UC Denver Anschutz's Clinical Research Support Center ClinicalTrials.gov Tips of the Week

Per NIH policy, Registration and Results information must be submitted to ClinicalTrials.gov for all clinical trials funded wholly or partially by NIH.  The policy applies if the funding application (including a competing renewal application if it includes a new clinical trial) is submitted to NIH AND the clinical trial begins on or after January 18, 2017.  (NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information in NIH Guide Notice NOT-OD-16-149).

For studies not funded by NIH, results must be submitted for most Applicable Clinical Trials (ACTs). Whether you need to submit results for an ACT depends on the Primary Completion Date – the date the last study subject had their last study visit for the purposes of data collection.

If you are not sure if your study is an Applicable Clinical Trial, this flowchart from the NIH could help. We also recommend reviewing Applicable Clinical Trial (ACT) PDF. More information can be found on the ClinicalTrials.gov FAQ.

January 18, 2017: Effective Date of Final Rule for Clinical Trials Registration and Results Information Submission (42 CFR Part 11)

Beginning January 1 2020, PRS will begin publicly posting results submitted to ClinicalTrials.gov within 30 days of the date submitted, and immediately after they complete their QC review, regardless of whether there are Major Issues with the submitted results.

Applicability

This applies ONLY to:

• Applicable Clinical Trials (ACTs)
• Initiated on/after January 18 2017
• For which results data is first submitted on or after January 1 2020

Non-ACTs, older studies, and studies for which results were submitted to PRS prior to 1/1/2020 will not have results released after QC review if there are Major Issues outstanding.

Public Records with QC Review Comments

Results published with Major Issues identified during the QC process will display a disclaimer that the QC review process has not completed, with a link to the Results section (as shown below).

The public results record will display the Major Issues identified in the record, but will not include the explanatory text for any of the comments (see below).

Corrections to Public Records with Comments

Results will be publicly posted immediately following QC review. You will not have a chance to correct Major Issues before they become part of the public record. Corrections to Major Issues will be expected within 25 days.

Previous public versions of a record are permanently accessible. If Major Issues are identified, make the required corrections to the record within the 25 Day time frame, or you may find yourself having to explain to journals or funders why the corrections were late.

NIH Definition: “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.”

Answer the following four questions to determine if your study is a clinical trial:

1. Does the study involve human participants?
2. Are the participants prospectively assigned to an intervention?
3. Is the study designed to evaluate the effect of the intervention on the participants?
4. Is the effect being evaluated a health-related biomedical or behavioral outcome?

If you answered yes to all 4 questions, your study would meet the NIH definition of a clinical trial. If you are still not sure, a decision tool can be found here: https://grants.nih.gov/ct-decision/index.htm

Your study is considered to meet the NIH definition of a clinical trial even if:

• Your study uses healthy participants, or does not include a comparison group (e.g., placebo or control)
• Your study is only designed to assess the pharmacokinetics, safety, and/or maximum tolerated dose of an investigational drug
• Your study utilizes a behavioral intervention
• Your study uses an intervention for the purposes of understanding fundamental aspects of a phenomenon (See guidance and FAQs about Basic Experimental Studies with Humans (BESH)). 

Your study is NOT considered to meet the NIH definition of a clinical trial if:

• Your study is intended solely to refine measures.
• Your study involves secondary research with biological specimens or health information.

Why does it matter? Correctly identifying if your study is a clinical trial, as defined by the NIH, is crucial to how you will:

• Comply with registration and reporting requirements in ClinicalTrials.gov
• Select the right NIH funding opportunity announcement for your research study
• Write the research strategy and human subjects sections or your grant application and contact proposal

If no participants were ever enrolled in the trial, open the Protocol section of the record, edit the Study Status section, and set the Overall Recruitment Status to “Withdrawn”. No further results information will need to be submitted.

For a trial that was terminated after participants were enrolled, provide any available data.

1. Click on "Open" next to "Results Section".
2. Click “Open” next to the Participant Flow, Baseline Characteristics, and Adverse Events modules, and submit the data for the enrolled participants for each.
3. Click "Open" next to "Outcome Measures".
4. Click "Edit" next to the desired Outcome Measure.
5. Click "Enter Outcome Measure Data" if prompted. Copy the arms/groups from Participant Flow or Baseline Characteristics, and click “Save” to save the Arms/Groups. This will take you to the Outcome Measure Data module.
6. If any data were collected for the Outcome Measures, enter the data. If no data are available for any of the Outcome Measures, enter “0” in the fields next to "Overall Number of Participants Analyzed".
7. Enter the reason data were not analyzed in the Analysis Population Description (e.g. “This trial was terminated early due to enrollment challenges. No data was collected or analyzed for this Outcome Measure.”)
8. Click “Save”.

If appropriate, also provide information about the limitations of the available data and the circumstances in the Limitations and Caveats module.

Online presentations and webinars on using the Protocol Registration and Results System (PRS) are available for free on ClinicalTrials.gov?

Browse to the Training Materials page to access recorded presentations and slides on topics such as:

• Overview of ClinicalTrials.gov and Related Policies
• Submitting Results Data
• The Final Rule (42 CFR Part 11) Requirements

PRS Guided Tutorials (currently in BETA testing)

No. If the trial is an applicable clinical trial (ACT) or probable ACT (pACT), results data must be entered in ClinicalTrials.gov in a tabular format. It is not sufficient to post the manuscript/publication/study report or PDF in lieu of this requirement. 

To point interested parties toward your publication, provide the unique PubMed Identifier (PMID) of the article or enter the full bibliographic citation in the Citations field in the protocol section) and PRS will add the link(s).

Examples of Good and Bad Individual Participant Data (IPD) Sharing Statements

Very Bad IPD Sharing Statement:

• Plan to Share IPD: “Undecided”

ICMJE data sharing recommendations state that “Undecided” is not an acceptable response for publication. If a plan is not yet in place, select “No” and change it later if you decide to share IPD.

Bad IPD Sharing Statement:

• Plan to Share IPD: “Yes”
• Plan Description: “No individual participant data will be shared. Results will be published by the investigators in academic journals. Sharing of generated study data will be carried out in several different ways. We plan to make our results available to researchers and potential collaborators interested in sickle cell anemia.”

The Plan to Share IPD element is “Yes”, but the plan description starts with “No IPD will be shared.” Aggregate data sharing (i.e. publication) should also not be included in the plan description.  Finally, the plan does not provide a time frame for when or how long the data will be made available, or how to request access.

Okay IPD Sharing Statement:

• Plan to Share IPD: “Yes”
• Plan Description: “Data obtained through this study may be provided to qualified researchers with academic interest in sickle cell anemia. Data or samples shared will be coded, with no PHI included. Approval of the request and execution of all applicable agreements (i.e. a material transfer agreement) are prerequisites to the sharing of data with the requesting party.

To make this a Good Sharing Statement, the record owner could add the following details:

• Time Frame: “Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.”
• Access Criteria: ““Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA).”

These tips were adapted from slides by Leah Silbert, Sr. Research Compliance Analyst at Cedars-Sinai Hospital, provided to the ClinicalTrials.gov Task Force on 3/21/2019.