Clinicaltrials.gov

Below are the template language for NIH Clinical Trials:

NEW COMPETING CLINICAL TRIALS:
(New applications submitted on or after January 18, 2017)

• ClinicalTrials.gov (must include this heading)

The proposed project will require registration in ClinicalTrials.gov.  Registration information will be submitted within 21 days of enrollment of the first subject and summary results information will be reported within one year of the primary completion date. 

• (Add to the Budget Justification section for new or competing applications submitted on or after January 18, 2017)
  
  ClinicalTrials.gov ($3,500)
  
  $3500 is requested for the support needed to facilitate the registration, periodic updates, and results reporting within ClinicalTrials.gov for the duration of the study.

PROGRESS REPORTS ON NIH CLINICAL TRIALS:
(New or competing applications submitted on or after January 18, 2017)

• ClinicalTrials.gov (must include this heading)

The following project is registered in ClinicalTrials.gov:  Insert ClinicalTrials.gov registry number (NCT#), the brief title listed in ClinicalTrials.gov, and the responsible party’s name, organization, and email address.

• To determine applicability of ClinicalTrials.gov requirements and/or to request registration of a study, please contact OCR@emory.edu.
• Review each record at least every 6 months to ensure accuracy and verify all information is up to date.
• Change the record verification date with each log in and "Release" by the Responsible Party.
• Keep information up-to-date by changing the PI, Owner, study status, etc., when needed.
• Responsible Parties should update their records within 30 days of a change see list by clicking on the link provided here: ClinicalTrials.gov FAQ - Updates to Clinical Trial Information
• Transition the study to another faculty member or close the trial in ClinicalTrials.gov prior to leaving Emory University.
• IND/IDE studies may only be registered by the IND/IDE holder. If the study is subject to FDA regulations, under an Investigational New Drug (IND) Application or Investigational Device Exemption (IDE), ensure that you are considered the Sponsor under your organization and are the IND/IDE holder before registering the study.
• For NIH-funded studies wherein the overall Sponsor is the NIH, coordinate with the relevant Institute or Center. If a study is a National Institutes of Health (NIH) funded study, registration should be coordinated with the sponsoring NIH Institute or Center to avoid duplicate registration. However, the NIH may designate the PI as the Responsible Party for specific grants held by the PI with the institution as the site.
• Multi-site studies are NOT registered by individual sites. If this is a multi-site study, it must be registered only once by the Sponsor (primary organization or industry entity that oversees implementation of study and is responsible for data analysis) or the designated principal investigator (PI).
• Coordinate with all collaborators before registering as the Sponsor. If the study has multiple collaborators, contact the other organizations to confirm that the study has not already been registered and to notify them that your organization, as Sponsor or as the designated PI, is registering the study. 

In order to facilitate compliance and ensure timely response to questions relating to ClinicalTrials.gov records, an Escalation policy is applicable for responding to emails from Emory’s OCR to investigators relating to ClinicalTrials.gov. This policy applies to Principal Investigators of investigator-initiated, Emory-Sponsored clinical trials registered in ClinicalTrials.gov where the PI is the IND or IDE holder, the clinical trial follows the NIH policy for ClinicalTrials.gov, and/or the study meets the criteria for International Committee of Medical Journal Editors (ICMJE) requirements. The policy for escalation can be found here: ClinicalTrials.gov Escalation and Enforcement Procedure.

• Continuing Education Opportunities
  • ClinicalTrials.Gov Three Part Series

• Information regarding the Final Rule & the NIH Policy are available at:
  • Clinical Trials Registration and Results Information Submission
  • HHS takes steps to provide more information about clinical trials to the public

• Information regarding the FDA Final Rule and FDA Applicable Clinical Trials is available at:
  • FDAAA 801 and the Final Rule
  • Checklist for Evaluating Whether a Clinical Trial or Study is an Applicable Clinical Trial (ACT) [PDF]
• Information regarding NIH clinical trial determinations can be found at the following locations:
  • Decision Tree for NIH Clinical Trial Definition (PDF)
  • Clinical Trial Requirements for Grants and Contracts

Information regarding the International Committee of Journal Editors requirements can be found at the following locations:

• ICMJE Clinical Trials Registration FAQs
• The list of journals following ICMJE requirements
• Data Element Definitions, Templates, & Checklists
• ClinicalTrials.gov Frequently Asked Questions

The Responsible Party for a clinical trial must register the trial and submit results information. The Responsible Party is defined as:

• The Sponsor of the clinical trial (e.g., Industry Sponsor, Federal Sponsor, or Investigator-initiated);

or

• The Principal investigator (PI) of a clinical trial if an Investigator-initiated study or if designated by a sponsor, grantee, contractor, or awardee, so long as the PI is responsible for conducting the trial, has access to and control over the data from the clinical trial, has the right to publish the results of the trial, and has the ability to meet all of FDAAA's requirements for the submission of clinical trial information.

