Clinical Trials Registration

It is the policy of the University of South Carolina that clinical trials are registered in a manner that is consistent with federal agency requirements. Specifically, trials must be registered in a database called ClinicalTrials.gov when they begin. The record must be updated throughout the study with results provided when the study ends. Significant penalties can be applied by the agencies if these requirements are not met – including loss of an investigator’s ongoing or pending grant funding.

Definition of a Clinical Trial

The U.S. National Institutes of Health (NIH) defines a clinical trial as: "A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.”

Click here to evaluate whether your NIH-funded study meets the NIH definition of a clinical trial

The FDA defines an Applicable Clinical Trial (ACT) as follows:

Trials of drugs and biologics: controlled clinical investigations, other than Phase 1 investigations, of a product subject to FDA regulation.
Trials of biomedical devices: 1) controlled trials with health outcomes of devices subject to FDA regulation, other than small feasibility studies, and 2) pediatric post-market surveillance.
Click here to evaluate whether your study is an Applicable Clinical Trial (ACT) under 42 CFR 11.22(b)

The International Committee of Medical Journal Editors (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 cause-and-effect 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. Health outcomes are any biomedical or health-related measures obtained in patients or participants, including pharmacokinetic measures and adverse events.”

When to Register and Report

	ICMJE	FDAAA and HHS RULE	NIH
When to Register the Trial	Prior to enrollment of first subject	Within 21 days of enrollment of first subject	Within 21 days of enrollment of first subject
When to Report Results	Not applicable	Within 12 months of final data collection for primary outcome	Within 12 months of final data collection for primary outcome

PI Responsibilities

The PI can delegate the responsibility for entering the information required for registration, updates, and results reporting – but the PI remains responsible for:

The accuracy and completeness of the information
The Approve and Release actions that are required each time information is entered into the trial record
Obtaining an account with the PRS data entry system used by ClinicalTrials.gov, so that s/he can log into the system for the Approval and Release actions

An extensive amount of detailed information is required. The time and knowledge necessary to create a record (register) and to enter results should not be under-estimated

Consent Form Requirements

Regulations require a statement in the consent form(s), without revision. The required language is already included in the USC informed consent form template.

Consequences and Penalties

Federal agency penalties for non-compliance were generally not enforced prior to January 18, 2017. However, the expanded requirements implemented on this date include additional possible penalties and a declaration of intent to enforce the penalties. The range of possible agency actions is summarized below.

FDA-regulated research

Civil monetary penalties for the responsible party of $10,000 (initial) and $10,000/day for duration of the uncorrected non-compliance
Public notice of non-compliance at ClinicalTrials.gov
HHS agencies (e.g., NIH) may withhold continuing funds for existing grants, and/or awards of new funding to the PI
HHS research funding to the entire institution could be withheld

NIH-sponsored research

Public notice of noncompliance at ClinicalTrials.gov
HHS agencies (e.g., NIH) may withhold continuing funds for existing grants and/or awards of new funding to the PI
HHS research funding to the entire institution could be withheld

Medicare
Claims will not be paid

International Committee of Medical Journal Editors
Inability to publish in prominent medical journals

Office of Research Compliance
USC IRB approval will not be renewed unless a trial has been registered

These requirements have existed for many years for most FDA-regulated trials but were significantly expanded as of January 18, 2017.
The revised requirements now also apply to trials funded by NIH, whether or not they are FDA-regulated.
The revised regulations also include expanded penalties for noncompliance, together with a statement that federal agencies will begin using the penalties to enforce compliance.
In addition, many scientific journals have stated that they will not publish clinical trials that have not registered at ClinicalTrials.gov.

Office of Research Compliance