1. Tulane University Office of Research Compliance
ClinicalTrials.gov at Tulane University How Does it Affect Me? What Do I Need to Know?
Tulane University Office of Research Compliance
October 21, 2016

2. Be aware that…
Any PowerPoint presentation can only be an introduction to a topic.
This subject is complex – this will point you to many other resources – and our office is happy to assist you further.
PowerPoint bullets are neither the law nor the regulations that apply.
All information contained herein is detailed more fully in the Tulane Policies and Procedures for ClinicalTrials.gov Registration and Reporting Results.

3. Learning Objectives
Explain what ClinicalTrials.gov is and what it can do
Explain what studies must be registered
FDAAA
CMS
ICMJE
NIH
Identify who is responsible for registration
Noncompliance penalties
Setting up an Account with ClinicalTrials.gov
Help Resources
Table of Contents
Overview of the ClinicalTrials.gov system – history and purposes: Slides 4-8
Recent Changes: Slide 9
Studies required by FDAAA to be registered and results reported: Slides 10–14
Studies required by CMS to be registered: Slides 15-16
Studies to be registered to meet ICMJE policy: Slides 17-19
Studies required by NIH to be registered and results reported: Slides 20-21
Overview of requirements: Slide 22
Identify who is responsible for registration and results reporting (Responsible Party): Slides 23-26
Penalties for non-registration and results reporting: Slides 27-28
Required language in Informed Consent Document: Slides 29 – 31
Setting up an Account with ClinicalTrial.gov: Slides
Resources: Slides

4. What is ClinicalTrials.gov?
Why should I be concerned?

6. ClinicalTrials.gov is the national registry of federally and privately supported research studies conducted in the United States and around the world.
The U.S. National Institutes of Health (NIH), through its National Library of Medicine (NLM), has developed this site in collaboration with the Food and Drug Administration (FDA), as a result of the FDA Modernization Act, which was passed into law in November 1997.
The basic rationale for ClinicalTrials.gov is that it can be a tool to improve transparency and reduce duplication of effort.
While each study is updated in real time, there is also an archive feature that allows the public to see the history of changes to the record.

7. Rationale Increase research transparency Help people find trials
Reduce duplication of effort
Please see detailed explanations of the value of transparency from Dr. Deb Zarin’s Presentation Overview of ClinicalTrials.gov located at
– Public knows how its money is being spent;
– Quicker and wider public access than some publications provide
– Suppression of research results impedes the scientific process in all areas of science
– Trials Results inform the public’s medical decisions
– Unacknowledged changes are made to the trial protocol that would affect the interpretation of findings
– Publications do not always include all prespecified outcome measures
– Provide a place where researchers can see what is going on elsewhere – even before results exist, to avoid duplication of effort
To learn more, visit:

8. NIH
Updated from D. Zarin, ClinicalTrials.gov, Overview of ClinicalTrials.gov presentation, December 2008,

9. Recent News
On September 16, 2016, the Public Health Service issued a “Final Rule,” 45 CFR Part 11, expanding the requirements for registration and submission of results with ClinicalTrials.gov for “Applicable Clinical Trials.”
Effective date of final rule: January 18, 2017
Institutions/PIs will have until April 19, 2017 to become compliant
Tulane will issue a revised policy and accompanying training materials to reflect the provisions of the Final Rule.

10. Why should I register a trial in ClinicalTrials.gov?

11. # 1 It’s the law! FDA Amendments Act of 2007 (FDAAA)
Most prospective clinical trials involving regulated drugs, biological products, and devices must be registered on ClinicalTrials.gov. (The law also requires reporting of results and adverse events for a subset of these studies.)
To learn more about FDAAA 801 Requirements, visit:

12. It’s the law (a final detail)
Some Phase I trials, though they are not Applicable Clinical Trials under FDAAA , are required to register under FDAMA – the earlier law -- which is still in effect.
These involve primarily experimental treatments for serious or life-threatening diseases whether using an IND, Group C Cancer drug, or other FDA regulated product.
Thus, many studies for cancer and other serious and life-threatening diseases must register regardless of Phase.
For more information:
Some examples of serious and life-threatening diseases that FDAMA would apply to in addition to cancer are: AIDS and ALS

