions not regulated by FDA, including surgical and 
behavioral interventions, there were comments suggesting that the scope 
was too narrow, or conversely, too broad.
    One commenter suggested that the policy ought to encompass more 
detailed summary results, such as Clinical Study Reports, as well as 
de-identified individual patient-level data. One commenter suggested 
that the NIH should consider extending the policy to preclinical in 
vivo (laboratory) animal studies because the arguments for the 
registration and required reporting of preclinical in vivo (laboratory) 
animal studies are similar to those of human clinical trials. Some 
commenters suggested that the policy should be retroactive and apply to 
clinical trials that are underway as of the policy's effective date as 
well as those that have already been completed as of the effective 
date.
    On the other hand, there were other comments suggesting that the 
policy should not apply to phase 1 or so called phase 0 trials, pilot 
trials designed to examine the feasibility of an approach, trials 
mounted by an investigator at a small organization, or trials that are 
unable to enroll a statistically significant number of participants. 
One suggested that even pilot trials that reach their enrollment target 
should not be expected to submit results information because the 
results might be more misleading than helpful. Another proposed that 
reporting on phase 1 clinical trials should be limited to adverse 
events information because these trials are designed to assess safety 
rather than efficacy, and reporting non-safety outcomes could be 
misleading. Another suggested that clinical trials not covered under 
the statute should not submit adverse event information unless a 
regulatory authority or equivalent body has first performed an analysis 
of the event in order to prevent public misunderstanding. Another 
commenter suggested that submission of data from early phase research 
could divert limited research resources and time from phase 3 studies. 
Another suggested that only information about phase 3 clinical trials 
should be included in ClinicalTrials.gov because information about 
early stage trials could confound, rather than enhance, public 
understanding of human health and could, thereby, inadvertently 
adversely affect patient safety.
    One commenter suggested that the policy should apply only to the 
registration of clinical trials, not the submission of results 
information. This commenter asserted that registration information was 
sufficient because any interested party could follow up with an 
investigator to learn more about the trial and because submission of 
registration information takes a fraction of the time needed to submit 
results information.
    There were a few commenters who took issue with the application of 
the policy to trials that are only partially funded by the NIH. They 
asserted that the policy would entail the disclosure of confidential 
commercial information and that the NIH's authority to do so is limited 
to a trial that is wholly NIH-funded and involves a product with 
research and development costs wholly government-funded. A few other 
commenters suggested that the policy should exclude clinical trials 
that use NIH-supported infrastructure, but involve no NIH funds.

[[Page 64924]]

