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Complying with ClinicalTrials.gov at IU
ClinicalTrials.gov, commonly known as CT.gov, is a web-based resource that provides the public with information on privately and publicly funded clinical trials. The website, maintained by the National Library of Medicine (NLM) at the National Institutes of Health (NIH), is made up of unique clinical trial “records” that are further comprised of two major components: trial registration information and trial results.
- Registration modules include elements such as a basic overview of the study’s design, a listing of the study’s outcomes, the desired subject population, participating site locations, and information about the study’s progress.
- The trial results modules, when required, include information about trial participants and their baseline characteristics, outcome measure values and any appropriate statistical analysis, as well as a summary of adverse events.
Registration and results reporting on CT.gov may be required, either under federal law or as a condition of funding, or may be pursued voluntarily by the trial’s sponsor or lead Principal Investigator (PI). The entity or individual who is accountable for the record’s creation and maintenance is the Responsible Party. This might be the industry sponsor, the prime awardee of the funding, or an individual investigator. When Indiana University is serving as the sponsor or is the prime awardee, IU designates the IU PI to be the Responsible Party.
While IU PIs are ultimately responsible for ensuring the compliance of IU records, Indiana University's ClinicalTrials.gov compliance program assists the research community with determining applicable requirements for registration and results reporting, navigating the CT.gov system, maintaining IU records in good standing, and keeping up to date on regulatory changes and updates. IU's CT.gov compliance program also conducts periodic monitoring and auditing of selected records to verify the record’s accuracy and to alert investigators of problems that should be addressed or upcoming CT.gov related deadlines.
In addition to the information provided below, general information regarding CT.gov definitions, requirements, and processes can be found on the ClinicalTrials.gov FAQ page. Information regarding IU requirements for registration and results reporting can be found in the IU HRPP Policy on ClinicalTrials.gov Compliance.
Studies Requiring Registration and Results Reporting
A clinical trial must be registered on CT.gov if it meets one or more of the following criteria:
- A Food and Drug Administration (FDA) regulated applicable clinical trial (ACT)
- NIH-funded clinical trial
- Plan to publish in an International Committee of Medical Journal Editors (ICMJE) member journal
- Qualifying clinical trials which involve billable services under Centers for Medicare and Medicaid Services (CMS) requirements
For trials requiring registration under FDA regulations or NIH policy, trial results must also be posted on CT.gov.
At IU, studies meeting either the FDA or NIH requirements are considered mandatory registrations. Studies registered to comply with ICMJE requirements or CMS billing requirements, and studies registered for any other non-mandatory reason, are considered voluntary registrations.
For both mandatory and voluntary registrations, the Responsible Party (IU PI) must ensure that the registration is successfully completed, resulting in the generation of the National Clinical Trial number (NCT number), and that the record is accurately maintained throughout the study’s lifespan, including the submission and posting of results information when required.
Each trial, including multi-center studies, should only be registered on CT.gov once. For multi-center studies, the Responsible Party is often the sponsor or the prime awardee of the funding. IU PIs should generally only serve as the Responsible Party for those studies in which they serve as the sponsor-investigator or the lead PI.
CT.gov records are created and edited within CT.gov's Protocol Registration and Results System (PRS). Each organization, such as a company, university, or medical center, has an organizational PRS account which provides their users with access to the clinical trial records for which they are responsible. Access to the IU PRS is managed by the IU ClinicalTrials.gov compliance program.
- To request a new user account, send an email to email@example.com and include the following information: the new user's name, contact information (email and phone number), official title of the new user, and the preferred PRS username (most use their IU username).
- If your current account is no longer accessible or requires modifications, send an email to firstname.lastname@example.org and include the following: account holder name and a description of the modification/issue.
The person who creates the study record in CT.gov becomes the record owner. This individual may be someone other than the Responsible Party/IU PI and is often the trial’s primary coordinator or a departmental regulatory coordinator. All email communications from the national PRS portal will be sent to both the Responsible Party and the record owner.
