CTRR Taskforce FAQ

The “Study Sponsor” is responsible for ensuring the clinical trial is registered to ClinicalTrials.gov. Industry-Sponsors are responsible for registration, maintenance, and results reporting to ClinicalTrials.gov in most cases.

Principal Investigators are ultimately responsible for ensuring ClinicalTrials.gov registration if one or more of the following apply:

1. The trial is an Investigator-Initiated Trial (IIT)
2. The trial is federally sponsored, and the Principal Investigator’s Institution is the only study site or the coordinating center
3. The Investigator holds the IND for the agent being studied or the IRB has determined the agent is IND exempt
4. The Investigator holds an IDE for the device being studied or the IRB has determined it to be of non-significant risk (NSR)

Click for link to Elaborations of Definitions of Responsible Party and Applicable Clinical Trials.

Click for Link to FAQs on ClinicalTrials.gov

The sponsor can designate the Principal Investigator as the responsible party under certain conditions. Link below to the ClinicalTrials.gov FAQ.

Click for link to FAQs on ClinicalTrials.gov

Registration is required when any of the following are met:

1. “Applicable Clinical Trials” (ACTs) per the Food and Drug Administration (FDA) require registration to ClinicalTrials.gov within 21 days of first participant enrollment. These are Interventional, Phase 2-4 trials that study an FDA regulated drug, biologic, or device product.
2. Per the NIH Policy on the Dissemination of NIH-funded Clinical Trials Information, NIH-funded clinical trials require registration within 21 days of first participant enrollment. NIH has a decision tree to determine if the study is a clinical trial. The NIH award letter will indicate ClinicalTrials.gov expectations. Data Management and Sharing Plans required by NIH as a contingency of funding can be outlined in the Individual Participant Data (IPD) Sharing section of the ClinicalTrials.gov record to be populated at the time of registration.
3. Qualifying clinical trials of therapeutic intent that evaluate an item or service that falls within the Medicare benefit category per the Centers for Medicare and Medicaid Services (CMS) require registration to ClinicalTrials.gov.
4. Registration is required as a condition to receive funds for human research (Observational or Interventional) funded by the US Department of Veterans Affairs – Office of Research and Development. Prospective Data Sharing Plans are required for all VA ORD funded human research, this plan can be documented in the IPD Sharing section of the ClinicalTrials.gov record at registration.
5. Interventional clinical trials per International Committee of Medical Journal Editors’ (ICMJE) guidance are required to be registered to a public database (including ClinicalTrials.gov) prior to first participant enrollment as a contingency for subsequent publication in journals that follow this guidance. ICMJE requires IPD Sharing section of the ClinicalTrials.gov record to be populated with an answer of either ‘Yes’ or ‘No’ at the time of registration. They do not consider ‘Undecided’ a valid answer to whether there will be an IPD data sharing plan.
6. Patient-Centered Outcomes Research Institute (PCORI) funded studies, Interventional, Observational, and Patient Registries are required to have a ClinicalTrials.gov record before the first participant’s enrollment. Data sharing plans contractually required by PCORI can be populated in the IPD Sharing Plan section of the ClinicalTrials.gov record at registration.
7. The World Health Organization (WHO) documents a joint statement based on the World Medical Association’s (WMA) Declaration of Helsinki acknowledging a commitment to public clinical trial disclosure and encourages the documentation of an IPD Sharing Plan. A list of international, non-governmental signatories that have agreed to uphold this commitment can be found on the WHO website.

A summary table of information presented here for Registration as well as and Results Requirements (see Results Requirements section of FAQs) per ICMJE Guidance, NIH Policy, FDAAA Law, CMS Policy, VA ORD Policy, PCORI Contracts, WHO, and WMA Principles is linked here.