13. FDAAA - Registration Required for “Applicable Clinical Trials”:
Interventional studies (drugs, biologics, devices)
Phase 2 – 4 (not phase 1 drug; not small feasibility device;)
US FDA jurisdiction (e.g., IND/IDE or US site)
Studies initiated after September 27, 2007, or initiated on or before that date and were still ongoing as of December 26, 2007
Not required for observational studies.
When:
Within 21 days of enrollment of 1st subject
Update at least every 12 months (30 days for Recruitment Status and Primary Completion Date)
The following are also not applicable clinical trials: observational studies; single patient expanded access (treatment IND), Small clinical trials to determine the feasibility of a device or a clinical trial to test prototype devices, where the primary outcome measure relates to feasibility and not to health outcomes.
See Tulane ClinicalTrials.gov Policy ( section on “Registration Exclusions”

14. FDAAA – Results Submission
Required for:
Applicable Clinical Trials
In which the study product is approved (for any use) by FDA
When:
Within 12 months of Primary Completion Date (final data collection for primary endpoint)
If product not approved by Primary Completion Date but is approved later, then results due 30 days after approval
Delays are possible, primarily for manufacturer or under limited special circumstances
Pending publication is NOT considered a good cause for delay
The Primary Completion Date may be well before the PI thinks the study is over. There may be additional follow-up that continues for years – but ClinicalTrials.gov wants results data submitted within a year of the final data collection for the primary endpoint. That means getting to work on analysis and reporting quickly.
Acceptable delays MAY but not automatically be granted:
If you are the manufacturer seeking initial approval
If you are the manufacturer seeking approval for a new use
If you are granted an extension of time for “good cause”.

15. #2 Centers for Medicare & Medicaid Services (CMS) Billing Rule
When a trial is registered in ClinicalTrials.gov, ClinicalTrials.gov assigns the trial a National Clinical Trial Number (“NCT#”).
Effective January 1, 2014, CMS requires mandatory reporting of the NCT# on claims for items and services provided in “qualified clinical trials” for Medicare coverage.
See ]

16. CMS: What is a “qualifying trial”? *
Purpose of trial must be the evaluation of an item/service that falls within Medicare benefit category (e.g. physicians’ service, durable medical equipment, diagnostic test)
Trial must have therapeutic intent
Trial must enroll patients with diagnosed disease and not only healthy volunteers
* This slide represents a summary definition. For a complete definition, see Medicare NCD at

17. International Committee of Medical Journal Editors (ICMJE)
#3 You Want to Publish!
International Committee of Medical Journal Editors (ICMJE)
Requires registration in a publicly available, searchable system such as ClinicalTrials.gov.
Scope is broader than FDAAA (i.e., all clinical trials).
Includes journals that have adopted the ICMJE policy, such as BMJ, JAMA, and NEJM.
For more info, see:
To be precise, ICMJE doesn’t require registration in ClinicalTrials.gov, but in any of several international registries, WHO, or European Studies registry. ClinicalTrials.gov is just the most obvious, easy and logical for our researchers, since they may have to post there for government reasons anyway.
The list of journals following ICMJE’s Uniform Requirements for Manuscripts Submitted to Biomedical Journals (URM) is available on the ICMJE website, The URM includes the obligation to register clinical trials. There may be some journals that follow the ICMJE recommendations, but have never requested a listing on the ICMJE webpage. There may be some listed journals that do not follow all of the many recommendations and policies in the document. Authors and others with questions about the processes or policies of a specific journal should consult that journal directly.

