Register Clinical Trials at ClinicalTrials.gov
Frequently Asked Questions About the FDA / NIH / ICMJE Requirements
What is the requirement?
Over the past ten years, government agencies and the International Committee of Medical Journal Editors have issued laws and directives on the subject of trial registration. All
parties have consistently agreed that the purpose of trial registration is to promote the public good by ensuring that the existence and design of clinically directive trials are
publicly available. The registration effort began with the development of a publicly available Web site, ClinicalTrials.gov. ClinicalTrials.gov is a service of the NIH, developed by the
National Library of Medicine.
In 1997, the FDA/NIH began requiring registration for only a limited number of trials, Then, in September, 2007, the Food and Drug Amendments Act (Title VIII. Sec. 801) significantly
expanded the scope of clinical trials that must be registered and set civil monetary penalties for failing to register “applicable trials.”
In 2004, the International Committee of Medical Journal Editors (ICMJE) defined trials that must be registered in order to be considered for publication in journals that adhere to
ICMJE standards. In 2007 the ICMJE expanded the definition of trials that must be registered. Scores of journals (not limited to medical journals) have adopted the registration policy.
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For registration purposes, how is “clinical trial” defined and what are the registration deadlines?
According to the International Committee of Medical Journal Editors (ICMJE):
2005 definition statement: “Any research project that prospectively assigns human subjects to intervention and comparison
groups to study the cause-and-effect relationship between a medical intervention and a health outcome. The trial must have at least one prospectively assigned concurrent control or
comparison group in order to trigger the requirement for registration.” This definition specifically excluded Phase I trials.
2007 definition statement: “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.” This definition includes Phase I trials.
Deadlines for registration: Currently, the ICMJE follows its 2005 definition. The ICMJE will start to implement the expanded (2007) definition for all trials that begin
enrollment on or after July 1, 2008. The ICMJE will not strictly impose this expanded definition until the stated date. However, trials that meet the expanded definition CAN be
registered before the stated date, and the ICMJE encourages investigators to do so, noting that such action is consistent with their goal of “full transparency" with respect to
performance and reporting of clinical trials.
According to the FDA and the NIH:
1997 Definition: The Food and Drug Modernization Act, later clarified by FDA guidance documents, required sponsors to register clinical trials conducted under an
investigational new drug application (IND) for drugs or biological agents intended to treat a serious or life-threatening disease or condition and intended to test effectiveness.
2007 Definition: The Food and Drug Amendments Act (Title VIII. Sec. 801) requires registration for all “applicable clinical trials,” including Federal, industry-sponsored, and
investigator-initiated that are:
1) Trials of drugs and biologics: Controlled, clinical investigations, other than Phase I investigations, of a product subject to FDA regulation, and
2) Trials of devices: Prospective clinical studies of health outcomes comparing an intervention with a device against a control in human subjects (other than small clinical trials to
determine the feasibility of a device, or clinical trials to test prototype devices where the primary outcome measure relates to feasibility and not to health outcomes); and pediatric
postmarket surveillance studies, as required under the Federal Food, Drug and Cosmetic Act.
Deadlines for registration: This Food and Drug Amendments Act of 2007 requires that all trials, regardless of sponsor, initiated after September 27, 2007 or ongoing as of December 26,
2007 must be
registered in full by the later of December 26, 2007 or 21 days after the first patient is enrolled. All trials that were ongoing as of September 27, 2007 and do not involve serious or life-threatening
conditions must be registered by September 27, 2008.
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What are the penalties for failing to register?
According to the ICMJE:
Unregistered trials will not be considered for publication in journals that adhere to ICMJE standards. This penalty has not changed over time.
According to the FDA/NIH (Food and Drug Amendments Act of 2007):
Penalties may include civil monetary penalties up to $10,000 fine for failing to submit or for submitting fraudulent information to ClinicalTrials.gov. After notification of
noncompliance, the fine may go up to $10,000 per day until resolved. For federally funded grants, penalties may include the withholding or recovery of grant funds.
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Who is responsible for registering a trial?
Normally, the clinical trial will be registered by the sponsor.
- NIH-sponsored trials should normally be registered by the Institute that is funding the research
- Industry-sponsored trials (industry-written protocol) should normally be registered by the industry sponsor.
- Multi-site trials should be coordinated among the sites and registered by the “lead sponsor” so that ClinicalTrials.gov does not receive multiple registrations for the same trial.
However, some trials will need to be registered by the PI:
- Investigator-initiated trials (for which industry has supplied drug or grant funds) should normally be registered by the PI.
- Trials for which PIs hold their own INDs or IDEs should normally be registered by the PI. (PIs who hold their own INDs or IDEs are considered to be the trial sponsors.)
- Trials that the sponsor has declined to register.
The PI is ultimately responsible for determining that registration requirements are met. Although some sponsors will do the actual registration work, it is still the PI’s
responsibility to ensure that the registration has been accomplished. Before enrolling subjects, every PI should ask the study’s sponsor, “Is this study fully registered?” If the sponsor
responds affirmatively, PIs should personally check ClinicalTrials.gov to ensure that the trial has been registered.
For registration instructions at the UConn Health Center, see below “How do PIs register their trials?”
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The terms "health-related interventions" and "health outcomes" suggest that this requirement applies only to biomedical clinical trials. Is that correct?