The study is considered registered once it has received an NCT (National Clinical Trial) number. The NCT Number is assigned after the protocol information has been Released (i.e., submitted) by the Responsible Party and passes ClinicalTrials.gov Protocol Registration and Results System (PRS) Review (i.e., no Major Comments have been issued by PRS). PRS Review of initial registration can take about 2-5 business days, but there are times when the PRS experiences higher volumes of submissions and review can take over 10 days. Once the review is completed, an e-mail notification from PRS containing the NCT Number is sent to the PRS User who last edited the record and to the Record Owner. The record will then be available to the public on ClinicalTrials.gov within 2 business days of receipt of the NCT number.

Of note, ICMJE uses the date trial registration materials were first submitted to a registry as the date of registration; however, when there is a substantial delay between the submission of registration materials and their posting to the trial registry, journal editors may inquire about the circumstances that led to the delay. Because of this, and because publication is a key outcome for many institutions, some choose to make receipt of an NCT number prior to enrollment of the first participant an institutional requirement. This also ensures compliance with federal timelines to register if the study is also an NIH-funded clinical trial and/or an ACT.

Per FDAAA regulations, the requirement is to submit required information regardless of when the NCT number is assigned.

The Primary Completion Date (PCD) is the date the final participant was examined or received an intervention for the purposes of final collection of data for the primary outcome, whether the study concluded according to the pre-specified protocol or was terminated. In the case of clinical studies with more than one primary outcome measure where data is collected over different Time Frames, this term refers to the date upon which data collection is complete from all enrolled participants for all of the primary outcomes. The definition is participant-centric, and, in general, “collected” means when data are obtained from an enrolled participant.

Once the study has reached the PCD, the Responsible Party must update the PCD from Anticipated to Actual in the ClinicalTrials.gov record within 30 days.

For Applicable Clinical Trials per FDAAA Law and NIH-funded clinical trials, results will be due one year from the PCD. Because the federal due date for results hinges on the accurate and timely entry of the PCD, it is imperative that study teams understand the PCD definition and the requirements surrounding its update.

Dates that study teams might mistakenly enter as PCD include:

1. Date that enrollment closed
2. Date the data was analyzed
3. Date the data was gathered from all sites
4. Date the protocol was closed with the IRB
5. Date of publication
6. Date the protocol was terminated

To the extent possible, PRS Administrators should crosscheck the CTMS and IRB application materials to identify these errors before they are released to the public ClinicalTrials.gov site (if the institution is the Responsible Party) and/or also educate the research community about these potential errors and their implications.

Common PCD Questions:

Question 1: If tissue samples (blood, biopsy, etc.) are collected from a participant per protocol to answer a Primary Outcome, is the PCD the date that the last sample was collected or the date that the last sample was analyzed?

Answer 1: Per the PCD definition and the ClinicalTrials.gov FAQs, the PCD is the date the last sample was collected from the last participant and NOT the date that it was assessed, analyzed, or interpreted.

Question 2: If participant survey responses are collected or telephone interviews are conducted with a participant per protocol to answer a Primary Outcome, how does this inform the PCD?

Answer 2: Per the ClinicalTrials.gov FAQs, there are a broad range of data collection methods inferred in FDAAA Law, including examination via phone or electronic means. If the study employes survey responses or telephone interviews to answer a Primary Outcome, it would be legally permissible to use the date of the last participant’s survey conducted / received or the date of the last participant’s telephone interview, as applicable, as the PCD. The same would be true if the examination was via telephone or other electronic means. If the survey is via paper sent through the mail, it is permissible to use date of receipt in the mail as the date of data collection.

Question 3: What is the PCD for Terminated Trials?

Answer 3: The PCD for Terminated Trials remains the date the final participant was examined or received an intervention for final collection of data for the primary outcome. It is NOT the date upon which the trial was terminated. Bear in mind that if an ACT (or NIH-funded clinical trial) is terminated and the PCD occurred over a year ago, this means results are now late and an update of the PCD in the public record would indicate as such. This highlights the importance of monitoring how long it has been since the last participant was enrolled and had data collected from them. To that end, some institutions have created processes whereby slow accruing ACTs and/or NIH-funded clinical trials are flagged by the institution. This is so a long lag in enrollment in a trial that is ultimately terminated doesn’t result in a PCD over 1 year ago, creating a late results record.

