August 2020

Purpose:

The purpose of this Policy is to outline the requirements for clinical trials registration and results reporting on ClinicalTrials.gov and expectations for Johns Hopkins Medicine (JHM) investigator adherence with these requirements. Additionally, this policy outlines the requirements for posting of clinical trial informed consent forms for federally funded clinical trials where the posting requirement will be fulfilled through ClinicalTrials.gov.

Who is Governed By This Policy:

Johns Hopkins Medicine Faculty who serve as Principal Investigators (PIs) of a clinical trial [as defined below].

Defining Clinical Trials:

The definition of clinical trial differs across federal policies, regulations and other sources. For the purposes of this policy JHM has established that, if a study meets the International Committee of Medical Journal Editors (ICMJE) definition of a clinical trial, it will be considered a clinical trial and requires registration on ClinicalTrials.gov.

International Committee of Medical Journal Editors (ICMJE) Definition of Clinical Trial:

“The ICMJE defines a clinical trial as any research project that prospectively assigns people or a group of people to an intervention, with or without concurrent comparison or control groups, to study the relationship between a health-related intervention and a health outcome. Health-related interventions are those used to modify a biomedical or health-related outcome; examples include drugs, surgical procedures, devices, behavioral treatments, educational programs, dietary interventions, quality improvement interventions, and process-of-care changes.”

Studies That Require Registration:

JHM has established that any study that meets the International Committee of Medical Journal Editors (ICMJE) definition of a clinical must be registered on the ClinicalTrials.gov Protocol Registration and Results System (PRS).

Studies That Require Results Reporting:

JHM has established that clinical trials meeting any of the following criteria shall both be registered and have results reported on the ClinicalTrials.gov Protocol Registration and Results System (PRS):

1) Clinical Trials funded either in whole, or in part by the National Institutes of Health (NIH) with grant applications submitted on or after January 18, 2017

Institutes of Health (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.

If you answer YES to ALL four of the following questions, your study is considered a clinical trial per the NIH definition:

1. Does the study involve human participants?
2. Are the participants prospectively assigned to an intervention?
3. Is the study designed to evaluate the effect of the intervention on the participants?
4. Is the effect being evaluated a health-related biomedical or behavioral outcome?

Your study is considered to meet the NIH definition of a clinical trial even if:

• Your study uses healthy participants, or does not include a comparison group (e.g., placebo or control)
• Your study is only designed to assess the pharmacokinetics, safety, and/or maximum tolerated dose of an investigational drug
• Your study utilizes a behavioral intervention
• Your study uses an intervention for the purposes of understanding fundamental aspects of a phenomenon (See guidance and FAQs about Basic Experimental Studies with Humans [BESH]).

Your study is NOT considered to meet the NIH definition of a clinical trial if:

• Your study is intended solely to refine measures.
• Your study involves secondary research with biological specimens or health information

2) Qualifying clinical trials which will render claims for items and services to the Center for Medicare and Medicaid Services (CMS):

The National Clinical Trial (NCT) number must be included on claims for items and services provided in clinical trials that are qualified for coverage as specified in the "Medicare National Coverage Determination (NCD) Manual," Section 310.1

3) Studies supported by a foundation who is a signatory to the May 18, 2017 WHO, International Clinical Trials Registry Platform (ICTRP):

Many Non-governmental organizations (NGOs) and foundations such as the Bill and Melinda Gates Foundation, and the Wellcome Trust require registration and results reporting.

 

4) “Applicable Clinical Trials” (ACTs) subject to registration and reporting requirements under the Food and Drug Administration’s Amendments Act (FDAAA) which include the following:

 

• Trials of Drugs/Biologics: Controlled, clinical investigations of a product subject to FDA regulations. This includes preliminary studies or phase I trials to be published in an ICMJE journal.
• Trials of Devices: Controlled trials with health outcomes, other than small feasibility studies, and pediatric post-market surveillance.
• The trial has one or more sites in the U.S.
• The trial is conducted under an FDA Investigational New Drug Application (IND) or Investigational Device Exemption (IDE) application
• The trial involves a drug, biologic, or device that is manufactured in the U.S. or its territories and is exported for research