    NIH Definition of Clinical Trial. Some commenters addressed the NIH 
definition of clinical trial, which is key to determining the policy's 
applicability. There was support for the breadth of the definition, 
i.e., encompassing all interventional studies with biomedical outcomes 
(e.g., pharmacokinetic and behavioral outcomes, as well as health-
related outcomes). One commenter, however, thought more elaboration on 
the definition was needed to clarify the meaning of ``health-related 
biomedical or behavioral outcomes.'' They thought that without such 
specificity, the definition might be interpreted to exclude studies 
that contain valuable information for public health research, science, 
and clinical medicine. Commenters believed that addressing this issue 
would be vital to ensure a common understanding that the NIH policy 
applies to all clinical trials involving a biomedical or behavioral 
intervention. Another suggested that a study involving only one 
participant should not be considered a clinical trial since a trial 
with a sample size of one would not provide any valid data to share 
with the public.
    Some commenters noted that the wording of the NIH definition was 
not identical to the wording of the definition of clinical trial in the 
proposed rule or to how other organizations, e.g., the World Health 
Organization (WHO), International Committee of Medical Journal Editors 
(ICMJE), and Centers for Medicare & Medicaid Services (CMS), use the 
term. They were concerned that investigators would have difficulty 
understanding their obligations under the policy and under the rule and 
in meeting requirements of others. They called for reconciliation of 
any actual or apparent differences in the definitions.
    A commenter urged the NIH to issue guidance to help determine 
whether a study is a clinical trial under the definition and to clarify 
how disagreements in the matter would be resolved and communicated.
    Results Information Submission Timeline. A few commenters raised 
concerns about the proposed rule's timeline for reporting results 
information, asserting that 12 months after the primary completion date 
of the clinical trial (i.e., the date of final data collection for the 
primary outcome measure) is too soon, particularly for NIH-funded 
academic investigators. These commenters suggested that academic 
investigators will have more difficulty meeting the timeframe because 
they must also spend time teaching, fulfilling clinical care 
responsibilities, and writing grant applications. Another commenter 
suggested that a 12-month timeframe would also be more challenging for 
academic investigators because, unlike industry investigators, they 
generally cannot count on support from a central administrative service 
to help them carry out their reporting responsibilities. 
Decentralization of information in academic centers would also present 
a particular challenge to those covered by the NIH policy, according to 
another commenter, who also suggested that the mobility of new 
investigators may make it difficult to meet timelines. These commenters 
urged the NIH to allow a longer submission timeframe, e.g., 18 or 24 
months. A few noted that providing more time would also give 
investigators time to prepare journal publications, and one also 
expressed concern about the possibility that journal editors will begin 
to consider submission of results information to ClinicalTrials.gov as 
prior publication, which could thwart journal publication altogether.
    Structured Results Data Elements. A few commenters suggested that 
the data submission structure, which is determined by the provisions of 
the statute, does not work well for clinical trial types that will be 
covered only the policy, e.g., phase 1 trials of drugs/biologics, small 
feasibility device studies, trials of social and behavioral 
interventions, or those with non-standard designs. These commenters 
thought that other fields would need to be added to the 
ClinicalTrials.gov to enable investigators to report data elements for 
those trials appropriately and accurately. They also suggested 
increasing the character limit on data fields to allow for more careful 
and nuanced explanations. Commenters also suggested that if the 
ClinicalTrials.gov cannot accommodate these types of trials, 
investigators should be exempted from the policy. One commenter 
requested that an additional data element should be included to allow 
an investigator to indicate that the trial's hypothesis had been 
confirmed.
    Protecting Privacy. One commenter raised a concern about the 
policy's impact on the privacy of clinical trial participants 
suggesting that it might be easy to re-identify participants in many 
NIH-funded pilot studies with small sample sizes. The commenter pointed 
to the five percent threshold for non-serious adverse events and site 
location information as the data elements creating the vulnerability. 
The commenter urged the NIH to allow an investigator to obtain a waiver 
from results information submission where participant privacy was at 
risk.
    Compliance Issues. The proposed policy noted that compliance with 
the policy would be a term and condition of award and that non-
compliance may provide a basis for enforcement actions, including 
termination. A few commenters discussed the importance of compliance. 
One suggested that the NIH should take compliance records into account 
when considering future applications for funding. They suggested that 
such an approach could be more effective than terminating funding of a 
current grant since most of the research may already be completed. 
Another thought that making compliance a term and condition of award 
was important and that it would incentivize good behavior and help 
change attitudes about the value of enhancing availability of clinical 
trial information.
    Other commenters raised concerns about the costs that will be 
incurred by NIH-funded academic institutions to ensure that clinical 
investigators are following the policy. They suggested institutions 
will need to provide more administrative support and other resources to 
help investigators comply and that this would be difficult given the 
indirect cost cap of 26 percent. Commenters urged the NIH to allow the 
time and effort required for ClinicalTrials.gov compliance to be 
included as a direct cost on NIH grants. Another commenter suggested 
that the increased results information submissions brought on by the 
NIH policy will stretch the NIH's capabilities and that it will be 
important for the NIH to ensure that sufficient resources are available 
to manage high volume data uploads and customer service requests.

