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.

Upon notification of funding approval from an ORD service/program, VA PIs must register their clinical trial by entering protocol information in ClinicalTrials.gov through ORD mechanisms. Upon meeting this requirement, ORD funding may be distributed in accordance to the study budget and any applicable funding service/program requirements. Subsequently, PIs are also responsible for providing regular updates on the study and ensuring results are reported in ClinicalTrials.gov.

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). ART is a leveraged system for all ORD and supported by the Health Services R&D Service. 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 research service (Clinical Science, Health Services, and Rehabilitation) 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 Service contact noted below.

Overview of steps involved in clinical trial protocol registration:

1. The funding ORD Service initiates the process by notifying the ART Program that a clinical trial requires registration.
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 does not have access to the VA network, contact the appropriate ORD Service contact below.
   • 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. However, please note that 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. Just-in-Time Notification
   • If the Just-in-Time (JIT) process for this project was initiated in the VA JIT Document Manager, ART sends notification to the JIT system that the registration has been completed through an automated process.
   • If the JIT process was initiated in the eRA Commons JIT module, the station must upload the PDF proof of registration receipt from the ART Program to eRA JIT.
6. The funding ORD service 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. PIs must also 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 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 every twelve months until the study is completed. Failure to provide updates in a timely manner will impact project funding. The funding ORD service 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. Results information includes: Participant Flow, Baseline Characteristics, all pre-specified Primary and Secondary Outcomes, and Adverse Events.

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 PI prepares results data for submission.
   • For information on preparing for data entry, see ClinicalTrials.gov How to Submit Results.
2. ART grants the PI permissions to edit the trial record in the PRS and sends an email with login instructions. The ClinicalTrials.gov PRS is accessed at https://register.clinicaltrials.gov.
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 Protocol Review Criteria (PDF) and the ClinicalTrials.gov Results Review Criteria (PDF) 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. If the record meets the required review criteria, then ART releases the record in PRS for ClinicalTrials.gov staff review.
   • 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.
6. 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 for review by ClinicalTrials.gov staff.
   • If there are questions about the comments, it is recommended that the PI or designee contact ART staff for assistance. ART staff may refer the PI togov staff at register@clinicaltrials.gov to request clarification and/or assistance in resolving the comments.
7. Once accepted, results are posted to the ClinicalTrials.gov website.
8. 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

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

Clinical Science Research & Development Service
Kristina Nord, MSW
Research Health Science Specialist
Phone: (202) 443-5614
Email: kristina.nord@va.gov

Health Services Research & Development
Christine Nguyen, MHA, PMP
Research Health Science Specialist
Phone: (202) 443-5797
Email: christine.nguyen@va.gov

Tiffin Ross-Shepard, BS
Scientific Merit Review Manager
Phone: (202) 443-5776
Email: tiffin.ross-shepard@va.gov

Rehabilitation Research & Development Service
Shirley Groer, PhD
Scientific Program Manager
Phone: (202) 443-5767
Email:shirley.groer@va.gov

Cooperative Studies Program
Amanda P. Garcia, MPH
Program Analyst, CSP Central Office
(202) 443-5383
Email: amanda.garcia@va.gov
(Study Chairs may also contact their CSP Coordinating Center.)

Grant Huang, MPH, PhD
Deputy Chief R&D Officer - Enterprise Optimization
Chair, ORD Clinical Trials Registration & Results Work Group
Phone: (202) 443-5700
Email: CSP@va.gov

ART Program Contact

Questions concerning the ART Website or PRS access can be directed to:
Jolie Bergman
Coordinator, ART Program
Phone: (206) 277-4163
E-mail: ART@va.gov