Trials that are excluded:

 

• (Non-serious/life-threatening) Phase 1 drug trials, including studies in which drugs are used as research tools to explore biological phenomena or disease processes
• 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
• Trials that do not include drugs, biologics, or devices (e.g., behavioral interventions)
• Non-interventional (observational) clinical research, such as cohort or case-control studies
• Trials that were ongoing* as of September 27, 2007, and reached the Completion Date before December 26, 2007

*An “ongoing” trial has enrolled one or more subjects and the final subject has not been examined or received an intervention for the purpose of collecting data on the primary outcome.

When To Register Studies:

JHM has established that for any trial subject to registration requirements the registration must be completed at or before first participant enrollment.

Requirements For Updating ClinicalTrials.gov Records:

All studies registered on ClinicialTrials.gov must be continually kept up-to-date and accurate as follows:

• Records must be reviewed and verified at least once-a-year, even if there are no changes to the study
• The following data elements must be updated within 30 days after a change occurs:
  • Study start date
  • Intervention name(s)
  • Availability of Expanded Access
  • Expanded Access status
  • Overall recruitment status
  • Explanation for change in status
  • Actual enrollment data
  • Individual site status
  • IRB status
  • Completion Date
  • Responsible Party
  • Official Title
  • Contact Information

When To Submit Results To ClinicalTrials.gov:

It is the responsibility of the PI to submit the trial results through ClinicalTrials.gov in accordance with the following timelines;

• Results for the primary outcome measure(s) must be submitted no later than 12 months after the primary completion date (The date that the final participant was examined or received an intervention for the purposes of final collection of data for the primary outcome).
   
• Results for the secondary outcome measure(s) must be submitted no later than 12 months after the study completion date (The date the final participant was examined or received an intervention for purposes of final collection of data for the primary and secondary outcome measures and adverse events (for example, last participant’s last visit).

Uploading The Informed Consent Form To ClinicalTrials.gov:

Per the Revised Common Rule section §46.116, a copy of an approved consent form used to enroll participants must be uploaded to ClinicalTrials.gov for all federally-funded research that was initially approved by the IRB on or after January 21, 2019.

• The PI must ensure that one IRB-approved informed consent form used to enroll subjects is posted
• The PI must ensure that any redactions are approved by the Federal department or agency supporting or conducting the trial
• The PI must ensure that the informed consent form is uploaded to ClinicalTrials.gov or a docket folder on Regulations.gov
• The informed consent form must be uploaded after the clinical trial is closed to recruitment, and no later than 60 days after the last study visit by any subject, as required by the protocol.

Other Policy Requirements:
 

1. The “Unique Protocol ID” must be the IRB number in ClinicalTrials.gov
2. Any grant/funding number(s) must be listed as a “Secondary ID” (if applicable)
3. A PRS Administrator will assign the PI as “Record Owner”
4. The “Responsible Party” must be designated as the “Sponsor”
5. Each PRS user will have their own account. Account sharing is not allowed.

Penalties/Consequences:

On August 12, 2020 the Food and Drug Administration (FDA) released the final guidance on Civil Money Penalties Relating to the ClinicalTrials.gov Data Bank.

Johns Hopkins Investigators should review the guidance and be aware of the following;

• Failure to submit trial results information or the submission of false or misleading information may lead to civil monetary penalty and/or withholding of or loss of current and future grant funding
• Failure to submit a required certification or knowingly submitting a false certification to the FDA may lead to civil monetary penalty
• Failure to adhere to clinical trial registration and results submission compliance rules may lead to posting of Notice of non-compliance by FDA and NIH

If a violation is identified, a preliminary notice of noncompliance will be issued to the responsible party for the applicable record(s). Failure to comply with the requirements relating to applicable clinical trials may result in further FDA regulatory action, including the issuance of a Notice of Noncompliance, civil money penalties, injunction, and/or criminal prosecution.

