ORD Sponsored Clinical Trials: Registration and Submission of Summary Results

Access to clinical trials is critical for VA's ability to advance knowledge and care for Veterans and the nation. The VHA Office of Research and Development (ORD) is committed to informing Veterans and the public about its research and maximizing the impact of the studies it supports. As a leader in the national clinical trials enterprise, ORD has been making clinical trial information available through public registries for more than 15 years. To achieve these goals, Principal Investigators (PIs) of ORD-funded clinical trials are responsible for registering their trials with and submitting summary results to the National Library of Medicine's (NLM) public registry, ClinicalTrials.gov, as a condition of funding. ClinicalTrials.gov provides patients, family members, health care professionals and members of the public easy access to information on clinical trials for a wide range of diseases, conditions, and health problems.

ORD uses the same definition of a clinical trial as the World Health Organization. This definition is "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." VA PIs should note that by applying this definition and registering a clinical trial prior to enrollment of the first participant, the trial will be eligible for publication in International Committee of Medical Journal Editors (ICMJE) member journals and other journals that follow the ICMJE requirements. (For more information, see http://www.icmje.org/recommendations/browse/publishing-and-editorial-issues/clinical-trial-registration.html and/or N Engl J Med 2004;351:1250-1.) For the subset of VA clinical trials that fall under Section 801 of the Food and Drug Administration Amendments Act (FDAAA 801) and the Final Rule for Clinical Trials Registration and Results Information Submission (42 CFR Part 11), registration with ClinicalTrials.gov will also help meet the requirements specified in the law.

VA PIs of ORD-funded trials must register their clinical trial with ClinicalTrials.gov through ORD mechanisms. Upon meeting the trial registration requirement, ORD funding may be distributed in accordance with the study budget and any applicable funding program requirements. Subsequently, PIs are also responsible for providing regular updates on the trial record and ensuring results are reported in ClinicalTrials.gov within the required timeframes.

Information for VA ORD-Funded Investigators

ORD clinical trial PIs are responsible for all aspects of registering and updating trial records and reporting results of their studies in ClinicalTrials.gov. To assist investigators in meeting these requirements, ORD has standardized some processes through the ART Program (ART Website: http://art.puget-sound.med.va.gov). Please note that some steps require direct interaction with the ClinicalTrials.gov Protocol Registration and Results System (PRS).

Protocol Registration Process

VA investigators funded by any ORD program must have their clinical trial protocol registered as a condition of award. Cooperative Studies Program (CSP) clinical trials are registered through their respective CSP Coordinating Center. Investigators are notified of the requirement at the time of award. When all other Just-In-Time (JIT) requirements are completed, investigators are contacted by the ART Program and provided instructions for registering their clinical trial. If you are a PI and have not received an email from the ART Program regarding registration, please contact the appropriate ORD contact noted below.

Overview of steps involved in clinical trial protocol registration:

1. The funding ORD program initiates the registration process through the ART Program.
2. ART emails the PI with instructions for accessing the ART intranet site and completing the data collection form. VA research staff must be logged into the VA network to access the ART intranet
   • If the PI would like to designate a project staff member to complete data entry on their behalf, contact the ART Program at art@va.gov. The PI remains ultimately responsible for the contents/information provided.
3. The PI (or project staff member) completes the clinical trial protocol information on the ART intranet site and submits it.
4. The ART Program uploads the information to ClinicalTrials.gov. When registration is complete, ART emails proof of registration (PDF file) to the PI.
5. The station must upload and submit the PDF proof of registration receipt from the ART Program to eRA Just-in-Time (JIT).
6. The funding ORD program reviews the registration and approves the component in JIT.
   • For CSP trials, ART notifies the CSP Center of the successful registration.

Protocol Record Update Process

To keep the clinical trial information current for the public and to meet ClinicalTrials.gov requirements for maintaining records, protocol records must be updated or verified as correct at least every twelve months. For trials that meet the definition of an “Applicable Clinical Trial" as described in FDAAA 801 and Final Rule, the Final Rule requires that some data elements be updated more rapidly. (See link for summary chart).  All ORD PIs must update the record within 30 days of a change to any of the following: overall recruitment status, recruitment status at any study site, and the last follow-up date for the primary outcome measure (e.g., primary completion date). The ART Program emails PIs when updates to these data elements are excepted.

