January 18, 2017: The National Institutes of Health (NIH) policy establishes the expectation that all investigators conducting clinical trials funded in whole or in part by the NIH will ensure that these trials are registered at ClinicalTrials.gov, and that results information of these trials is submitted to ClinicalTrials.gov.
Compliance with Clinicaltrials.gov Requirements
Contact to open a PRS account
January 18, 2017
In 2000, ClinicalTrials.gov was created to establish a registry of clinical trials involving investigational drugs as a result of the Food and Drug Administration Modernization Act of 1997 (FDAMA). Subsequently, the FDA Amendments Act of 2007, Section 801 (FDAAA 801) required additional types of trials to register on the ClinicalTrials.gov website and submit certain data elements. Recently, in September 2016, the Department of Health and Human Services (DHHS) issued a Final Rule clarifying and expanding the registration and results information submission requirements under FDAAA 801. In parallel to the Final Rule, the National Institutes for Health (NIH) issued a complementary policy outlining the requirements for registering and submitting results information to ClinicalTrials.gov. Both the Final Rule and the NIH Policy have effective dates of January 18, 2017, and will impact all new studies and some existing studies at UD Davis Health.
UC Davis Health Compliance issued a research compliance memorandum of the registering and data submission requirements contained in the Final Rule and NIH Policy that impact many of our researchers.
Contact Virina De Jesus at firstname.lastname@example.org to request User Access (and User ID)
Title VIII of the Food and Drug Administration Amendments Act (FDAAA), Public Law 110-85, contains section 402(j), provisions of which require that clinical trials information is to be submitted to the clinical trials data bank, also known as www.ClinicalTrials.gov. This bank is established and maintained by the National Institutes of Health (NIH). The purpose of Title VIII is to provide a means for ensuring that the public has access to information about clinical trials, and provides a mechanism for the public to learn about the results of those trials.
What Studies to Register?
The following new or ongoing clinical trials shall be registered on http://www.clinicaltrials.gov
- Clinical Trials funded either in whole, or in part by National Institutes of Health (NIH).
Definition of a Clinical Trial under the NIH:
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.’’ This definition encompasses phase 1 trials of FDA-regulated drug and biological products, small feasibility studies of FDA-regulated device products, and studies of any intervention not regulated by the FDA, e.g., behavioral interventions.
READ these helpful case studies to determine if your study fits the NIH definition of a clinical trial.
- Trials that meet the clinical trial definition of The International Committee of Medical Journal Editors (ICMJE) that the investigator may wish to publish.
Definiton of a Clinical Trial under ICMJE:
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.
ICMJE journals will consider for publication trials only if registration occurred before the first patient was enrolled ("prospective registration"). http://www.icmje.org/about-icmje/faqsclinical-trials-registration/
- 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.
Definition of a Qualifying Clinical Trial under CMS Clinical Trials Policy:
1. 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).
2. The trial is not designed exclusively to test toxicity or disease pathophysiology and must have therapeutic intent.
3. 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.
At UC Davis Qualifying Clinical Trial Information is collected in the Bridge.
- “Applicable Clinical Trials (ACT)” per FDAAA:
Definiton of Applicable Clinical Trial under FDAAA (see helpful flow chart) :
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:
- 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
The UC Davis Principal Investigator (PI) should consult with commercial sponsors to assure that posting of a trial is in accord with terms of the study contract. A Sponsor providing drug only generally does not accept the registration and results reporting responsibilities. Generally for IND or IDE studies, the responsibility rests with the local investigator.
When Should Studies be Registered?
It is the responsibility of the PI to register the trial in accordance with the following timelines:
ICMJE requires trial registry at or before first patient enrollment as a condition for publication http://www.icmje.org/recommendations/browse/publishing-and-editorial-issues/clinical-trialregistration.html
The Food and Drug Administration Amendments Act (FDAAA) requires that the Responsible Party for an Applicable Clinical Trial must submit required clinical trial information through the Protocol Registration and Reporting System (PRS) no later than 21 days after enrollment of the first participant.
