Support for Clinical Trials Registration & Results Reporting
ClinicalTrials.gov 101 Session Slides
Registration Requirements for ClinicalTrials.gov
There are two distinct entities that require Primary Investigators (PIs) to register their studies on ClinicalTrials.gov (CT.gov): The Food and Drug Administration (FDA), and the International Committee of Medical Journal Editors (ICMJE). FDA and ICMJE have very different criteria for determining which studies must be registered on CT.gov, and it is important to carefully review the criteria that your study might fall under: PIs submitting their study to the HS/MR IRBs need to look at both FDA and ICMJE, and PIs using the ED/SBS IRB only need to look at ICMJE.
If you have questions about the application of the FDA and/or ICMJE registration requirements, please contact CT.gov Support using the information at the bottom of this page.
Additionally, the Center for Medicare & Medicaid Services (CMS) requires the registration of most studies billing third parties for study related services. For more information on the CMS requirements, contact Nancy Lutz, UW Health Research Compliance Billing Program at firstname.lastname@example.org.
FDA Requirements for Registration
The FDA requires study registration along with results and adverse event reporting for all phase II - IV interventional drug, biologic or device trials ("applicable clinical trials"). This is a legal requirement (FDAAA 801); failing to register or report results for "applicable clinical trials" in a timely manner can result in civil and significant monetary penalties.
Drug Trials: A study involving drugs (including biological products) is an “applicable clinical trial” if the following four criteria are met: (1) the study is a controlled; (2) clinical investigation; (3) other than a Phase I clinical investigation; (4) of a drug subject to section 505 of the Federal Food, Drug, and Cosmetic Act (FDC Act) or section 351 of the Public Health Service Act (PHS Act).
- Controlled: An investigation is considered controlled if it is designed to permit a comparison of a test intervention with a control to provide a quantitative assessment of the drug effect. Controls included placebo concurrent control, does-comparison control, no intervention concurrent control, active intervention concurrent control, and historical control.
- A clinical investigation: A clinical investigation is “any experiment in which a drug is administered or dispensed to, or used involving, one or more human subjects.” This includes studies that in which subjects are assigned to specific interventions according to a study protocol, but would not include use of a marketed drug in the course of medical practice.
- Other than a Phase I clinical investigation: Phase I studies include the initial introduction of an investigational new drug into humans. The total number of subjects in Phase I studies may vary, but generally range from 20 to 80. Phase I studies are designed to determine metabolism and pharmacologic actions of the drugs in humans.
- A drug subject to section 505 of the FDC Act or section 351 of the PHS Act: A drug or biologic is considered subject to sections 505 or 351 if it is the subject of an approved new drug application (NDA) or biologics license application (BLA) OR if an approved NDA or BLA would be required in order for that drug or biologic to be legally marketed. Drugs being studied under an Investigational new drug application (IND) are considered subject to section 505. Drugs being studied in a clinical investigation can be the subject of section 505 or 351 even if the clinical investigation of that drug does not require an IND (e.g., falls within 21 CFR § 312.2(b)). This would include the investigation of drugs outside of their FDA approved indications.
Device Trials: A study involving a device is an “applicable clinical trial” if the following four criteria are met: (1) it is a prospective clinical study of health outcomes; (2) it compares an intervention with a device against a control in human subjects; (3) the studied device is subject to section 510(k), 515, or 520(m) of the Federal Food, Drug, and Cosmetic Act (FDA Act); and (4) it is other than a small clinical trial to determine the feasibility of a device, or a clinical trial to test prototype devices where the primary outcome measure relates to feasibility and not health outcomes. Additionally, a study involving a device is an “applicable clinical trial” if it is a pediatric post-market surveillance of a device as required under section 522 of the FDC Act
- A prospective clinical study of health outcomes: A study is “prospective” if it is not retrospective or, in other words, is one in which subjects are followed forward in time from a well-defined point. A “clinical study” of a device is any experiment in which a device is administered, dispensed to, or used involving one or more human subjects. The definition of a clinical study of a device would include studies in which subjects are assigned to a specific intervention in a clinical investigation according to a study protocol. A study involves “health outcomes” if the primary purpose is to evaluated a defined clinical outcome directly related to human health (e.g., evaluate the ability of a device to make a diagnosis of a disease or affect a particular condition).