NIH Policy

    The NIH considered all the comments received on the proposed policy 
as well as those that were submitted in response to the NPRM. There was 
overwhelming support for both the proposed policy and the NPRM, 
particularly among concerned citizens, scientific societies, medical 
practitioners, and individual scientists. There were also concerns 
expressed, particularly in the comments from academic commenters. We 
appreciate those concerns and understand that the policy will create 
additional work for many investigators. However, we believe that the 
work should not be seen as a burden, but, rather, an inherent part of 
an investigator's commitment to the advancement of science. The 
benefits will, in the long run, accrue to the investigators as well as 
to the public, patients, and the enterprise as a whole because 
transparency will improve

[[Page 64925]]

future research designs and maximize the public's investment--and their 
trust--in research. Equally important, it will help investigators 
fulfill the ethical obligation they have to clinical trial 
participants, namely to ensure that the findings from their 
participation contribute to generalizable knowledge and the advancement 
of public health.
    As we noted in the preamble to the proposed policy, 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. The NIH 
awardees have always been expected to make the results of their 
activities available to the research community and to the public at 
large because it is intrinsic to the scientific process. In research 
involving human beings, moreover, scientists also have an ethical 
obligation to ensure that the burden and risk that volunteers assume by 
participating in research comes to something, at the very least by 
ensuring that others are aware of the study and that its findings 
contribute to the advancement of human health.
    We disagree with commenters who suggested that there is no need for 
coverage of certain types of trials, such as early exploratory trials, 
small trials, trials assessing only safety, or trials that terminate 
before reaching enrollment targets. The benefits of transparency and 
the need to fulfill the ethical obligation to participants is as 
relevant to these types of trials as to any other type. We were also 
not persuaded that the timeframe for results information submission 
should be longer for academic investigators because of their competing 
responsibilities or that they should be allowed more time to publish 
their results in a journal. The timeframe of 12 months from the primary 
completion date should provide enough time for investigators to 
organize their data and submit results information. We are also 
confident that academic institutions can develop central support 
services as necessary to assist investigators should they need it. We 
also believe that 12 months represents an appropriate balance between 
investigators' interests and the interests of the public in having 
access to the results of a publicly funded trial. In addition, it will 
be possible to delay results information submission for up to two years 
beyond the initial deadline with a certification that regulatory 
approval of the trial product is being sought.
    Some commenters suggested that a policy on clinical trial 
information dissemination is not needed because it duplicates other NIH 
policies. This policy is certainly in keeping with our principles, 
longstanding expectations, and other policies as well as the more 
recent broad policy call for scientific agencies to increase public 
access to scientific data [Ref. 5]. However, it does not duplicate any 
other NIH policy, nor does any other NIH policy accomplish what this 
one will.
    Some commenters also contended that this policy is not necessary 
because the results of clinical trials will be published or because 
they can be obtained via direct requests to the trial's principal 
investigator. In fact, research has shown that the results of a 
significant portion of clinical trials are not published or published 
in a timely manner. For example, a 2012 study of NIH-funded clinical 
trials found that after a median of 51 months following trial 
completion, 32 percent were unpublished [Ref. 6]. A more recent study 
of the trial publication rate among 51 U.S. academic medical centers 