18. ICMJE – Registration: Which studies?
Required for Prospective studies that:
Assign subjects to an intervention or concurrent comparison or control groups
Study the cause/effect relationship between medical intervention
and a health outcome.
ICMJE scope is much broader than the scope of FDAAA:
Interventions include procedures, behavioral treatments, dietary interventions
Health outcomes include any biomedical or health-related measure obtained in participants, including pharmacokinetic measures and adverse events
Important to note both the broader definition and also the fact that ICMJE policy says results reporting won’t be seen as prior publication.
All Phase I studies are included: because they involve safety and pharmacokinetic measures. Also, whereas FDAAA has exclusions for small feasibility studies of devices, ICMJE does not – and does not accept a study registered and using the lock box to be considered registered because it’s not public!
As with ClinicalTrials.gov, observational studies do not need to be included.
Source:

19. ICMJE - Registration
ICJME policy requires registration of all prospective clinical trials in a World Health Organization-approved primary registry such as ClinicalTrials.gov.
When to register:
Prior to enrollment of 1st subject
ICJME policy does not require, but encourages, reporting of clinical trial results in clinicaltrials.gov.
For more detailed information, see the ICJME Editorial, “Is This Clinical Trial Fully Registered? — A Statement from the International Committee of Medical Journal Editors.”
There are several databases that one can use to comply with ICMJE. For example European studies can use EudraCT.  EudraCT is a confidential data base accessible to the European Medicines Agency (EMA) and national EU regulatory bodies.  Data entry is done by the sponsor into an XML file, the file is uploaded to the database by the national EU regulatory bodies. Another EU database is EuCTR, a public database started after The studies have to be conducted in the EU, Phases 2-4 in adults, and all pediatric population studies Phase 1-4. 
Other acceptable databases are listed at the ICMJE FAQs:

20. #4 The Trial is or will be NIH funded
The NIH encourages registration and results reporting for all NIH-supported clinical trials, regardless of whether or not they are subject to FDAAA. All clinical trials, regardless of study phase or type of intervention, that are funded by grant applications, contracts, or other transactions submitted to NIH on or after January 18, 2017, must register and report results with ClinicalTrials.gov.
Source:

21. **NEW** NIH REQUIREMENTS
NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information (“NIH Policy”)
All clinical trials, regardless of study phase or type of intervention, that are funded by grant applications, contracts, or other transactions submitted to NIH on or after January 18, 2017, must register and report results with ClinicalTrials.gov.
Applies to all clinical trials funded in whole or part by NIH, whether or not the trial is subject to the FDAAA
Requires compliance with FDAAA 801 in progress reports for any NIH grant that supports a clinical trial, even if the grantee is not the Responsible Party for registering trials and submitting trial results to ClinicalTrials.gov.
Applications for NIH funding for any clinical trial submitted on or after January 18, 2017,must include as part of the application a plan for registering trials and submitting results to ClinicalTrials.gov.
For detailed information, see NIH Definition of Clinical Trial, Summary of HHS/NIH Initiatives to Enhance Availability of Clinical Trial Information, NIH Clinical Research Policy, NIH Definition of Clinical Trial, and NIH Policy p. 22.
NIH Definition of a Clinical Trial: “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.”

22. Reasons to Register in Clinicaltrials.gov
Increasing Recruitment
NIH policy
2016
FDAAA Results & AE
Reporting
FDAAA and FDAMA Registration
FDAAA:
Registration: All Phase 2-4 drug, biologic, and devices trials regulated by FDA
Results Reporting: Phase 2 – 4 trials using an FDA approved drug, biologic, or device
ICMJE:
Registration: All phases, all interventions
No results reporting .
ICMJE Registration

24. Who is responsible for registering the trial?
The FDAAA and NIH Policy require the “Responsible Party” to register and submit results to clinicaltrials.gov.
FDAAA
The Responsible Party (RP) defined as…
The Sponsor (or Sponsor-Investigator);
IND/IDE holder
If no IND/IDE, the industry, academic institution or other organization that initiated the study
-or-
The PI if so designated by a sponsor, grantee, contractor, or awardee (check sponsoring agreement/contract)
NIH Policy
The agreement/contract with the sponsor should designate who the Responsible Party is for the trial (consult the terms and conditions of the award as to who the RP is).
ICMJE
Anyone can register, but for ICMJE the author is responsible for ensuring complete registration
Technically, the grantee of a federal grant is the responsible party – so the university may be the responsible party, but the law allows delegation of the Responsible Party role to the individual PI. Some institutions have actual contracts they require the PI to sign before receiving the first payment, accepting responsibility as the responsible party. Others just have that “assumed”.

