ClinicalTrials.gov CWRU FAQs

Most frequently, registration with ClinicalTrials.gov is done to comply with regulatory and funding source obligations (see “Which studies require registration?” below). However, there are significant advantages in registering with ClinicalTrials.gov even when the regulations don’t specifically require it. 

• Journals can verify that manuscript authors have met their standards for publication.
  • Many journals will NOT publish results from an unregistered trial. 
• A public record of your study may assist in participant recruitment as patients and their health care providers look for research opportunities.
• Registration ensures transparency; study participants can see results from trials that they contributed to or benefitted from, researchers and scientists are able to readily find studies that they may use as a reference or to identify potential future collaborators, and the public is able to see the outcomes of tax dollar-subsidized trials.

The bullet points below represent the types of studies and circumstances that precipitate a requirement to register your study. 

• Applicable Clinical Trials (See "What is an Applicable Clinical Trial?")
• NIH-Defined Clinical Trials (See “What is an NIH-Defined Clinical Trial?”)
• WHO-Defined Clinical Trials (See “What is a WHO-Defined Clinical Trial?”)
• Studies a drug, biologic, or device
• Studies that bill insurance, including Medicare, Medicaid, and private insurance
• As required by the grant (will be listed in the funding/award agreement)
• Plan to publish in an ICMJE-affiliated journal or journals stating that they follow the ICMJE recommendations (See “What is the ICMJE?”)

For more information, refer to the CWRU ClinicalTrials.gov Registration Requirements or review additional guidance and resources on the CWRU ClinicalTrials.gov support page.

Note that the CWRU IRB performs ancillary reviews of all submissions to determine if the study meets federal and university requirements for ClinicalTrials.gov registration and results reporting.

All Applicable Clinical Trials (ACTs) are required to register on ClinicalTrials.gov. If all of the following bullet points are TRUE, your study is an ACT and must be registered:

• The study is interventional.
• At least one of the following applies:
  • .At least one study site is in the US or US Territory
  • Study is conducted under an Investigational New Drug application (IND) or Investigational Device Exemption (IDE).
  • The product being studied is manufactured in and exported from the US or US Territory.
• Evaluates at least one drug, biological, or device.
• Is NOT a Phase 1* or Early Feasibility study**

*A Phase 1 Drug Study is done to find the highest dose that can be given safely without causing severe side effects. 
**An Early Feasibility Device Study usually enrolls 10 or fewer people to test the safety and/or efficacy of the device; very specific criteria must be met to meet the EFS standard. Check with the FDA’s Early Feasibility Studies Program to see if your study meets this criteria.

For more information, refer to the CWRU ClinicalTrials.gov Registration Requirements or review additional guidance and resources on the CWRU ClinicalTrials.gov support page.

Studies that meet the definition of an NIH-Defined Clinical Trial are required to be registered on ClinicalTrials.gov. If all of the following bullet points are TRUE, your study is an NIH-Defined Clinical Trial and must be registered:

• One or more human subjects prospectively assigned to one or more interventions, including placebo or control groups/arms, to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.
• Grants submitted on or after 1/18/2017 OR grant renewals of a clinical trial initiated on or after 1/18/2017.
• Trials funded in whole or in part by U.S. Department of Health and Human Services (HHS) or other Common Rule Signatories.

For more information, refer to the CWRU ClinicalTrials.gov Registration Requirements or review additional guidance and resources on the CWRU ClinicalTrials.gov support page.

CWRU policies require ClinicalTrials.gov registration for studies that meet the World Health Organization’s definition of a clinical trial:

“A clinical trial 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. Clinical trials may also be referred to as interventional trials. Interventions include but are not restricted to drugs, cells and other biological products, surgical procedures, radiologic procedures, devices, behavioural treatments, process-of-care changes, preventive care, etc. This definition includes Phase I to Phase IV trials.”

For more information, refer to the CWRU ClinicalTrials.gov Registration Requirements or review additional guidance and resources on the CWRU ClinicalTrials.gov support page.

Also, see "What is the ICMJE?" below.

The International Committee of Medical Journal Editors (ICMJE), is a volunteer organization of medical journal editors who provide recommendations for the conduct, reporting, editing, and publication of medical journals. If a manuscript references a clinical trial, the ICMJE requires it to be publicly registered on ClinicalTrials.gov. Further, it requires prospective registration, meaning that the date of registration must predate the date that the first participant was enrolled.

The ICMJE follows the World Health Organization’s definition of a clinical trial: "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." This definition closely aligns with the NIH definition. While the ICMJE is made up of a small number of international medical journals, there are a very large number of journals and publications that follow the ICMJE requirements for prospective registration. Therefore, CWRU requires that all interventional studies register with ClinicalTrials.gov to ensure the widest range of publication opportunities.

There can be multiple consequences for failing to register or maintain a record or post results. These vary depending on the type of trial, funding source, and whether FDA oversight applies. 