found that 43 percent of their clinical trials were unpublished two 
years after the trial was completed [Ref. 7]. While the ability to seek 
results information from the original investigator is useful to 
facilitate collaborations, to access individual-level data, and to gain 
insights from those who conducted the trial, it is not a surefire way 
to increase access to trial results nor is it efficient or transparent, 
particularly for the public.
    We believe that the public availability of clinical trial results 
information will be beneficial to all parties in the long run, 
including those who are covered by this policy. All investigators stand 
to benefit from this policy. For example, science may progress more 
quickly because investigators will be able to learn from trials to 
which they otherwise would not have had access because they were 
unpublished. In addition, the public availability of results 
information helps investigators design trials and Institutional Review 
Boards (IRBs) review proposed trials, by allowing them to weigh the 
proposed study's risks and benefits against a more complete evidence 
base than is currently available through the scientific literature 
[Ref. 8]. Submission and posting of results information will also help 
investigators avoid repeating trials on interventions that have been 
found to be unsafe or unsuccessful while also providing access to 
information that may help verify findings.
    For all of these reasons, we have not changed the essential 
contours of the policy. In terms of scope, the policy still applies to 
all NIH-funded awardees and investigators conducting clinical trials 
funded in whole or in part by the NIH regardless of study phase, type 
of intervention, or whether they are subject to the statute and to the 
rule. It clarifies that the policy is an expectation, that applicants 
and offerors are required to submit a plan outlining how they will meet 
the policy's expectations, and, that upon receipt of an award, an 
awardee will be obligated to adhere to their plan through the terms and 
conditions of the award. The required plan can be a brief statement 
explaining whether the applicant/offeror intends to register and submit 
results information to ClinicalTrials.gov as outlined in the policy or 
to meet the expectations in another manner. It is important to remember 
that an NIH-funded clinical trial that meets the definition of an 
applicable clinical trial is subject to the regulation and, therefore, 
register and submission of results information to ClinicalTrials.gov is 
a requirement.
    The policy applies to both the extramural and intramural programs. 
For the NIH extramural program, the policy applies to applications for 
funding including for grants, other transactions, and contracts 
submitted on or after the policy's effective date that request support 
for the conduct of a clinical trial that is initiated on or after the 
policy's effective date. This means that the policy does not apply to 
clinical trials in ongoing, non-competing awards, but that it will 
apply if the grantee submits a competing renewal application that 
includes a new clinical trial, i.e., a clinical trial initiated on or 
after the effective date of the policy. For the intramural program, the 
policy applies to clinical trials initiated on or after the policy's 
effective date. The policy's effective date is January 18, 2017. The 
policy clarifies that a clinical trial that uses NIH-supported 
infrastructure, but does not receive NIH funds to support its conduct, 
is not subject to the policy.
    The policy outlines the responsibilities for NIH-funded 
investigators according to whether the trial is covered by the policy 
only or also the rule. For those covered by the policy only, NIH-funded 
awardees and investigators will be expected to submit the same 
registration and results information in the same timeframes as those 
subject to the statute and rule. The timeline for registration is not 
later than 21 calendar days after the enrollment of the first 
participant. The standard timeline for results information is not later 
than one year after the trial's primary completion date, but the policy 
also allows for delayed submission of results information in certain