The record owner may maintain the record themselves or may grant additional users access to make record changes. Upon log-in, an IU user will only have access to those records for which they are the record owner or for which the record owner has granted them access.
A record owner on an existing ClinicalTrials.gov record may need to be modified due to personnel or responsibility changes. To request modifications to an existing record owner, send an email to email@example.com and include the following information: National Clinical Trial Number; Institutional Review Board (IRB) protocol number; full name of new record owner; and account information if the user is new. To expedite such requests, the current record owner, the new record owner, and the principal investigator/responsible party should be copied on this request.
When a record is created or modified in any way, several steps must be taken to submit the content to the national PRS portal managed by staff employed by NLM.
ENTRY COMPLETE – When the individual modifying the record is done entering data or making edits to the content, they must take the Entry Complete action. This action prepares the record content for review by the Responsible Party. If the need to make additional edits is discovered, the record can be reset to an in-progress status at any time prior to the final release of the revisions.
APPROVE – Once the Entry Complete action has been taken, the Responsible Party must review the content for accuracy to ensure that no additional modifications are required. Following the content review, the Responsible Party must take the Approve action. The PRS system will only allow the Responsible Party to take the Approve action.
RELEASE – Once the record is Approved, the Responsible Party must take an additional action to release the content out of the IU PRS portal for review by NLM. Only the Responsible Party can take the Release action. When the Release action is initiated, the Responsible Party is asked to attest to their identity and to the accuracy of the record’s content. When the Release action is completed, the new content is forwarded to the NLM team to initiate their quality assurance (QA) review process. The record status will then appear as “Under PRS Review.”
Once received, the NLM team will initiate QA and may return the submission to the Responsible Party with requests for modification, termed PRS Review Comments. Additional information regarding Review Comments is included in the Study Registration and Results Reporting sections below.
During the QA process, no additional changes can be made to the record without withdrawing the previous submission. If the submission is withdrawn, the PRS review will not be re-initiated until the Entry Complete, Approve, and Release Statuses are repeated. If a record owner or staff other than the Responsible Party revises a record, they are responsible to ensure the Responsible Party completes the Approve and Release actions.
Clinical Trials.gov registration, record maintenance, problem resolution
The FDA, NIH, and ICMJE define when trial registration information must be submitted:
- FDA and NIH require the registration to be submitted no later than 21 days after the first subject provides consent for participation.
- ICMJE requires the registration to be submitted prior to the first subject providing consent for participation.
Specific data elements, such as study design, outcome measures, eligibility criteria, as well as information about the study’s reviewing IRB and Data Monitoring Committee (if applicable), are required in the PRS system to register a study. Resources, including instructions and reference materials related to the study registration process, are available on the PRS website.
Once a study registration record has been completed by the user and approved and released by the Responsible Party, it must then be reviewed by NLM staff before the study record will be published to the public CT.gov site. The National Clinical Trial (NCT) number will not be issued until this occurs.
NLM QA review generally takes between two and five business days. If NLM staff have issues with the content, the registration may be returned to the record owner and responsible party with PRS Review Comments. PRS requires Major Review Comments generated during QA review to be addressed within 15 calendar days. Upon request, IU CT.gov compliance program staff can assist study teams in responding to these comments and/or contacting PRS for additional guidance.
Until the registration content passes the NLM QA review, the public trial registration listing will not be created or updated. For new registrations, the NCT number is issued upon the NLM team’s acceptance of the content, at which point, the record will be transferred to the public website. Until an NCT number is issued, the trial has not been successfully registered on CT.gov.
If a duplicate trial registration is created in error, the IU CT.gov compliance staff can delete the record prior to it being submitted to the NLM team for QA review. If the trial has been granted an NCT#, the record cannot be deleted, but we can request the record’s suppression from the public website as a duplicate record.
All active study records on CT.gov mut be verified for accuracy at least once every 12 months. To complete this process, the verification date in the ClinicalTrials.gov record needs to be modified and re-submitted to the national PRS team at least every 12 months, even if no other changes to the record are made. To prevent a lapse in this requirement, it is advised that this date be updated every time the ClinicalTrials.gov record is modified.