- Comparing an intervention with a device against a control in human subjects: This criterion is met when a study compares differences in clinical outcomes (or diagnoses) between subjects who received an intervention that included a device and control subjects (who received other interventions or no intervention). The intervention may be with a device that has never been cleared or approved, or with an already marketed device whether or not the device has been cleared or approved for the indication being studied.
- A device subject to section 510(k), 515, or 520(m) of the Federal Food, Drug, and Cosmetic Act: A device (including significant risk devices requiring an investigational device exemption (IDE); a non-significant risk device that is considered to have an approved IDE; or a device that is exempt from submission requirements) is subject to section 510(k), 515, or 520(m) of the FDC Act if any of the following is required before it may be legally marketed: (1) a finding of substantial equivalence under section 510(k) permitting the device to be marketed; (2) an order under section 515 of the FDC Act approving a premarket approval application for the device; or (3) a humanitarian device exemption under section 520(m) of the FDC Act.
- Other Than a Small Clinical Trial to Determine the Feasibility of a Device, or a Clinical Trial to Test Prototype Devices Where the Primary Outcome Measure Relates to Feasibility and Not to Health Outcomes: Studies designed primarily to determine the feasibility of a device or to test a prototype device are considered to be trials conducted to confirm the design and operating specifications of a device before beginning a full clinical trial. Feasibility studies are sometimes referred to as Phase 1 studies, pilot studies, prototype studies, or introductory trials. Feasibility studies are not considered applicable device clinical trials under the statutory definition.
For additional information on the FDA's registration requirements, please download the National Institutes of Health's Elaborations of Definitions of Responsible Party and Applicable Clinical Trial.
ICMJE Requirements for Registration
ICMJE requires study registration in a public trials registry as a condition of publishing in many peer-reviewed medical journals, including JAMA, NEJM, Annals of Internal Medicine, Lancet, etc. A study requires registration for ICMJE purposes if the following three criteria are met: (1) prospective assignment; (2) to a health-related intervention; (3) to study the cause-and-effect relationship between a health-related intervention and a health outcome.
Publication of interventional health outcome studies in journals adhering to the ICMJE Uniform Requirements for Manuscripts Submitted to Biomedical Journals is contingent on timely study registration. The ICMJE does not currently require results reporting.
- Prospective assignment: A study is “prospective” if it is not retrospective or, in other words, is one in which subjects are followed forward in time from a well-defined point.
- A health related intervention: Health related interventions are those activities used to modify a biomedical or health-related outcome. Examples include drugs, surgical procedures, devices, behavioral treatments, educational programs, dietary interventions; quality improvement interventions, and process-of-care changes.
- To study the cause-and-effect relationship between a health-related intervention and a health outcome: Health outcomes are any biomedical or health-related measures obtained in subjects, including pharmacokinetic measures and adverse events.
For additional information on the ICMJE's registration requirements, please visit the ICMJE's Clinical Trials Registration website.
If your study receives NIH funding:
Please review the ICMJE registration criteria above. If your study meets this criteria, and is in part or fully funded by the NIH, you are now required to register on ClinicalTrials.gov. Additional NIH study obligations include placing a statement about ClinicalTrials.gov in your consent form and results reporting on CT.gov shortly after the end of the study's treatment phase. More information on the NIH's new requirements can be found on their website.
Who is responsible for trial registration?
The study sponsor is generally responsible for trial registration and the sponsor must register all industry-sponsored trials.