[[Page 64926]]

circumstances for up to two additional years for trials of products 
regulated by the FDA that are unapproved, unlicensed, or uncleared or 
for trials of products for which approval of a new use is being sought.
    Although the policy does not apply to NIH-funded clinical trials 
initiated before the effective date, we encourage all ongoing NIH-
funded clinical trials to follow it. It is also critical for 
investigators conducting NIH-funded applicable clinical trials that are 
subject to the statute and rule to be sure they are in compliance with 
those requirements.
    The policy continues to use the NIH definition of ``clinical 
trial'' as proposed in the draft policy to determine which research 
studies are covered by the policy. This definition was developed in 
2014 to reflect the NIH research mission and the scope of clinical 
trials within the NIH portfolio. With regard to the concern expressed 
by a public commenter that the phrase ``health-related biomedical or 
behavioral outcomes'' might be too narrow, we note that the definition 
considers biomedical and behavioral outcomes to be health-related 
outcomes in interventional studies that meet the other components of 
the definition. Also, regarding the concern that the wording of the 
definitions of clinical trial in this policy and the rule differ, this 
is so mainly in reference to outcomes, i.e., the NIH definition 
explicitly references behavioral outcomes whereas the definition in the 
rule encompasses them within the term ``health related.'' These 
distinctions are not significant in terms of defining what is covered 
by the NIH policy. All NIH-funded clinical trials, whether they are 
assessing biomedical or behavioral outcomes or whether they are 
employing an FDA regulated product, are covered by the policy. An NIH-
funded clinical trial assessing a behavioral intervention that is not 
regulated by the FDA would meet both definitions of clinical trial, 
and, thereby, be covered by the policy. However, such a trial would not 
be subject to the rule because it does not meet the rule's definition 
of ``applicable clinical trial.'' Guidance available on the NIH's Web 
site can help awardees and investigators understand whether a research 
study is a clinical trial for purposes of the NIH policy (see first Web 
site listed below). Questions should be directed to the NIH program 
staff. To understand whether an NIH-funded clinical trial is also 
subject to the statute and the rule, awardees and investigators should 
look to the rule's definition of ``applicable clinical trial.''
    NIH-funded awardees and investigators will be expected to follow 
the provisions of the rule in terms of when they register their trials, 
what information they provide as part of the registration process, when 
they submit their results information, and what results information is 
submitted. All of the alternate approaches in the rule will also be 
available to those covered by the policy, e.g., for delayed posting of 
device registration information, delayed submission of results 
information for trials involving unapproved products or products for 
which a new use is sought, extensions for good cause, and waivers that 
might be needed for privacy or national security reasons.
    With regard to the concern that ClinicalTrials.gov is not set up to 
accept NIH-funded trials that are small or exploratory in nature or 
involve behavioral interventions, it is important to note that the 
ClinicalTrials.gov does accommodate the submission of all trial types 
and that a variety of study and trial types have been entered into 
ClinicalTrials.gov since its inception. In addition, ClinicalTrials.gov 
has resources available to assist investigators in navigating the 
registration and results information submission processes. These 
resources will continue to be updated over time to be responsive to 
investigators' needs and the evolving clinical research enterprise. 
Therefore, it should not be necessary for a clinical investigator of an 
NIH-funded clinical trial to seek an exemption from the policy for 
reasons related to the capacity of ClinicalTrials.gov to accommodate 
all types of clinical trials.
    Registration and results information submission to 
ClinicalTrials.gov complements publication of trial results in peer-
reviewed scientific journals. Information submitted to 
ClinicalTrials.gov is displayed in a structured way and includes a 
complete list of all pre-specified outcome measures and all adverse 
events. Journal articles, on the other hand, typically focus on a 
select set of outcome measures and adverse events and include 
background and discussion of the implications of the results. 
Information submitted to ClinicalTrials.gov undergoes a quality control 
review whereas journal articles will be peer reviewed. With regard to 
the concern that submission of results could make journal publication 
more difficult or impossible, the ICMJE has stated that submission of 
summary results to ClinicalTrials.gov will not be considered prior 
publication and will, thus, not interfere with journal publication 
[Ref. 9]. We encourage all NIH-funded investigators to publish the 
results of their studies in peer-reviewed journals.
    We have no doubt that this policy will be beneficial for the 
research community as well as the public generally, but we recognize 
that adhering to it will be a new obligation. We will provide 
additional guidance to facilitate implementation and help awardees and 
investigators understand the policy as well as the tasks described in 
the rule that they will be expected to undertake. In terms of the costs 
of complying with the policy, grantees are permitted to charge the 
salaries of administrative and clerical staff as a direct cost [Ref. 
10]. Such staff could assist investigators in meeting their 
responsibilities under the policy. In addition, administrative costs 
can be covered through indirect cost recovery.
    We intend for this policy to benefit all communities who seek 
information about NIH-funded clinical trials, and we are confident that 
the benefits of transparency will become evident soon after the policy 
is implemented. We plan to evaluate the implementation and impact of 
the policy from the perspective of those who comply with it as well as 
from the perspective of ClinicalTrials.gov users, including patients, 
providers, and investigators.
    We look forward to engaging with NIH-funded investigators and 
awardees as they work to meet the expectations of this important public 
policy. Information to assist applicants, offerors, and investigators 
is available at the following Web sites. The NIH will continue to add 
guidance materials to these sites as the policy's implementation 
continues.

     http://osp.od.nih.gov/office-clinical-research-and-bioethics-policy/clinical-research-policy/clinical-trials
     https://clinicaltrials.gov/ct2/manage-recs
     http://grants.nih.gov/clinicaltrials_fdaaa/faq.htm

    The NIH policy is set forth below.

References

1. National Institutes of Health, U.S. Department of Health and 
Human Services, NIH request for public comments on the proposed NIH 
policy on dissemination of NIH-funded clinical trial information. 
NIH Guide for Grants and Contracts. 2014 Nov 19. Available from 
https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-019.html. 
Also published in Fed Regist. 2015 Feb 13; 80(30):8096-98. Available 
from https://www.federalregister.gov/articles/2015/02/13/2015-02994/announcement-of-a-draft-nih-policy-on-dissemination-of-nih-funded-clinical-trial-information.
2. National Institutes of Health, U.S.