For FDA-regulated studies registered on CT.gov (regardless of whether the registration is mandatory or voluntary), federal regulations require specific updates to be made during the life of the trial.
Responsible Parties must
- Update ClinicalTrials.gov record within 15 days following a change to:
- Device approval status (if the device under investigation was not approved or cleared by the Food and Drug Administration at the time of study registration, but undergoes a change in approval or clearance status
- Update ClinicalTrials.gov record within 30 days following a change to:
- Study start date (after the first subject is consented)
- Intervention name (if a non-proprietary name is established for any intervention included in the record)
- Availability of expanded access (only required when the responsible party is both the manufacturer of the investigational drug product and the trial sponsor)
- Overall recruitment status
- Individual site status
- IRB approval status
- Primary completion date (after the trial reaches the actual primary completion date)
- Study completion date (after the trial reaches the actual study completion date)
- Responsible party and contact information
- Changes made via protocol amendment that impact any registration data elements on CT.gov if such changes are to be communicated to human subjects (following IRB approval of the amendment)
- Any content changes including modification needed to the posted protocol and/or statistical analysis plan
For non-FDA regulated trials, compliance with the FDA deadlines is not required, but is strongly recommended to ensure that the record remains accurate throughout the trial’s lifespan.
Detailed instructions available on the PRS website can assist you with record maintenance.
If the PI listed as the Responsible Party on a CT.gov record leaves IU, is no longer involved with the clinical trial, becomes incapacitated, or dies, the affected CT.gov record must be modified. The following tasks should be completed 30 days prior to any change in PI. If the change in PI is unexpected, the following tasks should be completed as soon as feasibly possible following the PI departure:
- Notify the IU CT.gov compliance staff by emailing firstname.lastname@example.org to inform them of the PI change.
- If the trial will remain active at IU (data collection will continue) but the departing PI will continue the study at their new institution and the departing PI will act as lead PI for both sites, seek guidance from the IU CT.gov compliance staff regarding whether the record may be transferred to the departing PI’s new institution. Note that record transfers may only be initiated by IU CT.gov compliance staff.
- If the trial will remain active at IU (data collection will continue) and the departing PI will not continue the study at their new institution, complete the modification in CT.gov to change the PI/Responsible Party.
- If the trial is not continuing (data collection will not continue), mark the record as completed/terminated/withdrawn ensuring that any other necessary record updates are also completed at the same time.
- Note that results reporting will still be required for a completed/terminated/withdrawn study if it otherwise met results for mandatory registration and results reporting.
- If results reporting is required and cannot be completed at the time the record is marked as completed/terminated/withdrawn, the Responsible Party should still be updated to list the new PI or the person who will be responsible for results reporting. Contact IU CT.gov compliance staff for guidance in these situations.
Providing research results in the CT.gov record is required for mandatory registrations (those subject to FDA or NIH registration requirements). The timeline for results submission is based on the Primary and Study Completion Dates listed in the CT.gov study record. Results of primary outcomes must be submitted no later than 12 months after the study reaches its Primary Completion Date. Results of secondary outcomes must be submitted no later than 12 months after the study reaches its Study Completion Date.
After submission of results, the results are reviewed by NLM staff. This QA review may take up to 30 days. PRS requires Major Review Comments related to results to be addressed within 25 calendar days. Note that the NLM team will post the submitted results to the public website within 30 days of receipt, even if the content has not passed the quality review, however, the publicly visible results will include the NLM flags of Major Review Comments identifying the apparent errors or deficiencies.
IU strongly recommends resolution of all Major Review Comments to ensure clean results without apparent error appear on the public CT.gov site.