|FDAAA||ICMJE - voluntary||NIH-funded trials||CMS|
|What to register||Applicable Clinical Trials per FDAAA||See definition above||See definition above||Qualifying Clinical Trials|
|When to register||At trial initiation (no later than 21 days of enrollment of the first subject); update at least every 12 months||Prior to first subject enrollment||Same as FDAAA||Before claims are submitted to Medicare|
|Results Reporting||No later than 12 months after the Primary Completion Date (the last subject last visit||Not required||Same as FDAA||Not required|
|If non-compliant||Public notice; FDA sanctions, civil monetary penalties (up to $10,000/day)||Rejection of the publication||NIH funds withheld for the PI and the Institution||Denial of claims|
The Centers for Medicare and Medicaid Services (CMS) issued a Transmittal requiring new mandatory reporting of the clinicaltrials.gov clinical trial number (also known as NCT#) on all hospital and professional claims for related items/services. Effective January 1, 2014, it will be mandatory to report the clinical trial number on claims for items/services provided in all clinical trials that are qualified for coverage.
In order for the NCT# to correctly appear on the claims, the study teams need to type the number in the corresponding field of the BRIDGE.
ClinicalTrials.gov Protocol Registry System Instructions, Specific to University of California, Davis.
1. It is the study Sponsor’s responsibility to register the trial with ClinicalTrials.gov.
- If you wrote the study protocol (Sponsor Investigator-Initiated, you are considered the study Sponsor
- If the study protocol was sent to you by an industry sponsor, then the industry sponsor will have the responsibility to register the trial.
- If industry is supplying a drug or device for your study, but you are the author of the study, then it is your responsibility to register your trial.
- If you have received grant funding to conduct a clinical trial then you, as the awardee, are considered the Sponsor for that trial.
2. In order to establish user access, you must have a UC Davis email address and a UC Davis telephone extension.
3. In order to register your clinical trial with ClinicalTrials.gov you will need to request User access. Please contact the UC Davis ClinicalTrials.gov Administrator, Virina De Jesus, Sr. CRC, CTSC, to get your account established. You will be assigned a User ID. UC Davis has an established Organization Account for all UC Davis investigators to register under. DO NOT request an Individual Account or another Organizational Account on the clinicaltrial.gov website.
4. Once you are assigned a User ID, you will receive an email from ClinicalTrials.gov with your temporary password. Click on the link in the email to get to the ClinicalTrials.gov Protocol Registry System Log-In page: https://register.clinicaltrials.gov/
5. Login Page:
- Organization: UCaliforniaDavis (NO SPACES-Case Sensitive)
- User Name: as it was assigned to you in your notice from PRS
- Password: enter your temporary password
1) Under the “User Account” section, click on “Change Password". Please change your temporary password to one that you will be able to remember.
2) Read the Quick Start Guide in the “Help” section. For additional help, there is also a User’s Guide and Data Element Definitions which explains each type of entry.
3) Unique Protocol ID: MUST use the IRB number assigned to this protocol (e.g., 123456). You don’t need to put the numerical suffix on this number. DO NOT enter a new listing for each renewal year.
4). ClinicalTrials.gov ID: Leave this blank – It will be assigned by ClinicalTrials.gov once the listing is approved in the registry. (usually takes 2 – 5 working days)
5). FDA Regulated Intervention: If subjects are being given any drug (investigational or already approved) this answer is YES. If the study involves an investigational Device this answer is YES. If the study involves any Biologicals or vaccines, this answer is YES.
6). Secondary ID: this can be a grant number or some other study number that is frequently referred to for this protocol. DO NOT enter IRB number with numerical suffixes.
7). Section 801 Clinical Trial: Does this trial qualify as an “Applicable Clinical Trial” under the regulations? (See Data Element Definitions in Help menu: #2 US FDA Info.)
8). Responsible Party: This will be Sponsor, Principal Investigator or Sponsor-Investigator.
|Sponsor:||Only entered by study Sponsor or in some cases for consortium trials|
|Principal Investigator:||Need to include PI Name, Official Title, & Affiliation Institution|
|Sponsor-Investigator:||Fields will automatically populate with PI Name & UCaliforniaDavis|
|For Existing Studies||When you enter ClinicalTrials.gov to update an existing entry, you will see a WARNING message stating: “Responsible Party has not been entered.” Below this will also be an “NOTE” stating: “Responsible Party was entered in the old format as: John Doe, MD, University of California, Davis.” You need to change the definitions as described above. The old Responsible Party data elements will continue to show in the listing until you enter information in the new format. Your study will not be affected.|
IMPORTANT: Previously, the UC Davis Clinicaltrials.gov Administrator, was able to approve and release the registry listing and updates to ClinicalTrials.gov. Under the new process, the Investigator must Approve and Release the record for QA review and processing by ClinicalTrials.gov. The investigator does this by selecting:
Next Action: Approve [click Approve], and then, Next Action: Release [click Release]
The investigator must be listed on the pull-down Access List on the same screen. The pull-down includes the list of all user names within the current ClinicalTrials.gov PRS organization. The investigator name must be selected from this pull-down list. If the name is not listed, the investigator must establish access as a “User” by contacting the UC Davis PRS Administrator.