If a violation is not corrected within 30 days, an initial civil money penalty of not more than $12,103 may be assessed. An additional $12,103 may be assessed for each day until the violation is corrected

Addressing Notices of Noncompliance:

Should any Johns Hopkins Investigator receive a “Preliminary Notice of Noncompliance (Pre-Notice) Letter” from Clinicaltrials.gov, they should immediately contact the Johns Hopkins University ClinicalTrials.gov Program at [email protected].

JHM Clinical Trials.Gov Program staff will report receipt of the notification to ICTR leadership, the Office of General Council and the Institutional Review Board as well as applicable departmental leadership. Program staff will work with the investigator to review the trial(s) cited by the letter to resolve any potential violations fully and within 30 calendar days.

Any civil monetary penalties will be paid by the Investigator’s Department/Division.

Should any investigator receive any notice related to ClinicalTrials.gov during an FDA inspection, they should immediately contact the Johns Hopkins University ClinicalTrials.gov Program at [email protected].

Definitions:

Access List: A list of account holders within the PRS that are granted access to a study. A user granted access to a record in this manner can perform all of the same actions on the record as if they were the record owner, with the exception of modifying the Record Access List.

NCT Number: The National Clinical Trial number is an identification that ClinicalTrials.gov assigns a study when it is registered. The NCT number is in the format “NCTXXXXXXXX”. Until an NCT number is assigned, the study is not registered.

PRS: The Protocol Registration and Results System is the online system that allows account holders within the institution to register, update and report results on ClinicalTrials.gov. The PRS can be accessed at https://register.clinicaltrials.gov. JHM maintains separate PRS accounts for “JohnsHopkinsU”, “SKCCC”, “KennedyKrieger” and “JHSPH”

Record Owner: Any account holder that creates a new record is automatically assigned as the Record Owner. The Record Owner will receive periodic emails from ClinicalTrials.gov whenever there are problems that require attention.

Responsible Party: The sponsor of the clinical study, as defined in 21 CFR 50.3; or the principal investigator of such clinical study if so designated by a sponsor, grantee, contractor, or awardee, so long as the principal investigator is responsible for conducting the study, has access to and control over the data from the clinical study, has the right to publish the results of the study, and has the ability to meet all of the requirements for the submission of clinical study information. For a pediatric post-market surveillance of a device product that is not a clinical trial, the responsible party is the entity who FDA orders to conduct the pediatric post-market surveillance of the device product.

The sponsor may designate a principal investigator as the responsible party if such principal investigator meets all of the following requirements: is responsible for conducting the study; has access to and control over the data from the study; has the right to publish the results of the study; and has the ability to meet all of the requirements for submitting and updating clinical study information.

Secondary ID: Any identifier(s), other than the organization's Unique Protocol ID or the NCT number that is assigned to the clinical study. This includes any unique clinical study identifiers assigned by other publicly available clinical trial registries. If the clinical study is funded in whole or in part by a U.S. Federal Government agency, the complete grant or contract number must be submitted as a Secondary ID.

Sponsor: The entity (for example, corporation or agency) that initiates the study

Unique Protocol ID: Any unique identifier (ID) assigned to the protocol by the sponsor. At JHU, the Unique Protocol ID is the IRB number.

Related Resources:

• • University Policies/Guidelines:
    Posting of Consent Forms for Federally-Funded Clinical Trials https://www.hopkinsmedicine.org/institutional_review_board/guidelines_policies/guidelines/posting_cf_federally_funded_clinical_trials.htm
    Organization Guidelines on Registration of Clinical Trials
  • External Policies/Guidelines:
    ICMJE Recommendations For Clinical Trial Registration And Data Sharing http://www.icmje.org/recommendations/browse/publishing-and-editorial-issues/clinical-trial-registration.html

To contact the Johns Hopkins ClinicalTrials.gov program, please e-mail [email protected] or visit https://ictr.johnshopkins.edu/clinicaltrials-gov

For further information, please see:

• Guidance on registration of clinical trials
• Civil Monetary Penalties Relating to the ClinicalTrials.gov Data Bank https://www.fda.gov/media/113361/download