UAB Policy on ClinicalTrials.gov Registration

Policy

UAB is committed to ensuring compliance with Federal and State law and funding agencies regulations to meet professional publication standards and requirements concerning the public availability of clinical trial data on ClinicalTrials.gov. UAB Researchers have the responsibility to create and maintain records in ClinicalTrials.gov while making determinations about registrations required to comply with ICMJE and CMS. See instructions at the bottom of the policy on who, when, and how to register.

Framework

The Health & Human Services (HHS) regulations mandate registration and results reporting for applicable clinical trials (ACTs) regardless of funding type. ACTs generally include interventional studies of drugs, biological products, or devices that are subject to FDA regulation. (More details at https://clinicaltrials.gov/ct2/manage-recs/fdaaa#WhichTrialsMustBeRegistered.)

The NIH policy mandates registration and results reporting for clinical trials that are funded in whole or in part by NIH, even if they are not ACTs. NIH defines a clinical trial (NIH-CT) as a research study in which one or more human subjects are prospectively assigned to one or more interventions (which include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes. (More details at http://osp.od.nih.gov/office-clinical-research-and-bioethics-policy/clinical-research-policy/clinical-trials.

Effective January 18, 2017, NIH issued its Policy on Dissemination of NIH-Funded Clinical Trial Information.

As part of grant applications or proposals, Principal Investigators 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. See sample below:

Food and Drug Administration Amendments Act (FDAAA) 2007:

1. Trials of Drugs and Biologics: Controlled, clinical investigations, other than Phase I investigations, of a product subject to FDA regulation.
2. Trials of Devices: Controlled trials with health outcomes of a product subject to FDA regulations (other than small feasibility studies) and pediatric post market surveillance studies.
3. Basic Results:
   1. For trials meeting the requirements above, the CT.gov record must also include "basic results" within 12 months from the actual trial primary completion date (the date the final subject was examined or received an intervention for purposes of final collection of data for the primary outcome, whether the clinical trial concluded according to the pre-specified protocol or was terminated).
   2. Delayed submission of results is approved with a valid reason (pending publication is not acceptable reason).

ICMJE Publication

As of 2005, most medical journals including the International Committee of Medical Journal Editors (ICMJE) require a condition of consideration for publication, the prospective registration of certain clinical trials in a public trials registry. Failing to register makes the results of the trial ineligible for publication in ICMJE member journals.

NOTE: Effective July 1, 2008, the ICMJE adopted the World Health Organization (WHO) definition of a "clinical trial"; expanding the current scope of trials which are required to be pre-registered, to include Phase I studies.

Who to Register

The "Responsible Party" is defined as:

1. Commercial sponsor of the clinical trial.
2. Principal Investigator
   1. If so designated by a sponsor, grantee, contractor, or awardee so long as the PI is responsible for conducting the clinical trial and has sufficient data rights (access to and control over the data from the clinical trial, the right to publish the results of the trial, and the ability to meet all of the requirements for submitting information under the law).
   2. If you are the Investigational New Drug (IND) or Investigational Device Exception (IDE) holder, you may be the sponsor as defined in 21 CFR50.3.
   3. If you are a Principal Investigator who has been delegated registration duties by the sponsor.
   4. If you are the funding recipient you may be considered the responsible party. Confirm with your funding agency whether or not you are responsible for registration.

NOTE: NIH grant/progress reports should include a reference to the NCT#.

When to Register

FDAAA 2007

• Trials initiated after 09/27/2007, or trials that are "ongoing" as of 12/26/2007 must be registered in full by: the later of 12/26/2007 or 21 days after the first patient is enrolled.
• Trials that were "ongoing" as of 09/27/2007 and do not involve a "serious or life threatening disease or condition", must be registered by 09/27/2008.
• Trials that were "ongoing" as of 09/27/2007 and do involve a "serious or life threatening disease or condition", and are completed by 12/26/2007 are not subject to the FDAAA requirements.

"Ongoing" in this context means that a trial had one or more subjects enrolled, but had not examined the final subject or provided the final subject an intervention for purposes of final collection of data for the primary outcome as of 09/27/2007.

ICMJE

• Trials that begin on or after July 1, 2005, should be registered before enrollment begins.
• Trials that began enrolling participants before July 1, 2005, were termed "ongoing" trials and were expected to be registered as soon as possible. The ICMJE hoped that all such trials would be registered no later than September 13, 2005.
• Registration must occur before enrolling the first patient.

Penalties for Failure to Register

The FDAAA of 2007 imposes penalties for failure to register or providing false or misleading information. These penalties may include civil monetary penalties and for federally-funded trials, the withholding or recovery of grant funds. Principal Investigators that fail to comply with the requirements may be subject to enforcement actions. Failure to comply with FDAAA requirements may result in financial penalties, withholding of funds and sanctions imposed by the FDA. Failure to comply with NIH may result in withholding of cash payments, disallowing cost for an activity, suspending or terminating either in part or whole the current award, withholding a future award and having a non-compliance notice publically available. Failure to comply with ICMJE requirements may result in an inability to publish in an ICMJE affiliated journal. Failure to comply with CMS requirements can result in a lack of payment for a qualified research billing service and a need to refile the qualified research billing claim. UAB reserves the right to impose discipline or sanctions, up to and including termination, as provided for in applicable university policies.

With regard to ICMJE requirements, researchers who have not registered or have improperly registered their trials take the risk that their manuscripts may not be reviewed and/or accepted to ICMJE members and other medical journals.

How to Register

1. Request creation of a CT.gov user account through UAB's CT.gov administrator.
2. You will receive an email from CT.gov with a login, password, and a link to the PRS (protocol registration system).
3. Access the protocol registration system and create the protocol record per the step-by-step instructions.
   1. Protocol Registration System
   2. Organization: UAB
   3. Username
   4. Password
4. After creating the record, mark the record status as "complete".
5. UAB's CT.gov administrator can review the record to confirm data entry is accurate and complete.
6. CT.gov receives your record and initiates a quality review. Reviewers communicate via email with the "responsible party" regarding any recommended or required changes.
7. CT.gov assigns registry number (NCT#) and notifies the "responsible party" via email.
8. The "responsible party" should review the record for annually. Remember to update the "record verification date" which serves as validation of your review/updates to CT.gov.

NOTE: Even though the "responsible party" is the person with whom CT.gov is communicating, it is only the "owner" (or person who created the record) who can access the record via the protocol registration system.