Monetary Penalties Associated with Late Results Reporting
When results are required under federal regulations or federal agency policy, failure to submit results within the required timeframe can result in monetary penalties. Per statute, violations can result in an initial $10,000 penalty and up to $10,000 additional per day penalty for the duration of an uncorrected violation. Therefore, monitoring of results reporting timelines and advance planning to meet the required timelines is vital to ensure compliance and avoid potential liability. While IU CT.gov compliance staff will provide advance reminders of upcoming results reporting deadlines when possible, it is ultimately the Responsible Party’s obligation to ensure these timelines are met.
Calculation of Completion Dates
Completion dates are defined by the trial design. The date on which the last participant is examined or receives an intervention for the purposes of final data collection for the trial’s primary outcome is the study’s Primary Completion Date. While the trial is ongoing (i.e., while data collection continues), this date appears as an anticipated date. Once data collection for the primary outcome is completed – whether according to the pre-specified protocol plan or if the protocol is terminated early – the actual date on which the final subject was examined for this purpose must be entered into the CT.gov record.
Similarly, the date on which the last participant is examined or receives an intervention for purposes of final data collection for any secondary outcome measures and adverse events (for example, the last participant’s last visit) – whether the trial was completed according to its pre-specified plan or terminated early – is the Study Completion Date. While the trial is ongoing, i.e., while data collection continues, this date appears as an anticipated date. Once data collection for any secondary measure or adverse event is concluded, the actual date on which the final subject was examined for these purposes must be entered into the CT.gov record.
If a study has only primary outcomes, or if the primary and secondary outcome measures end at the same study timepoint, the Primary and Study Completion Dates should match. The completion dates entered into CT.gov must align with the IRB approved protocol and the status changes submitted to the IRB (e.g., a study in Data Analysis Only with the IRB must have appropriately reported completion dates in CT.gov).
Extension of timeframe for submitting results
Completion of routine data analysis does not permit completion dates to be extended. However, in special circumstances, the Responsible Party can request an extension for good cause. For FDA-regulated mandatory registrations, the extension is requested from and granted by NLM staff. For NIH-funded mandatory registrations, the program officer should be contacted with the extension request. Such requests must be submitted prior to the date on which results information would otherwise be due.
If circumstances cause a PI to consider terminating a trial prior to its originally planned completion (i.e., due to resources, lack of enrollment, etc.), results information is still required for any subjects enrolled. When such a decision is made, the deadline to submit results will be retroactively applied to when the final participant completed their participation once the actual Completion Dates are entered. In these cases, prior to submitting updated completion dates in CT.gov, PIs should consult with the IU CT.gov compliance staff for guidance on how to request a good cause extension if needed.
Problems can occur during the creation and modification of a record on CT.gov. CT.gov identifies several types of problems:
ERROR - Problem is serious. Errors must be addressed prior to release of the CT.gov record.
WARNING, ALERT, or NOTE - Should be reviewed and addressed as needed. These items may lead to the identification of issues during the NLM QA process.
Issues noted in the Problems Column of PRS should be resolved within 30 days of their appearance, or within 14 calendar days of IU CT.gov compliance program instructions for resolution.
Detailed instructions on the PRS website can assist you with problem resolution. Additionally, upon request, the IU CT.gov compliance staff may provide guidance on how to resolve the problems.
Required actions and outstanding issues that are not resolved in a timely fashion by the Responsible Party may be escalated to the Clinical Affairs AVP via email. The Clinical Affairs AVP will be responsible for the process of resolution of such issues and the associated administrative support needed to perform this function.
If you receive any correspondence from an external agency (including the FDA or NIH) regarding potential noncompliance of a CT.gov record, you must notify the Office of Research Compliance at email@example.com immediately.
Clinical Trials.gov resources
Federal regulations, policies and guidance
Other policies and recommendations
- International Committee of Medical Journal Editors "Clinical Trials Registration: A Statement from the International Committee of Medical Journal Editors", September 2004
- International Committee of Medical Journal Editors "Recommendations for the Conduct, Reporting, Editing, and Publication of Scholarly Work in Medical Journals", December 2016
- Centers for Medicare & Medicaid Services "Pub 100-04 Medicare Claims Processing: Transmittal 2955"