However, the UW-Madison investigator is responsible for registration when one or more of the below conditions are met:
- The trial is initiated by a UW-Madison investigator
- The trial is a federally sponsored and UW-Madison is the only study site OR the study's coordinating center
- The UW-Madison investigator is the holder of an Investigational New Drug (IND) application for the agent being studied OR the IRB has determined that the agent being studied is IND exempt
- The UW-Madison investigator is the holder of an Investigational Device Exemption (IDE) for the device being studied OR the IRB has made a non-significant risk (NSR) determination for the device being studied
For additional information on the responsibility for trial registration, please download the National Institutes of Health's Elaborations of Definitions of Responsible Party and Applicable Clinical Trial.
When do you need to register your trial?
The FDA requires that all "applicable clinical trials" be registered within 21 days of the first subject's enrollment. The ICMJE requires trials to be registered prior to the first subject's enrollment.
However, the ClinicalTrials.gov registration process can involve multiple rounds of quality assurance comments from the ClinicalTrials.gov staff, so UW-Madison recommends beginning the registration process as soon as your study has been approved by the IRB. For additional information on the quality assurance review process, please download the FDA's ClinicalTrials.gov Protocol Review Criteria.
Creating, Updating, and Reporting Results for Your ClinicalTrials.gov Record
Creating Your ClinicalTrials.gov Account
The University of Wisconsin is registered as an institution at ClinicalTrials.gov and has appointed ClinicalTrials.gov administrators to assist UW-Madison investigators or their designees in establishing their ClinicalTrials.gov accounts. To request a user login, send an email message to your assigned ClinicalTrials.gov administrator (see below) with your name, department, email address, and telephone number. You will then receive an email with a login name and a temporary password that will allow you to register your protocol.
For cancer-related protocols, contact:
- UW Comprehensive Cancer Center Clinical Trials Reporting Team at CTReporting@uwcarbone.wisc.edu
For all other protocols, contact:
- CT.gov Support, Office of Research Compliance (608) 890-1241 or ClinicalTrials.gov_Support@research.wisc.edu
Creating Your ClinicalTrials.gov Record
For a step-by-step explanation of how to register your study, visit ClinicalTrials.gov's website on How to Register Your Study. And for an explanation of the data fields within ClinicalTrials.gov, visit ClinicalTrials.gov's website on Data Elements Definitions.
Please complete the below data elements within ClinicalTrials.gov, as follows:
- Unique Protocol ID: [Your UW IRB protocol number]
- Responsible Party: "Sponsor"
- Sponsor: "University of Wisconsin, Madison"
- Owner: [Study PI]
- Access List: [All other study team members who will be working with the CT.gov record]
Updating Your ClinicalTrials.gov Record
Once your trial is registered, the FDA requires that your ClinicalTrials.gov record be updated within 30 days of a change in recruitment status or completion date. Additionally, your Record Verification Date needs to be updated at least every 12 months and updated with any protocol changes that have occurred since your last update. For a further explanation of how to update your record, visit ClinicalTrials.gov's website on How to Edit Your Study Record.
Reporting Results for Your ClinicalTrials.gov Record: Results reporting is only required for studies that meet the FDA registration requirements ("applicable clinical trials"). Results should not be reported when only the ICMJE registration requirements apply.
ClinicalTrials.gov has four results reporting modules:
For a step-by-step explanation of how to report results, visit ClinicalTrials.gov's website on How to Submit Your Results. ClinicalTrials.gov also provides a very helpful Pre-Submission Checklist for results reporting.
When do you need to report results for your trial?: The FDA requires that the results of "applicable clinical trials" be reported within 12 months of the last subject's last study visit, which should be listed in ClinicalTrials.gov as the study's "primary completion date." Failing to properly update the "primary completion date" during the study may lead the FDA to believe that results should be posted before the study is actually completed. For additional information on the "primary completion date" within in ClinicalTrials.gov, please see ClinicalTrials.gov Data Element Definitions.
For questions concerning this website or clinical trials registration at UW-Madison, please contact:
CT.gov Support, Office of Research Compliance at (608) 890-1241 or ClinicalTrials.gov_Support@research.wisc.edu
Keywords: ClinicalTrials.gov, "study registration", "trial registration", FDA, ICMJE, "results registration", NIH, NCT, "NCT Number", "NCT ID", database