9). Review Board:
|Board Name:||UC Davis Institutional Review Board|
|Board Affiliation:||University of California, Davis
|Business Address:||IRB Administration
University of California, Davis
2921 Stockton Blvd., CTSC Bldg.
Sacramento, CA 95817
|United States:||Institutional Review Board|
|AND (for drug studies) United States:||Food and Drug Administration|
10). Record Verification Date: This is the date you enter information into this listing. ANY TIME you change information in this listing, or go in to check it, CHANGE THIS DATE TO THE CURRENT MONTH YEAR. YOU ARE REQUIRED TO REVIEW THE LISTING AT LEAST EVERY 6 MONTHS.
11). Study Start Date: Month Year first enrolling study subjects
12). Study Primary Completion Date: Month Year last study subject data is collected for the Primary Outcome Measure
13). Study Completion Date: Month Year last study subject data is collected for all Outcome Measures.
14). Accepts Healthy Volunteers? If the eligibility criteria require subjects to have some type of medical condition then this answer is NO. If subjects may be enrolled who DO NOT have any medical conditions, but will be given the investigational intervention as a study CONTROL subject, then the answer is YES.
15). Study Official: This should be the PI
16). Location: Where the study will take place. You must list a contact name/phone with this. You will also be asked what the recruiting status is at this location.
Basic Results are required to be entered into the registry within 12 months of the Primary Completion Date.
Some DO’s and DON’Ts
DON'T enter a study twice. DON'T enter a study each time the IRB renewal goes through –it’s the same study – if there are amendments/modifications and it changes the information in the listing, then DO go in and change the info in the listing using edit buttons. (and remember to change the Record Verification Date again!!).
DO look at the Record Log section for notes/information regarding the listing. Sometimes these come from the Protocol Registration System Quality Control/Quality Assurance group. DO call or email if you have a question. Questions? Contact Virina De Jesus, Clinical Research Supervisor, CTO, 916-703-9174; email@example.com
Clinicaltrials.gov provide a step-by-step details on how to submit Resuts. This website also contains training presentations and tempaltes https://clinicaltrials.gov/ct2/manage-recs/how-report
Four types of data need to be included in Results Reporting:
- Participant Flow. A tabular summary of the progress of participants through each stage of a study, by study arm or comparison group. It includes the numbers of participants who started, completed, and dropped out of each period of the study based on the sequence in which interventions were assigned. Essentially a tabular adaptation of "Figure1" format from a publication.
- Baseline Characteristics. A tabular summary of the data collected at the beginning of a study for all participants, by study arm or comparison group. These data include demographics, such as age and gender (minimal requirements). Other desired elements are: region of enrollment, and study-specific clinical measures (for example, systolic blood pressure, prior antidepressant treatment). Informative Titles are required for Arms/Groups, and description of Arm/Group should contain information about the intervention administered.
- Outcome Measures and Statistical Analyses. A tabular summary of outcome measure values, by study arm or comparison group. It includes tables for each prespecified Primary Outcome and Secondary Outcome and may also include other prespecified outcomes, post hoc outcomes, and any appropriate statistical analyses.
- Adverse Events. A tabular summary of all anticipated and unanticipated serious adverse events and a tabular summary of anticipated and unanticipated other adverse events exceeding a specific frequency threshold. For each serious or other adverse event, the summary includes the adverse event term, affected organ system, number of participants at risk, and number of participants affected, by study arm or comparison group.
For clinical trials initiated on or after January 18, 2017:
- Clinical trial information submitted to ClinicalTrials.gov must be updated not less than once every 12 months.
- Some data elements be updated more rapidly, as summarized in in this attachment.
- If a protocol is amended in such a manner that changes are communicated to human subjects in the clinical trial, updates to any relevant clinical trial information must be submitted not later than 30 calendar days after the protocol amendment is approved by an IRB.