No. According to the ICMJE, “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.
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Are there any exceptions?
Yes. Purely observational studies (those in which the assignment of the medical intervention is not at the discretion of the investigator) do not require registration.
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What if I am uncertain about whether to register my trial?
According to the ICMJE:
Those who are uncertain whether their trial meets the ICMJE definition should err on the side of registration if they wish to seek publication in an ICMJE journal.
According to the FDA and the NIH:
Both agencies encourage the registration of ALL trials, whether or not required under the FDA Amendments Act of 2007.
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Where / what are the registries?
Over time, ClinicalTrials.gov has become the registry of choice and is now the registry required by the FDA Amendments Act of 2007.
ClinicalTrials.gov is a service of the NIH, developed by the National Library of Medicine.
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How is the UConn Health Center involved?
The UConn Health Center is already registered as an institution at ClinicalTrials.gov, and UConn Health Center-based trials have already been registered at this site. In addition, ClinicalTrials.gov
asks each institution to identify a Protocol Registration System (PRS) administrator. At the UConn Health Center, the PRS Administrator is Judie Fine in the Office of Clinical and
Translational Research, School of Medicine.
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How do PIs register their trials?
If after reading this information, you determine that you need to register your clinical trial at ClinicalTrials.gov, call your trial's sponsor/program officer. Ask whether the trial
has already been registered and/or whether the sponsor intends to register the trial.
- If the answer is "no" to both questions, proceed to step 1, below.
- If the sponsor states that the trial has already been registered, check the information about your trial on ClinicalTrials.gov., e.g., for multi-site studies, be sure that your
site is listed and that the information is accurate.
- If the sponsor intends to register the trial, be sure that registration occurs before you enroll your first subject. Once the trial has been registered, check the record for
accuracy.
To register your trial:
1. Send an email message to: fine@nso.uchc.edu
2. Include in the message your name, telephone number, and email address and state you would like to be a registered "user".
3. Receive by return email a login name and a temporary password. Save your password; you will need it for periodic updates and verification.
4. Go to the Clinicaltrials.gov Registration Web site.
5. Complete the login fields. In the “Organization” field, state “UCHC”
6. Browse the Main Menu page. Under “User Account,” follow the instructions for changing your temporary password as soon as possible. Under "Help", refer to the “User’s Guide” for
additional information. As the PI, you are a “user,” (also known as “owner”) and you are responsible for entering the information about your trial, ensuring that the information is
correct, and updating the information in a timely manner (for updating, see NOTE at the end of this section).
7. On the Main Menu page, under "Protocol Record" click on “Create” and complete the study description template. Note that the ClinicalTrials.gov required fields are marked with a red
asterisk (*). These data elements represent the requirements for an adequate registration. Complete the following (potentially confusing) fields as follows:
- Organization’s Unique Protocol ID: Use the IRB number.
- Oversight Authorities: If this is not an FDA-regulated protocol, state “United States: IRB”
- Sponsor: The database will default to “University of Connecticut”, even through you may have entered University of Connecticut Health Center.
- Collaborators: Sponsorship can be clarified by entering the actual sponsor’s name as an “agency.” For example, if this is an investigator-initiated clinical trial and you (the PI)
hold the IND/IDE, list yourself.
- Record Verification Date: Enter the month and year in which you complete and submit the template to the PRS Administrator.
- Last Follow-Up Date: When creating the template, specify the anticipated last follow-up date.
- Conditions: Use the MeSH controlled vocabulary. If you don’t, ClinicalTrials.gov staff is likely to delete your term and choose one of their own.
- Keywords: Use the MeSH controlled vocabulary. If you don’t, ClinicalTrials.gov staff is likely to delete your term and choose one of their own.
ClinicalTrials.gov data element definitions are available at http://prsinfo.clinicaltrials.gov/definitions.html.
8. If the PI did not personally complete the template, send the draft template to him/her for review and approval. Note: This is an important step. The UConn Health Center Office of
Clinical and Translational Research requires PI sign-off on a printed copy of the completed template prior to submission to ClinicalTrials.gov.
9. Submit the completed, PI-approved, template by clicking on "Complete". The completed template will go electronically to the UConn Health Center PRS Administrator. Send a paper copy
of the latest IRB approval (initial or continuation) to Judie Fine, PRS Administrator (MC 3955) for submission to ClinicalTrials.gov. The Administrator will then release the template to
ClinicalTrials.gov.
NOTE: The PI is responsible for periodic updates to the study record, e.g., changes in recruitment status, protocol revisions, change in contact information, etc. The
PI is also responsible for verifying the study record at least once every six months while the study is open (even if there have been no changes) and annually after the study has closed.
For active studies at the UConn Health Center, the UConn Health Center PRS administrator will notify the PI at 5 months that the protocol record is due to be updated in the next 30 days.
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Does the registration posting need review by the IRB?
No. The UConn Health Center PRS Administrator will require proof of IRB approval for each study in order to submit that documentation to ClinicalTrials.gov, but the UConn Health
Center IRB will not review the postings.
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Is more information available?
Yes.
For more information about the ICMJE registration requirement, see:
For more information abut the FDA Amendments Act of 2007, see:
PRS and U.S. Public Law 110-85 [back to top]
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