[[Page 64927]]

Department of Health and Human Services, Notice of Proposed 
Rulemaking on Clinical Trials Registration and Results Submission. 
Fed Regist. 2014 Nov 21;79(225):69566-69680. Available from https://www.federalregister.gov/articles/2015/02/13/2015-02990/clinical-trials-registration-and-results-submission.
3. A compilation of public comments on the draft NIH Policy on 
Dissemination of NIH-Funded Clinical Trial Information is available 
at: http://osp.od.nih.gov/sites/default/files/resources/Clinical%20Trials%20Dissemination%20Policy%20Combined%20Comments_2.0.pdf.
4. U.S. Department of Health and Human Services, National Institutes 
of Health, National Library of Medicine. Clinical Trials 
Registration and Results Submission. [Internet]. 2011 [cited 2016 
September 1]. Available from: https://www.regulations.gov/docket?D=NIH-2011-0003.
5. NIH Data Sharing Policy (https://grants.nih.gov/grants/policy/data_sharing/); NIH Public Access Policy (https://publicaccess.nih.gov/policy.htm or https://publicaccess.nih.gov/); 
NIH Genomic Data Sharing Policy (https://gds.nih.gov/03policy2.html); Increasing Access to the Results of Federally 
Funded Scientific Research (https://www.whitehouse.gov/sites/default/files/microsites/ostp/ostp_public_access_memo_2013.pdf).
6. Ross et al., BMJ. 2012 Jan 3;344:d7292. http://www.bmj.com/content/bmj/344/bmj.d7292.full.pdf.
7. Chen et al., BMJ. 2016 Feb 17;352:i637 http://www.bmj.com/content/bmj/352/bmj.i637.full.pdf.
8. Berlin, JA, et al., Bumps and Bridges on the Road to Responsible 
Sharing of Clinical Trial Data. Clinical Trials. 2014;11:7-12.
9. ICMJE [Internet]. International Committee of Medical Journal 
Editors; 2016. Clinical trial registration; 2011 [cited 2016 Aug 5]; 
[about 2 screens]. Available from: http://www.icmje.org/recommendations/browse/publishing-and-editorial-issues/clinical-trial-registration.html and http://www.icmje.org/about-icmje/faqs/clinical-trials-registration/.
10. 45 CFR 75.413(c) and Chapter 8.1.1.6, Direct Charging Salaries 
of Administrative and Clerical Staff. NIH Grants Policy Statement. 
http://grants.nih.gov/grants/policy/nihgps/HTML5/section_8/8.1_changes_in_project_and_budget.htm.

NIH Policy on Dissemination of NIH-Funded Clinical Trial Information

Purpose

    The National Institutes of Health (NIH) Policy on Dissemination of 
NIH-funded Clinical Trial Information establishes the expectation that 
all NIH-funded awardees and investigators conducting clinical trials, 
funded in whole or in part by the NIH, will ensure that their NIH-
funded clinical trials are registered at, and that summary results 
information is submitted to, ClinicalTrials.gov for public posting.\1\ 
The purpose of the policy is to promote broad and responsible 
dissemination of information from NIH-funded clinical trials through 
ClinicalTrials.gov. Disseminating this information supports the NIH 
mission to advance the translation of research results into knowledge, 
products, and procedures that improve human health.
---------------------------------------------------------------------------

    \1\ ClinicalTrials.gov is operated by the National Library of 
Medicine within the NIH.
---------------------------------------------------------------------------

    This policy is complementary to requirements in the Clinical Trial 
Registration and Results Information Submission regulation at 42 CFR 
part 11, hereinafter referred to as the regulation.\2\ Clinical trials 
that are subject to the regulation are, in general, clinical trials of 
drug, biological, and device products regulated by the Food and Drug 
Administration (FDA), except phase 1 trials of drug and biological 
products and small feasibility studies of device products. A pediatric 
post-market surveillance study of a device product required by the FDA 
is also subject to the regulation. Clinical trials subject to the 
regulation are generally called ``applicable clinical trials.'' 
Applicable clinical trials are required to be registered in 
ClinicalTrials.gov not later than 21 calendar days after the enrollment 
of the first participant. Results information from those trials 
generally must be submitted not later than one year after the trial's 
primary completion date. Submission of results information can be 
delayed in certain circumstances for up to two additional years for 
trials of products regulated by the FDA that are unapproved, 
unlicensed, or uncleared or for trials of products for which approval, 
licensure, or clearance of a new use is being sought.
---------------------------------------------------------------------------