Consequences may include:

• Federal civil money penalties of over $12,000 (USD) a day until the record is brought back into compliance. 
• Study funding may be clawed back and future funding to the investigator or the entire university may be refused. 
• Journals may decline publication of manuscripts related to studies that have no or incomplete records, or that did not follow the ICMJE guidelines for prospective registration. 

The “Responsible Party” is the person responsible for verifying the accuracy of a study record and releasing it for review and public posting. At CWRU, this person will most often be the principal investigator (PI). When your record is created, the Responsible Party defaults to “Sponsor,” which in our case is the sponsor organization of CWRU (CaseWestern). The university will remain the Responsible Party until the record is assigned its NCT, or National Clinical Trial number. Once assigned, the Responsible Party will become the PI. Please note that any fines incurred due to a lack of record maintenance or results reporting will be charged to the Responsible Party’s department.

Creating and maintaining your ClinicalTrials.gov record, also known as registration, is done through the ClinicalTrials.gov Public Registration System (PRS). Individual PRS accounts are set up under their specific sponsor’s account. For ClinicalTrials.gov, “sponsor” refers to the institution under which investigators perform their study activities or that is responsible for administering the grant or award. For CWRU, your account will be linked to the CaseWestern PRS organization name.

Please note that CWRU and UH, as well as other affiliate hospitals, have separate PRS organizational accounts. The approving IRB or institutional HRPP will help you determine which PRS under which to register your study. However, if your study is approved by the CWRU IRB or if your study’s funding is managed by CWRU, you will likely register your study with the CaseWestern PRS. If you do not already have an account, please e-mail irbqip@case.edu to request an account be created.

*Affiliate hospitals are: Cleveland Clinic, The MetroHealth System, University Hospitals, Louis Stokes Cleveland Veterans Affairs Medical Center.

Please email irbqip@case.edu to request an account be created for you and any study team members who will need access to the record.

Refer to the CWRU ClinicalTrials.gov Study Registration Guide for detailed instructions on creating a new record and completing the study template. Additionally, the PRS web page Protocol Registration Data Element Definitions provides comprehensive information on each required template field.

There are some basic considerations when creating a new record in ClinicalTrials.gov:

• The record can be created by anyone with a PRS account. This person automatically becomes the Record Owner. Note that once the record is posted, the Record Owner can be changed by your organization’s PRS administrators.
• On average, the record template takes roughly two to three hours to complete. It is recommended that you have your study’s IRB approved protocol, consent form, and other relevant documents on hand to reference during template completion.
• As you complete the record template, you will notice that required fields are marked with a red asterisk. You will not be able to complete registration if the required fields are left blank. We recommend completing non-required fields that apply to your study.
• When the template is complete and shows no errors or missing fields, the record is released for a quality control review performed by National Library of Medicine specialists. They review the record for errors, discrepancies, and adherence to the site’s formatting standards. See Protocol Registration Quality Control Review Criteria for information on the review process.
  • It is common for the record to be returned for further edits; a typical record is returned at least once for requested changes and often is returned multiple times.
• Once the Quality Control (QC) Reviewers are satisfied that the record meets their criteria, it is assigned a National Clinical Trial (NCT) number and posted on the public-facing ClinicalTrials.gov website.
• If the QC Reviewers identify major issues with the record, the Record Owner and Responsible Party have 15 calendar days in which to address the issues and re-release the record. For more information, see the question below: “My ClinicalTrials.gov record came back from PRS Review with Advisory Comments. How do I address these?” (See question below)

An important consideration at the registration stage: the more descriptive and clear your record’s Protocol Section is, especially the Arms and Outcomes subsections, the easier it will be to later enter results.

Registering your record in ClinicalTrials.gov should be done as soon as possible, even if you have not yet secured your CWRU IRB approval. However, it is helpful to know what the ACT, NIH, and ICMJE requirements are as regards the timing of registration:

• Applicable Clinical Trials must be registered no later than 21 days after enrollment of the first participant.
• NIH-Defined Clinical Trials must also be registered no later than 21 days after enrollment of the first participant.
• ICMJE “recommends that all medical journal editors require registration of clinical trials in a public trials registry at or before the time of first patient enrollment as a condition of consideration for publication.”

To ensure the broadest possible publication opportunities, CWRU strongly encourages study teams to register their records on ClinicalTrials.gov prior to the enrollment of participants.

Often, records do not meet the standards of the Quality Control Review and are returned for corrections. When major issues are identified, the record owner and Responsible Party receive notification from ClinicalTrials.gov; the CWRU PRS Administrators will also email you regarding these comments or any identified errors.

When a record has been identified with issues, it must be corrected and re-released within 15 calendar days. CWRU PRS Administrators are available to help with this process. Please email irbqip@case.edu to request assistance.

