Clinical Trials & Related Requirements

Clinical trials must be placed in a public database, ClinicalTrials.gov, as mandated by federal agencies. The trials are required to be registered when they begin and updated throughout the life of the study. Additionally, study results must be provided upon completion of the study. Monetary penalties can be applied by the agencies if the requirements are not met.

The revised requirements to register applicable clinical trials now also apply to trials funded by NIH, whether they or not they are FDA-regulated. The expanded regulations also include increased penalties for noncompliance. Furthermore, several scientific journals have specified they will not publish clinical trials which have not registered.

Clinical trials funded by in whole, or in part, by National Institute of Health

Definition of Clinical Trial as determined by the NIH:

A research study in which one or more human subjects are prospectively assigned to one or more interventions to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.”

This definition encompasses phase 1 trials of FDA-regulated drug and biological products, small feasibility studies of FDA-regulated device products, and study of any intervention not regulated by the FDA, (i.e., behavioral interventions)

Trials that meet the clinical trial definition of the International Committee of Medical Journal Editors (ICMJE) that the investigator may publish.

Definition as determined by ICJME:

Any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes. Health-related interventions include any intervention used to modify a biomedical or health-related outcome (for example, drugs, surgical procedures, devices, behavioral treatments, dietary interventions, and process-of-care changes). Health outcomes include any biomedical or health-related measures obtained in patients or participants, including pharmacokinetic measures and adverse events. Purely observational studies (those in which the assignment of the medical intervention is not at the discretion of the investigator) will not require registration. NOTE: Registration must occur before the first patient was enrolled.

Qualifying clinical trials that will render claims for items/services to the Center for Medicare and Medicaid Services.

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.

Definition of a Qualifying Clinical Trial under CMS Clinical Trials Policy:

The subject or purpose of the trial is the evaluation of an item or service that falls within a Medicare benefit category (e.g., physicians’ service, durable medical equipment, diagnostic test) and is not statutorily excluded from coverage (e.g., cosmetic surgery, hearing aids).
The trial is not designed exclusively to test toxicity or disease pathophysiology and must have therapeutic intent.
Trials of therapeutic interventions must enroll patients with diagnosed disease rather than healthy volunteers, although trials of diagnostic interventions may enroll healthy patients to have a proper control group.

Applicable Clinical Trials per FDAAA:

Trials of Drugs/Biologics: Controlled, clinical investigations of a product subject to FDA regulations, other than Phase I. This may include interventional studies with dietary supplements.

Trials of Devices: Prospective controlled trials with health outcomes, which compares an intervention with a device against a control, other than small feasibility studies. Includes Pediatric post-market surveillance studies.

Applicable Clinical Trials under FDAAA also meet one of the following conditions:

Checklist for Evaluating whether a Clinical Trial or Study is an Applicable Clinical Trial

• 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

FDAAA requirements for registration exclude the following (unless funded either in whole, or in part by NIH):

• (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

Click below to open a PDF for our IPD Tool on Understanding Data Sharing Statements

The responsible party is considered to the study sponsor (i.e, IND or IDE holder or the initiator of the study) or a sponsor-designated PI who is responsible for conducting the study, and has access to and control over the clinical data to analyze the data and publish the results.

The PI should consult with industry sponsor to assure that posting of a trial is in accordance with terms of the study contract. A sponsor whom provides study drug only typically does not accept the registration/results reporting responsibilities.

ClinicalTrials.gov Registration Guide

• Initial Registration: No later than 21 days after enrollment of first subject
• Interim updates: The record must be updated annually (even if nothing has changed) until the final results are reported. NOTE: Specific type of changes must be reported within 30 days.
• Reporting Results: No later than one year after the trial’s primary completion date. This is the date when the final subject was examined or received an intervention for the purposes of collection of data for primary outcomes.

Specific information on the data elements required by FDA and NIH for registration reporting is located on the ClinicalTrials.gov Protocol Registration System information website.

Data elements for protocol registration
Data elements for results reporting

The PI can delegate the responsibility for entering information for purposes of registration, updates and reporting of results, however, the PI remains responsible for:

• The accuracy of the information
• The Approve and Release actions which are required every time information is entered into the record

Federal regulations require that consent forms included the following statement, without revision. This is included in the standard consent template:

A description of this clinical trial will be available on http://www.ClinicalTrials.gov as required by U.S. Law. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time.

Failure to register, or provide incomplete/false information (including updates subsequent to initial registration) may include monetary penalties of up to $10,000 per incident and/or per day, non-compliance notification from the FDA, and for federal sponsored studies, the withholding or recovery of grant funding.

NIH grantees are required to certify compliance with registration/reporting requirements in grant applications and progress reports.

Suggested Best Practices for ClinicalTrials.gov Activity during the COVID-19 Pandemic

Food and Drug Administration

• Checklist for Evaluating whether a Clinical Trial or Study is an Applicable Clinical Trial
• Summary of Changes effective January 18, 2017

Clinical Trials.gov

• www.ClinicalTrials.gov
• ClinicalTrials.gov FAQs
• Clinical Trials.gov Protocol Registration System
• Results Reporting – Checklists, Templates, and Examples
• Training Material
• Protocol Registration and Results System (PRS) Guided Tutorials

National Institutes of Health

• FAQs for NIH Grantees
• NIH Implementation of FDAAA
• NIH Protocol Template for Behavioral and Social Sciences Research Involving Humans