    \2\ The Clinical Trial Registration and Results Information 
Submission regulation at 42 CFR part 11 was issued in the Federal 
Register in September 2016. The regulation implements section 402(j) 
of the Public Health Service Act.
---------------------------------------------------------------------------

Scope and Applicability

    This policy applies to all NIH-funded clinical trials regardless of 
study phase, type of intervention, or whether they are subject to the 
regulation. For example, NIH-funded phase 1 clinical trials of an FDA-
regulated product are covered by this policy as are clinical trials 
studying interventions not regulated by the FDA, such as behavioral 
interventions. As such, the policy encompasses all NIH-funded clinical 
trials, including applicable clinical trials subject to the regulation. 
All NIH-funded clinical trials will be expected to register and submit 
results information to ClinicalTrials.gov.
    This policy applies to clinical trials funded in whole or in part 
through the NIH extramural and intramural programs. For the NIH 
extramural program, the policy applies to applications for funding 
including for grants, other transactions, and contracts submitted on or 
after the policy's effective date that request support for the conduct 
of a clinical trial that is initiated on or after the policy's 
effective date. For the NIH intramural program, the policy applies to 
clinical trials initiated on or after the policy's effective date.
    This policy does not apply to a clinical trial that uses NIH-
supported infrastructure but does not receive NIH funds to support its 
conduct.

Responsibilities

    As part of their applications or proposals, applicants and offerors 
seeking NIH funding will be required to submit a plan for the 
dissemination of NIH-funded clinical trial information that will 
address how the expectations of this policy will be met. NIH-funded 
awardees and investigators conducting clinical trials funded in whole 
or in part by the NIH will be required to comply with all terms and 
conditions of award, including following their plan for the 
dissemination of NIH-funded clinical trial information.
    Consistent with those terms and conditions, the responsibilities of 
such awardees and investigators will fall within one of the three 
categories. The category depends on whether, under the regulation, the 
clinical trial is also an ``applicable clinical trial'' and the awardee 
or investigator is the ``responsible party.''
    1. If the NIH-funded clinical trial is an applicable clinical trial 
under the regulation and the awardee or investigator is the responsible 
party, the awardee or investigator will ensure that all regulatory 
requirements are met.
    2. If the NIH-funded clinical trial is an applicable clinical trial 
under the regulation but the awardee or investigator is not the 
responsible party, the awardee or investigator will coordinate with the 
responsible party to ensure that all regulatory requirements are met.
    3. If the NIH-funded clinical trial is not an applicable clinical 
trial under the regulation, the awardee or investigator will be 
responsible for carrying out the tasks and meeting the timelines 
described in regulation. Such tasks include registering the clinical 
trial in ClinicalTrials.gov and submitting results information to 
ClinicalTrials.gov.

[[Page 64928]]

    In addition, informed consent documents for clinical trials within 
all three categories are to include a specific statement relating to 
posting of clinical trial information at ClinicalTrials.gov.
    Each NIH-funded clinical trial should have only one entry in 
ClinicalTrials.gov that contains its registration and results 
information. Awardees and investigators need not and should not create 
a separate record of the applicable clinical trial to comply with this 
policy.
    The NIH will publicly post registration information and results 
information in ClinicalTrials.gov.

Definitions

    Clinical Trial. For purposes of this policy, a ``clinical trial'' 
means ``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.'' 
\3\ This definition encompasses phase 1 trials of FDA-regulated drug 
and biological products, small feasibility studies of FDA-regulated 
device products, and studies of any intervention not regulated by the 
FDA, e.g., behavioral interventions. This definition of ``clinical 
trial'' \4\ is broader than the term ``applicable clinical trial'' as 
defined in the regulation.\5\
---------------------------------------------------------------------------