The ART Program sends an automated email reminder to the PI when a twelve-month update is due. Protocol updates, like registrations, are completed using the ART Website. Updates are required at least every twelve months until the study is completed. Failure to provide updates in a timely manner will impact project funding. The funding ORD program is notified of trials overdue for an update.

Results Submission Process

PIs of ORD funded clinical trials must submit summary results for their clinical trials to ClinicalTrials.gov. This requirement applies to all ORD trials regardless of whether the trial meets the definition of an "Applicable Clinical Trial" as described in FDAAA 801 and the Final Rule. Summary results information must be submitted within one year of the study Primary Completion Date. This requirement represents a higher standard that VA has chosen to honor its commitment to Veterans. The Primary Completion Date is the date the final subject was examined or received an intervention for the purposes of final collection of data for the primary outcome. This date is specified by the PI in the protocol information. ORD PIs must meet the deadlines for reporting results information to ClinicalTrials.gov. Failure to report results in timely manner will impact project funding and eligibility for future ORD funding.

Before submitting results information, ORD strongly encourages PIs to review the ClinicalTrials.gov PRS Guided Tutorials. If you need assistance during the data entry process, please contact the ART Program. Should PIs need additional guidance on reporting scientific information in the PRS modules, they may be referred to ClinicalTrials.gov staff for assistance.

Overview of Steps for Clinical Trial Results Submission:

1. The ART Program emails the PI in advance of the due date. ART grants the PI permissions to edit the trial record in the PRS and includes login instructions in the email. ClinicalTrials.gov PRS is accessed at https://register.clinicaltrials.gov.
2. The PI should begin preparing results data for submission several months in advance of the submission deadline
   • For information on preparing for data entry, see ClinicalTrials.gov How to Submit Results.
3. The PI or designee enters results in the PRS.
   • If assistance is needed during results data entry, please contact ART@va.gov.
4. When data entry is complete, the PI sets the record status to "Entry Completed.”
   • The PI should ensure that the record is consistent with the ClinicalTrials.gov Results Review Criteria before marking as "Entry Completed."

5. The ART Program reviews the record for problems that need to be addressed prior to releasing (submitting) to ClinicalTrials.gov. When a record meets the required review criteria, then ART releases the record in PRS for ClinicalTrials.gov staff review.
6. A ClinicalTrials.gov staff member will review the study record after it is released and before it is posted on ClinicalTrials.gov. This review focuses on apparent validity (when possible), meaningful entries, logic and internal consistency, and formatting.
• For Applicable Clinical Trials, ClinicalTrials.gov must post the results information within 30 days of submission even if the submission has not completed the ClinicalTrials.gov review process.

7. Upon completion of the review, the PI will receive notification from ClinicalTrials.gov and the ART Program that the results have been accepted or additional changes are required.

• If changes are required, the PI must return to the PRS, address the PRS Review Comments, and mark the record status as "Entry Completed.” ART will then release the record again for review by ClinicalTrials.gov staff.

8. If there are questions about the comments, it is recommended that the PI or designee contact ART staff for assistance. For Applicable Clinical Trials, PIs must correct or address within 25 days any apparent errors, deficiencies and/or inconsistencies that are identified during the review process.
9. Depending on study design and other factors, the PI may need to enter additional summary results at a later date.

ORD Clinical Trials Points of Contact

Questions concerning ORD trial protocol registration, results reporting, or policies can be directed to the following points of contact:

Investigators, Scientific Review and Management (ISRM)
Email: clin-review@va.gov

Cooperative Studies Program
Email: csp@va.gov  
(Study Chairs may also contact their CSP Coordinating Center.)

ART Program
Questions concerning the ORD ART Website or ClinicalTrials.gov can be directed to:
E-mail: ART@va.gov