25. FDAAA: Designation of Responsible Party (RP)
RP can be designated by the Sponsor to a PI who
Is responsible for conducting the study
Has access to and control over the data
Has the right to publish the trial results, AND
Has the ability to meet the requirements
Example of RP designation
PI initiated study at Tulane funded by NHLBI
Tulane is the grant funding recipient.
Tulane designates the PI as the RP
Note: even if not designated as RP, the PI can still enter data into ClinicalTrials.gov for the trial.

26. Who is the Responsible Party (RP)?
If a trial is being conducted under an IND or IDE, then the IND/IDE holder is the RP, regardless of how the trial is funded.
If the IND/IDE is issued in the name of the PI, the PI is the RP.
If the IND/IDE is issued in the name of the sponsor of the research, the sponsor of the research is the RP.
For trials not conducted under an IND or IDE at Tulane:
Contractual agreements with industry/pharmaceutical sponsors of trials typically designate the industry/pharmaceutical sponsor as the RP.
Government (federal and state) funded grants designate the grant recipient, Tulane Univ., as the Responsible Party. However, Tulane delegates this responsibility to the PI, making the PI the RP.
Where no external funding exists for the trial, the PI is the RP by default.
Exceptions exist. Check the agreement/contract with the sponsor (or the grant’s terms and conditions) regarding who is responsible for trial registration and results submission to ClinicalTrials.gov. Tulane Sponsored Projects Administration (SPA) can assist with providing a copy of the agreement/contract/grant if needed.
For more detailed information, see ClinicalTrials.gov: Requirements and Implementation Strategies and Identifying the "Responsible Party" under FDAAA for Applicable Clinical Trials Conducted Under NIH Grants.
By “law” (FDA regulation), when the trial is conducted under an IND or IDE, the IND/IDE holder is the Responsible Party. So, that is what we have to look to first. If the PI holds the IND/IDE, PI is RP. If sponsor holds the IND/IDE, sponsor is RP. Where a trial is not conducted under an IND or IDE, the contractual agreement/grant can designate the RP. For industry sponsored, Tulane negotiates for the industry sponsor to be the RP. For federal awards, the award designates the grant recipient, Tulane Univ., as the RP. However, Tulane in turn delegates this responsibility to the PI.

27. What happens if I don’t register?

28. Consequences of Noncompliance
FDAAA - Registration & Results Reporting
Public notices of noncompliance and violations
Withholding of grant funds
FDA sanctions
Civil monetary penalties (up to $10,000/day)
ICMJE - Registration
Cannot publish in journals following ICMJE policy, and
other select journals
NIH Policy - Registration & Results Reporting
Withholding of NIH funds
Termination of grant(s)
Food and Drug Administration Amendments Act of Public Law No ,
Section 801. p. 99 of 156 of Public Law /27/2007
(b) CONFORMING AMENDMENTS.—
(1) PROHIBITED ACTS.—Section 301 of the Federal Food,
Drug, and Cosmetic Act (21 U.S.C. 331) is amended by adding
at the end the following:
‘‘(jj)(1) The failure to submit the certification required by section
402(j)(5)(B) of the Public Health Service Act, or knowingly submitting
a false certification under such section.
‘‘(2) The failure to submit clinical trial information required
under subsection (j) of section 402 of the Public Health Service
Act.
‘‘(3) The submission of clinical trial information under subsection
(j) of section 402 of the Public Health Service Act that
is false or misleading in any particular under paragraph (5)(D)
of such subsection (j).’’.
(2) CIVIL MONEY PENALTIES.—Subsection (f) of section 303
of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 333),
as redesignated by section 226, is amended—
(A) by redesignating paragraphs (3), (4), and (5) as
paragraphs (5), (6), and (7), respectively;
(B) by inserting after paragraph (2) the following:
‘‘(3)(A) Any person who violates section 301(jj) shall be subject
to a civil monetary penalty of not more than $10,000 for all violations
adjudicated in a single proceeding.
‘‘(B) If a violation of section 301(jj) is not corrected within
the 30-day period following notification under section 402(j)(5)(C)(ii),
the person shall, in addition to any penalty under subparagraph
(A), be subject to a civil monetary penalty of not more than $10,000
for each day of the violation after such period until the violation
is corrected.’’
Source: ICMJE: Clinical Trial Registration; FDAA 801 Requirements; NIH Policy, pp