Given these scenarios, consider submitting a Good Cause Extension (GCE) request. More information about GCE results requests is available in this linked document https://ctrrtaskforce.org/wp-content/uploads/2024/05/Requesting-Results-Extensions-and-Delay-Certifications.pdf

The date the final participant was examined or received an intervention for purposes of final collection of data for the primary and secondary outcome measures and adverse events (for example, last participant’s last visit), whether the study concluded according to the pre-specified protocol or was terminated.

With respect to an overall survival endpoint, the time frame for assessment should be pre-specified in the protocol and the SCD should be entered in accordance with that pre-specification. Bear in mind the overall survival endpoint time frame is an estimate. Once the last subject is evaluated, the actual time frame will be known and must be updated.

Once the study has reached the SCD, the Responsible Party must update the SCD from Anticipated to Actual in the ClinicalTrials.gov record within 30 days.

Dates that study teams might mistakenly enter as SCD include:

1. Date that enrollment closed
2. Date the data was analyzed
3. Date the data was gathered from all sites
4. Date the protocol was closed with the IRB
5. Date of publication
6. Date the protocol was terminated

To the extent possible, PRS Administrators should crosscheck the CTMS and IRB application materials to identify these errors before they are released to the public ClinicalTrials.gov site (if the institution is the Responsible Party) and/or also educate the research community about these potential errors and their implications.

Summary Results data are required to be reported to ClinicalTrials.gov for:

1. Applicable Clinical Trials (ACTs) (subject to FDAAA 801 and 42 CFR Part 11) no later than 12 months after the Primary Completion Date, defined as the date the final participant was examined or received an intervention for purposes of final collection of data for the Primary Outcome(s).
2. NIH-funded clinical trials per the NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information, no later than 12 months after the Primary Completion Date, defined as the date the final participant was examined or received an intervention for purposes of final collection of data for the Primary Outcome(s).
3. US Department of Veterans Affairs – Office of Research and Development
4. Patient-Centered Outcomes Research Institute (PCORI) funded studies require result reported as soon as possible and if relevant, the earlier of the two: no less than 30 days from the draft final report due to PCORI or as required per FDAAA Law. Results submission time-lines are determined per PCORI contract.
5. The World Health Organization (WHO) documents a joint statement based on the World Medical Association’s (WMA) Declaration of Helsinki acknowledging a commitment to public clinical trial disclosure. A list of international, non-governmental signatories that have agreed to uphold this commitment can be found on the WHO website.

The International Committee of Medical Journal Editors (ICMJE) does not require results reporting to ClinicalTrials.gov, but rather only requires registration on ClinicalTrials.gov prior to enrollment of the first participant.

In ethical obligation to the participant and the community at large, summary results are encouraged per the WMA Declaration of Helsinski to be reported whether they are required by law or policy.

A summary table of information presented here for Registration and Results Requirements per FDAAA Law, NIH Policy, CMS Policy, VA ORD Policy, ICMJE Guidance, PCORI Contracts, WHO, and WMA Principles is linked here.

1. Failure to comply with FDAAA Law may result in civil monetary penalties up to $10,000 per day (adjusted for inflation), loss of Health and Human Services funding, FDA Sanctions (483 Letter), and public Notice of Noncompliance.
2. The FDA posts all Pre-Notices of Potential Noncompliance at this link.
3. Failure to comply with NIH Policy may result in a loss of funding and restrictions on continuations (managed by NIH Office of Policy for Extramural Research Administration (OPERA))
   1. If the NIH-funded clinical trial is also an ACT, an institution-wide hold on funds may result.
   2. Federal Awardee Performance and Integrity Information System (FAPIIS) referral (now curated at gov)
4. Failure to comply with CMS Policy may result in delayed initiation of study and delayed or denied billing.
5. Failure to comply with VA ORD Policy may result in loss of VA funding.
6. Failure to meet ICMJE requirements may result in refusal to publish in any journal that adopts ICMJE guidance.
7. Failure to meet contractual obligation per PCORI funding may result in consequences as outlined in the funding contract.
8. Consequences with failure to meet World Health Organization (WHO) and World Medical Association’s (WMA) guidance would be specific to the funding entity or signatory.
9. If an ACT, public listing on the FDAAA Trials Tracker, including how many days late.

No. Per ICMJE, reporting results in a tabular format to ClinicalTrials.gov in compliance with FDAAA 801 is not considered ‘prior publication’.

For Applicable Clinical Trials (ACTs), subject to FDAAA 801 and 42 CFR Part 11, results are required to be submitted to ClinicalTrials.gov no later than 12 months after the Primary Completion Date. This requirement indicates that results submitted by the due date comply with FDAAA Law. NIH has adopted the results reporting requirements of FDAAA Law for all NIH-funded clinical trials.

If the intent is to deliver Summary Results to the public within one year of PCD, then it is recommended to submit the initial results up to 2 months in advance of the due date to have enough time for the PRS review process and subsequent required corrections. This is because initial results review by ClinicalTrials.gov PRS takes up to 25 days for Applicable Clinical Trials and NIH-funded Clinical Trials. This does not take into account the additional time it takes to respond to PRS Review Comments.

Of note, because the Participant Flow and Baseline Characteristics sections of the Results Module require data that may be available prior to statistical analysis of outcome measure data, study teams can populate these sections of the Results Module early.

Follow the PRS Guided Tutorials for step-by-step instructions for entering study results.

Scope & Applicability

Effective January 18, 2017, NIH-funded clinical trials – per NIH’s clinical trial definition (see below) – are within the scope of the NIH-Policy on the Dissemination of NIH-funded Clinical Trial Information.

More specifically, the policy applies to clinical trials funded through NIH’s extramural program if the grant, other transaction, or contract was submitted on or after the effective date.that requests support for a clinical trial initiated (i.e., enrolled the first participant) on or after the effective date. The policy also applies to clinical trials funded through NIH’s intramural program if the clinical trial was initiated (i.e., enrolled the first participant) on or after the effective date.

A clinical trial does not fall under NIH’s policy if the trial uses NIH-supported infrastructure but does not receive NIH funds to support its conduct. (Example: Facility in which the clinical trial will be conducted was built with NIH funded, but the clinical trial itself is not funded by NIH.)

Both the Funding Opportunity Announcement (clinical trial or not) and the subsequent award letter will document the relevance to NIH Policy. The award letter will indicate expectations relevant to ClinicalTrials.gov as a contingency of funding.

NIH Clinical Trial Definition

A clinical trial is defined by the NIH 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.”

Note that, unlike the definition of Applicable Clinical Trial (ACT), the NIH’s clinical trial definition is not restricted to certain study phases or restricted to only include studies evaluating FDA-regulated interventions.

Further, a given study meets the NIH definition of a clinical trial, even if

1. It studies healthy participants
2. The study does not have a comparison group (e.g., placebo or control)
3. The study is only designed to assess the pharmacokinetics, safety, and/or maximum tolerated dose of an investigational drug
4. The study is utilizing a behavioral intervention
5. Only one aim or sub-aim of the study meets the clinical trial definition

To best understand the types of studies considered clinical trials by NIH, it is strongly recommended that institutions review the NIH’s case study examples at the following link https://grants.nih.gov/policy/clinical-trials/case-studies.htm#collapseS2_NIDDK_8.

Carr, S. and Gordon, V., NIH Policy on Dissemination of NIH-Funded Clinical Trial Information, presented to the Clinical Trials Registration and Results Reporting Taskforce on 12/15/2016.