Once your record is registered and posted, it will need to be periodically edited and updated. Each record is required to provide a yearly update. Most often this will involve reviewing the record for accuracy and changing the record verification date. However, there are common circumstances that will require the record to be updated more frequently than yearly, including:

• If changes via a protocol modification affect human subjects (i.e., eligibility criteria, alteration of study arms or interventions), the information must be updated within 30 days of the IRB’s approval.
• The record must be updated within 30 days of any changes in recruitment status or completion of study.
• For studies funded by the NIH/Common Rule agencies, a copy of the most recent IRB-approved version of the study consent form will need to be uploaded to the record within 60 days of recruitment completion.
• The record must be updated within 15 days of change in approval or clearance status of drugs and devices not previously approved by FDA.
• ClinicalTrials.gov PRS Review Comments and Record Errors will need to be addressed and/or corrected within 15 days of the notification date.

Not all records registered on ClinicalTrials.gov are required to post results. Currently, results must be posted for the following studies:

• Applicable Clinical Trials
• NIH-Defined Clinical Trials
• As required by the terms of a funding agreement or contract

The ICMJE does not require results submission when the study does not meet the criteria listed above. However, they “expect authors to meet the results information submission requirements of their funding and regulatory agencies and encourage results reporting even when not required.” Similarly, CWRU encourages all investigators to submit results, even when not expressly required by federal regulations or the terms of their award or funding agreement.

Primary outcome results need to be submitted no later than 1 year after the trial’s Primary Completion date.

• Primary Completion Date: date that the final participant was examined or received an intervention for the purposes of final collection of data for the primary outcome(s).

All results, including secondary outcomes and adverse events, must be submitted no later than 1 year after the trial’s Study Completion date.

• Study Completion Date: 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 additional information on the difference between Primary and Study Completion Dates, see Protocol Registration Data Element Definitions.

Please note that the 1 year rule is absolutely non-negotiable. The National Library of Medicine may grant extensions to delay results posting in the event of emergencies, such as natural disasters, but will NOT grant an extension because you haven’t published a manuscript yet. Additionally, many journals have embargoes related to study information and publicity while a manuscript is under consideration or prior to publication. These embargoes DO NOT include ClinicalTrials.gov or other trial registries.

It is best to start preparing your study results as soon as possible to avoid having to rush at the last minute. To help you prepare for results entry, refer to the preparation checklists and templates offered in the section titled “How do I enter results for my ClinicalTrials.gov record?"

Entering results can begin as soon as you have posted an actual primary completion date. To do so, you will first need to make sure that your record is free from errors. Results cannot be entered if the record has any errors or advisory issues. A record with errors will be marked with a red flag.

The Results Section of the record contains six modules, detailed below.

• Participant Flow: The Participant Flow module is a tabular summary of participants’ progress through each stage of a study by assignment group, including the number of enrolled and randomized participants, arm allocation, and number of participants that completed each arm/intervention. More information can be found in the Participant Flow Data Preparation Checklist and Participant Flow Template.
• Baseline Characteristics: The Baseline Characteristics module is a tabular summary of data for each demographic and baseline measure by arm and for the entire population of participants. These include age, sex or gender, race and ethnicity, region of enrollment, and baseline measures. See the Baseline Characteristics Data Preparation Checklist and the Age, Sex/Gender, Race/Ethnicity/Region, and Study Specific Measure templates for detailed information on preparing and entering these characteristics.
• Outcome Measures: Outcome Measures is a summary of data, again in tabular form, for each pre-specified primary and secondary outcome measure. These are reported by arm or comparison group and include the statistical analysis that was pre-specified in the protocol and/or statistical analysis plan. You may also report other pre-specified and post hoc outcome measures in this section, as well as exploratory outcome measures as long as they are labeled as such in the protocol. Please note that if data was collected, it must be reported. See the Outcome Measure and Statistical Analysis Data Preparation Checklist and the Outcome Measure, Outcome Measure Examples, and Statistical Analysis templates for more information on reporting outcome measures.
• Adverse Events: This will include a summary of all anticipated and unanticipated events collected during the study. Adverse events are reported in tabular format as All-Cause Mortality, Serious Adverse Events, and Other Adverse Events. See the Adverse Events Data Preparation Checklist and Serious Adverse Events and Other Adverse Events templates for more information on how to classify and enter your adverse event results.
• Limitations and Caveats: If your study experienced significant limitations—such as not reaching enrollment targets, leading to an inability to achieve target power and statistically reliable results—that type of information would be entered here. See the Results Data Element Definitions web page and Entering Limitations and Caveats guided tutorial.
• More Information: Certain Agreements and Results Point of Contact: This section is a combination of two modules where you will enter (a) information regarding any agreements between sponsors and PIs that may limit the PI’s ability to publish or discuss results and (b) who to contact regarding the study result’s scientific information. See the Certain Agreements and Results Point of Contact tutorial and Results Data Element Definitions web page.

All studies that are required to report results in their record must upload a PDF copy of the protocol and statistical analysis plan at the time of results submission. For NIH-Defined Clinical Trials, a copy of the current, IRB-approved consent form must be uploaded within 60 days of the study’s Primary Completion Date. See the Uploading Study Documents tutorial, Results Data Element Definitions web page, and HHS’ Informed Consent Posting Instructions for more information.