29. What are the requirements for informed consent language?

30. FDA Requirements – Informed Consent
Pursuant to FDA Guidance, the following exact statement must be included in the informed consent documents of Applicable Clinical Trials:
“A description of this clinical trial will be available on as required by US law. This website will not include information that can identify you. At most, the website will include a summary of the results. You can search this website at any time.”
By federal regulation, the required language must be incorporated verbatim and cannot be altered in any way.
However, the statement can only be used if the trial is an “Applicable Clinical Trial” required by the FDA to post in ClinicalTrials.gov. If not, do not used this statement.
For detailed information, see FDA regulatory guidance at

31. NIH Requirements - Informed Consent
NIH Policy:
Informed consent documents for clinical trials funded by NIH must include a specific statement relating to posting of clinical trial information with ClinicalTrials.gov.
Applies to clinical trials funded by NIH resulting from applications for funding submitted on or after January 18, 2017,
Source: NIH Policy p. 23.

32. How do I set up an account with ClinicalTrials.gov?
Let’s practice!

33. Directions
A user account is needed to register trials and report results.
If you do not have an account, proceed to ClinicalTrials.gov:
Click on “Submit Studies”, then click on “How to Apply for an Account”.
Towards the bottom of the webpage, click on the link “PRS Administer Contact Request Form”. Complete the contact request form for the appropriate Organization (Tulane University).
You will receive an from clinicaltrials.gov with the address for the Tulane University Protocol Registration System (PRS) Administrator, the Tulane PRS Administrator account at and request that the Administrator assign a user name and password to you.
You must complete the PRS Administrator Contact Request Form in clinicaltrials.gov in order to establish an account. An account cannot be created if this step is skipped.
Tip: If you do not know if you have an account or have forgotten your username, use the same steps as above to verify your username.

34. Help for Registering Studies on ClinicalTrials.gov
“Submit Studies”
“For Researchers”
“For Study Record Managers”

35. Tips & Available Recourses
The Tulane Clinical Translational Unit (“CTU”) assists with clinicaltrials.gov registration and results reporting on clinicaltrials.gov on a fee-for-service basis.
For further information, contact Rachel Cruthirds or  
ClinicalTrials.gov contains a link at the bottom of each webpage in order to submit a ticket for help: “CONTACT NLM HELP DESK”.
ClinicalTrials.gov may be contacted with questions or for guidance via at
If the question is about a specific study record, please provide the NCT Number or the Unique Protocol ID (if an NCT Number has not yet been assigned).
Be detailed in your request.
Tulane ClinicalTrials.gov Registration & Reporting Results Policies and Procedures
Available at
Here’s the citation for the guidance.

36. What if I have more questions?

37. Tulane Contact Information
Tulane PRS Administrator:
Tulane Research Compliance Office:
Tulane Clinical Translational Unit:

38. Additional Resources General ClinicalTrials.gov information
FDAAA related information
For specific questions or comments
Office of Extramural Research (OER)
Frequently Asked Questions for NIH Grantees
Instructions for Authors sections of ICMJE journals all have information regarding clinical trial registration
NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information
Final Rule on Clinical Trials Registration and Results Information Submission
Summary of the NIH Policy and the Final Rule: