ClinicalTrials.gov Requirements

About ClinicalTrials.gov

ClinicalTrials.gov is a public database containing information about federally and privately supported clinical trials for an array of diseases and conditions.  A service of the U.S. National Library of Medicine (NLM)at the National Institutes of Health (NIH), and in collaboration with the Food and Drug Administration (FDA), ClinicalTrials.gov requires registration and results reporting for clinical trials.  Background information regarding history, policies, and laws can be found on ClinicalTrials.gov Section 801 of the Food and Drug Administration Act (FDAAA 801) specifies registration and results reporting requirements for clinical trials (for full documentation describing the law, see FDAAA 801). Pubic information can be found at www.clinicaltrials.gov, but investigators wishing to publish on ClinicalTrials.gov must do so in the Protocol Registration and Results System (PRS) at register.clinicaltrials.gov. The purpose of this page is to help investigators at the University of Iowa (UI) understand their responsibilities for ClinicalTrials.gov registration and results reporting.

Final Rule Update

The U.S. Department of Health and Human Services has issued a final rule (42 CFR 11) about ClinicalTrials.gov.  For more information, please see the HHS news release and NIH Office of Science Policy blog post.  The Final Rule became effective on January 18, 2017, is required to be applied at all institutions no later than April 18, 2017. Institutions found in violation of this rule could be subject to civil penalties of up to $11,383, as well as an additional $11,383 per day, if the issue is not resolved within 30 days. Additionally, funding to the institution can be reduced or stopped until this issue is resolved, and this could impact future funding for the institution. Besides civil penalties, criminal penalties are also possible for investigators found in non-compliance of this rule. A checklist-based tool to assist responsible parties in evaluating whether a study is an applicable clinical trial based on 42 CFR 11.22(b) for studies initiated on or after 1/18/17 is now available here

1. Registration

a. Who is required to register?

b. When must I register on ClinicalTrials.gov?

c. What must I do after registration?

 

2. Applicable Clinical Trials (ACT)

3. Applicable Deadlines

4. NIH and ICMJE Reporting Requirements

5. Results

6. Observational and Expanded Access Studies

7. Protocol Registration and Results System (PRS)

8. IRB and ClinicalTrials.gov

a. HawkIRB

9. PRS Administrators

10. Who Can Answer Questions at UI?


 

1.  Registration

Registration is required for all Applicable Clinical Trials (ACT). To register a study, investigators must use the Protocol Registration and Results System (PRS) at www.register.clinicaltrials.gov. To get started, investigators should contact a PRS administrator by emailing ct-gov@uiowa.edu to have an account created for them. Once a user is registered in the system, they will be able to add new projects in the PRS at any time. The University of Iowa maintains their own records for ClinicalTrials.gov, but these are reviewed and published by the PRS team. These records are overseen by PRS administrators for the institution.

a. Who is Required to Register?

Clinical trials registration and results reporting is required by law.  At the University of Iowa, the Principal Investigator (PI) is considered the responsible party for all clinical trials, unless the study is industry sponsored. When registering a study, the term ‘Sponsor-investigator’ should be selected. In the PRS, the term ‘Principal Investigator’ defines a situation where the sponsor of the study designates a University of Iowa Principal Investigator as the responsible party or the record. If the sponsor is not a University of Iowa faculty or staff member, the responsibility of reporting to ClinicalTrials.gov falls upon the sponsor who initiated the study protocol.  

If one of the following examples applies to you or your study, you would likely be considered a sponsor-investigator:

You hold the Investigational New Drug Application (IND) or the Investigational Device Exemption (IDE) for your study (responsible party = sponsor-investigator);

Your study involves the UI serving as the coordinating center for a clinical trial under a prime award (as opposed to a subcontract) and the trial is investigator-initiated;

You do not hold the IND or IDE for your study, but you know that your Sponsor/funding agency has delegated you the responsibility to comply with the registration requirements (or if you can easily ascertain this from your contract or other award documentation); and/or

The clinical trial is regulated by the FDA (phase II through IV trial) and involves a drug, biologic or device, but does not require an IND/IDE.

For studies that have the UI as the IRB of record, the HawkIRB application captures trial information and NCT# in Section VII.B.1.  Entering a NCT# is required for Phase 2-4 studies and is currently optional for Phase 1 studies.

Your study involves a clinical trial and has NIH funding.

Find more information at ClinicalTrials.gov under "Who is Responsible for Registering Trials and Submitting Results?" 

b. When must I register on ClinicalTrials.gov?

Registration must be completed with ClinicalTrials.gov within 21 days of enrollment of the first subject in a trial and updated at least every 12 months.  For more information, see ClinicalTrials.gov (“Which Trials Must Be Registered and Have Results Submitted to ClinicalTrials.gov?”). Additionally, studies involving NIH funding, or which plan to publish in ICMJE or other journals, will have additional requirements to consider for registration on ClinicalTrials.gov (please see ‘NIH and ICMJE Reporting Requirements’ section). To publish in an ICMJE journal, for example, requires registration prior to enrolling the first subject.

 

Below is a table indicating when registration requirements apply:

 

Applicability of Requirements in 42 CFR Part 11

c. What to Do After Registration

Registering in ClincalTrial.gov’s PRS system is only the first step. FDAAA 801 and the Final Rule require reporting of results, adverse events (expected and unexpected), as well as modifications or updates to the study. Additionally, there may be other guidelines to follow if the study has NIH funding, or is planned to be published in an ICMJE, or other journal. These organizations each have their own rules for adhering to the Final Rule and FDAAA 801, which should be considered. The record should be checked and updated often. The University of Iowa IRB will facilitate the process of informing sponsor-investigators when updates are needed. In addition to keeping a record up to date, the record must be reviewed and approved by the responsible party at least yearly, even if nothing has changed. A record may be changed by the responsible party or the record owner at anytime, but it is recommended to make necessary changes after IRB review as the IRB may decide additional changes are needed, which could create extra work for the investigator.

 

2. Applicable Clinical Trials (ACT)

To determine if your study is an ACT requiring registration, use the checklist below. This checklists consists of several additional pages of points to consider, but these exceptions will be evaluated by the University of Iowa PRS administrators and IRB, who will inform the investigator when they apply. In addition to this checklist, many funding applications and FDA documents require specific language when an ACT is involved, and these organizations may help in making the determination of an Applicable Clinical Trial. For a full document, please use the link at the bottom of this page.

CT.gov ACT Criteria
*Checklist taken from https://prsinfo.clinicaltrials.gov/ACT_Checklist.pdf
A Clinical Trial is considered an Applicable Clinical Trial (ACT) when the above criteria are met. More information can be found here.

 

3. Applicable Deadlines

Data Element

Deadline for Updating 

(i.e., not later than the Specified Date)

Study Start Date

30 calendar days after the first subject is enrolled

Overall Recruitment Status

30 calendar days after a change in overall recruitment status

  • If the overall recruitment status is changed to "suspended," "terminated," or "withdrawn," the Why Study Stopped data element must be updated at that time as well

IRB Approval Status

30 calendar days after a change in status

Primary Completion Date

30 calendar days after the clinical trial reaches its actual primary completion date

Enrollment

At the time the primary completion date is changed to "actual," the actual number of participants enrolled must be submitted

Study Completion Date

30 calendar days after the clinical trial reaches its actual study completion date

Responsible Party, by Official Title

30 calendar days after a change in the Responsible Party or the official title of the Responsible Party

Responsible Party Contact Information

30 calendar days after a change in the Responsible Party or the contact information for the Responsible Party

Device Product not Approved or Cleared by US FDA

15 calendar days after a change in approval or clearance status has occurred

Record Verification Date

Any time the Responsible Party reviews the complete set of submitted clinical trial information for accuracy and not less than every 12 months, even if no other updated information is submitted at that time.

*Table Shared by Stanford University

 

4. NIH and ICMJE Reporting Requirements 

Element Final Rule NIH Policy ICMJE Policy
Scope/Applicability

Applicable clinical trials of FDA-regulated drug, biological, and device products and pediatric post-market surveillance studies of devices required by the FDA under the FD&C Act.

Does not apply to phase 1 trials or small feasibility studies.

Applicable clinical trials are (1) clinical trials of drug and biological products that are controlled, clinical investigations, other than phase 1 investigations of a product subject to FDA regulation; and (2) prospective clinical studies of health outcomes comparing an intervention with a device product against a control in humans (other than small feasibility studies) or any pediatric post-market surveillance studies required by FDA under the FD&C Act.

Applies to public and private sector sponsors and other entities who meet the definition of a responsible party.

All clinical trials funded wholly or partially by NIH.

Includes phase 1 clinical trials and trials that do not involve any FDA regulated product such as trials involving only behavioral interventions.

Applies to NIH-funded clinical trials where applications or proposals are received by NIH on or after the policy’s effective date.

Applies to NIH-conducted clinical trials initiated on or after the policy’s effective date.
All clinical trials which wish to publish in an ICMJE journal, or its affiliates, must register prior to enrolling the first subject. Currently, only registration is mandated.

Timeframe for registration on ClinicalTrials.gov

Not later than 21 days after enrollment of the first participant.

Not later than 21 days after enrollment of the first participant.

Prior to enrollment of first subject.

Registration data elements to be submitted to ClinicalTrials.gov

Elements defined in the final rule. Consists of descriptive information, recruitment information, location and contact information, and administrative data.

Elements defined in the final rule. Consists of descriptive information, recruitment information, location and contact information, and administrative data.

Elements defined in the final rule. Consists of descriptive information, recruitment information, location and contact information, and administrative data.

Timeframe for results information submissions to ClinicalTrials.gov

Not later than 12 months after primary completion date; possible delay of up to an additional 2 years for trials of unapproved products or of products for which initial FDA marketing approval or clearance is being sought, or approval or clearance of a new use is being sought.

Not later than 12 months after primary completion date; possible delay of up to an additional 2 years for trials of unapproved products or of products for which initial FDA marketing approval or clearance is being sought, or approval or clearance of a new use is being sought.

Not mandated in policy, but must meet the requirements of FDAAA 801.

Results data elements to be submitted to ClinicalTrials.gov

Elements defined in the final rule. Includes participant flow, demographic and baseline characteristics, outcomes and statistical analyses, adverse events, the protocol, and statistical analysis plan, and administrative information.

Elements defined in the final rule. Includes participant flow, demographic and baseline characteristics, outcomes and statistical analyses, adverse events, the protocol, and statistical analysis plan, and administrative information.

Elements defined in the final rule. Includes participant flow, demographic and baseline characteristics, outcomes and statistical analyses, adverse events, the protocol, and statistical analysis plan, and administrative information.

Potential Consequences of Non-compliance

  • Identifying clinical trial record as non-compliant in ClinicalTrials.gov
  • For Federally funded trials, grant funding can be withheld if required reporting cannot be verified.
  • Civil monetary penalties of up to $11, 383 per day
  • May lead to suspension or termination of grant or contract funding
  • Can be considered in future funding decisions
  • Identifying clinical trial record as non-compliant in Clinical Trials.gov
  • Inability to publish in ICMJE or affiliated journal

Effective date

1/18/2017

1/18/2017

Currently in effect

Compliance Date

4/18/2017

4/18/2017 N/A
*Table elements taken from https://www.nih.gov/news-events/summary-table-hhs-nih-initiatives-enhance-availability-clinical-trial-information

NIH and ICMJE affiliates (as well as many other journals) have even more stringent criteria for submitting to ClinicalTrials.gov. It is recommended that each PI be aware of each of these rules, or to practice following the most stringent of these to assure compliance.

 

5. Results

All Applicable Clinical Trials are required to report results. Additionally, all clinical trials which have NIH funding must report results information. In general, the law and federal funding entities require responsible parties to report summary results information for interventional studies of drugs, biological products, and devices within 1 year of the primary completion date of the study, regardless of the funding source, presence of statistically significant findings, or journal publication status. Prior to submitting results data, it is recommended you review the “How to Submit Your Results” guidance on ClinicalTrials.gov.

 

6. Observational and Expanded Access Studies

Both Observational and Expanded Access Studies can be registered in ClinicalTrials.gov’s PRS system; however, neither are considered Applicable Clinical Trials requiring registration. Please note that expanded access studies are not Applicable Clinical Trials, but if expanded access is offered for a drug or biologic, there must be a separate expanded access record created. The expanded access record is only the responsibility of the UI sponsor-investigator when they are both the sponsor and manufacturer of the drug or device. In most circumstances, the manufacturer is the responsible party of expanded access records. When expanded access is available, sponsor-investigators must indicate so in their record and provide the NCT number of the expanded access record. Expanded access records exist separately from the study record.

 

7. Protocol Registration and Results System (PRS)

The Protocol Registration and Results System (PRS) is the term used for the database where information published on ClinicalTrials.gov is entered. The PRS consists of 2 sections: the Protocol Section and the Results Section. The Protocol section is where registration information is entered, and the Results Section is where results information and information on participants is entered. Each section is broken down into modules where specific information can be entered. The system, like HawkIRB, if very complex, but becomes easier to use after becoming acclimated with the modules. The PRS offers help and advice for completing each module via the ‘Definitions’ and ‘Help’ links on each page. These links work in much the same way as the HawkIRB help icons in that they describe exactly what the section is looking for. Additional information and training can be found on the ClinicalTrials.gov public site under the ‘Submit Studies’ tab. University of Iowa researchers should contact their PRS Administrator at ct-gov@uiowa.edu with additional questions. Please note the following University Policies when using the PRS:

  1. Users must input the IRB number (123456789) as the ‘Unique Protocol ID’
  2. Users should list themselves as ‘Sponsor-Investigator’
  3. The University of Iowa should not be listed as the sponsor for any study, unless otherwise instructed to do so
  4. The ‘Oversight’ module should list the IRB contact information as:

Board Status: Approved     Approval Number: 123456789

Board Name: University of Iowa IRB 01

Board Affiliation: University of Iowa

Phone: 319-335-6564   Email: irb@uiowa.edu

Address:

Human Subjects Office / IRB

Hardin Library, Office 105

600 Newton Rd

Iowa City, IA 52242-1098

  1. Contact information should be for the study team and not the IRB

 

8. IRB and ClinicalTrials.gov

The University of Iowa IRB considers the ClinicalTrials.gov record in its approval. It is recommended that the HawkIRB application be submitted first to avoid needing to make additional changes to the PRS record. In addition, the IRB reviewers and PRS administrator will assist in assuring the record is updated appropriately. The NCT number in the IRB application can be left blank until the number has been assigned. This number can be updated in the IRB application at any time through a modification, or by emailing the ct-gov@uiowa.edu to request that an existing application be returned.

 

a. HawkIRB

Section VII.B of the HawkIRB application is where you will identify your clinical trial and find the link to the ClinicalTrials.gov database to register your study. VII.B.1 should identify ‘Clinical Trial’ as the study type, and additional questions can be answered, as appropriate. Changes to the HawkIRB system are currently underway to facilitate communication with the PRS system. Once the changes occur, much of the information will be automated into the PRS, making the maintenance and registration in the PRS easier for investigators. 

 

9. PRS Administrator

PRS administrators monitor records for the institution, provide help and feedback on using the system, create and monitor accounts for the PRS, and inform investigators of issues needing resolution in the PRS system. Additionally, the PRS administrator reviews study applications involving clinical trials for the IRB and communicates relevant information to them. The PRS administrator at the University of Iowa is Brian Brotzman.

In addition to the PRS administrator, most departments have departmental liaisons who work directly with the PRS administrator and provide education and training to their department on entering data in the PRS.

 

 

10. W​ho Can Answer Questions at UI?

The Human Subjects Office has partnered with several departments, to assist University of Iowa researchers with questions related to ClinicalTrials.gov requirements. The PRS Administrator will refer you to the appropriate departmental liaison to assist in completing your records.

Individuals with questions or applying for an account with ClinicalTrials.gov through UI should contact:

Brian Brotzman
Protocol Registration and Results System (PRS) Administrator at UI
Phone: 319-384-4623
Email: ct-gov@uiowa.edu(link sends e-mail)