    \3\ Further information about this definition is available from 
the NIH Office of Science Policy at http://osp.od.nih.gov/office-clinical-research-and-bioethics-policy/clinical-research-policy/clinical-trials.
    \4\ Note that the regulation also includes a definition of 
``clinical trial.'' That definition is ``a clinical investigation or 
a clinical study in which human subject(s) are prospectively 
assigned, according to a protocol, to one or more interventions (or 
no intervention) to evaluate the effect(s) of the intervention(s) on 
biomedical or health related outcomes'' (see 42 CFR 11.10 (a)). For 
the purposes of this policy, the regulatory definition and the 
definition in this policy are treated as synonymous.
    \5\ In the regulation, applicable clinical trial is defined as 
an applicable device clinical trial or an applicable drug clinical 
trial. The regulation defines an applicable device clinical trial to 
mean, in part, ``a prospective clinical study of health outcomes 
comparing an intervention with a device product subject to section 
510(k), 515, or 520(m) of the Federal Food, Drug, and Cosmetic Act 
(21 U.S.C. 360(k), 21 U.S.C. 360e, 21 U.S.C. 360j(m)) against a 
control in human subjects (other than a small clinical trial to 
determine the feasibility of a device product, or a clinical trial 
to test prototype device products where the primary outcome measure 
relates to feasibility and not to health outcomes).'' The regulation 
defines an applicable drug clinical trial to mean, in part, ``a 
controlled clinical investigation, other than a phase 1 clinical 
investigation, of a drug product subject to section 505 of the 
Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355) or a biological 
product subject to section 351 of the Public Health Service Act (42 
U.S.C. 262), where ``clinical investigation'' has the meaning given 
in 21 CFR 312.3 (or any successor regulation) and ``phase 1'' has 
the meaning given in 21 CFR 312.21 (or any successor regulation).''
---------------------------------------------------------------------------

    Responsible Party. In the policy, the awardee or the investigator 
is responsible for meeting the expectations of this policy. In the 
regulation, a ``responsible party'' means, in part, ``with respect to a 
clinical trial, the sponsor of the clinical trial, as defined in 21 CFR 
50.3 (or any successor regulation); or the principal investigator of 
such clinical trial if so designated by a sponsor, grantee, contractor, 
or awardee, so long as 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 under [42 CFR part 11] 
for the submission of clinical trial information.'' \6\
---------------------------------------------------------------------------

    \6\ See 42 CFR 11.10 (a) and 42 CFR 11.4.
---------------------------------------------------------------------------

    Primary Completion Date. In the policy, this term has the same 
meaning as the term ``primary completion date'' in the regulation, 
which is ``the date that the final subject was examined or received an 
intervention for the purposes of final collection of data for the 
primary outcome, whether the clinical trial concluded according to the 
pre-specified protocol or was terminated.'' \7\
---------------------------------------------------------------------------

    \7\ See the complete definition at 42 CFR 11.10 (a).
---------------------------------------------------------------------------

    Registration Information. In the policy, this term has the same 
meaning as the term ``registration information'' in the regulation. In 
the regulation, registration information consists of descriptive 
information, recruitment information, location and contact information, 
and administrative data.\8\
---------------------------------------------------------------------------

    \8\ See 42 CFR 11.10 (b) and 42 CFR 11.28 for the specific data 
elements.
---------------------------------------------------------------------------

    Results Information. In the policy, this term has the same meaning 
as the term ``results information'' in the regulation. In the 
regulation, results information includes participant flow, demographic 
and baseline characteristics, outcomes and statistical analyses, 
adverse events, the protocol and statistical analysis plan, and 
administrative information.\9\
---------------------------------------------------------------------------

    \9\ See 42 CFR 11.28 for complete results information and 
specific data elements.
---------------------------------------------------------------------------

Compliance

    If the clinical trial is NIH-funded in whole or in part, 
expectations for clinical trial registration and summary results 
submission will be included in the terms and conditions of the award. 
Failure to comply with the terms and conditions of the NIH award may 
provide a basis for enforcement actions, including termination, 
consistent with 45 CFR 75.371 and/or other authorities, as appropriate. 
If the NIH-funded clinical trial is also an applicable clinical trial, 
non-compliance with the requirements specified in 42 U.S.C. 282(j) and 
42 CFR part 11 may also lead to the actions described in 42 CFR 11.66.

Effective Date

    This policy is effective January 18, 2017.

    Date: September 12, 2016.
Francis S. Collins,
Director, National Institutes of Health.
[FR Doc. 2016-22379 Filed 9-16-16; 11:15 am]
 BILLING CODE 4140-01-P