Note:  For Emory Investigator-initiated studies, OCR is willing to assist with determining if ClinicalTrials.gov registration is necessary. Emory OCR will also assist with entering and updating the information in the ClinicalTrials.gov on behalf of the study team. Please contact OCR at either ocr@emory.edu or 404-778-4960 for questions, etc.

The "Responsible Party", or Sponsor, for a clinical research trial must register and "Approve/Release" the trial on ClinicalTrials.gov. This includes clinical trials in which an Emory Investigator is the Primary (i.e., Lead) Investigator for the overall study (e.g., investigator-initiated trials that are multi-center) where Emory is in control of all data need to be registered in ClinicalTrials.gov by the Emory Investigator.  ClinicalTrials.gov registration is not completed by site Principal Investigators for clinical trials that are managed by other sponsors or institutions, such as industry-sponsored studies. If a study is being conducted at multiple institutions, the Lead or Primary Investigator should register the trial.

It is the PI's responsibility to ensure that Emory-Sponsored clinical trial registration in ClinicalTrials.gov meets the requirements of applicable laws and regulations. Acceptance by ClinicalTrials.gov and assignment of an NCT number to a registration record does not ensure compliance with applicable laws – the study record must be maintained and accurate throughout the course of the research study and the Responsible Party (PI) needs to ensure the accuracy of the study record in ClinicalTrials.gov prior to releasing the information to NIH reviewers at ClinicalTrials.gov each time it is submitted. However, Emory will be assisting the study team with registration of the study, updating the study record for amendment changes, maintaining all other required updates as required by federal law, and results reporting, as applicable.

Additionally, while most Industry-Sponsored studies are registered by the Industry-Sponsor, it is the Emory Site PI's responsibility to ensure that trials conducted at Emory are registered with complete information in ClinicalTrials.gov. For background reading, see NEJM editorial Salvation by Registration, January 2007.

If a research study meets any one of the following definitions, the trial must be registered on ClinicalTrials.gov:

• The Food and Drug Administration (FDA) requires registration for "Applicable Clinical Trials" (ACTs) defined as follows:
  • For any trials of drugs and biologics: Controlled clinical investigations, other than Phase I investigations, of a product subject to FDA regulation.
  • For trials of biomedical devices: 1) Controlled trials with health outcomes of devices subject to FDA regulation, other than small feasibility studies, and 2) pediatric post-market surveillance required by FDA.

"Applicable clinical trials" generally include interventional studies (with one or more arms) of FDA-regulated drugs, biological products, or devices that meet one of the following conditions:

• The trial has one or more sites in the United States.
• The trial is conducted under an FDA investigational new drug application or investigational device exemption.
• The trial involves a drug, biologic, or device that is manufactured in the United States or its territories and is exported for research.

For more information on the definition of an "Applicable Clinical Trial," see Elaboration of Definitions of Responsible Party and Applicable Clinical Trial (PDF) and the Checklist and Elaboration for Evaluating Whether a Clinical Trial or Study is an Applicable Clinical Trial (PDF).

Note: If you are the Investigator of a Phase I Clinical Trial that has Emory HealthCare billable items and services, the study must be registered in ClinicalTrials.gov in order to obtain a NCT number (ClinicalTrials.gov Identifier). The NCT number is required for the processing of Medicare Reimbursement Claims.

• The National Institutes of Health (NIH) requires registration and results reporting for all clinical trials that meet the following definition: A research study¹ in which one or more human subjects² are prospectively assigned³ 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 outcomes⁵.

¹See Common Rule definition of “research” at 45 CFR 46.102(d)

²See Common Rule definition of “human subject” at 45 CFR 46.102(f)

³The term “prospectively assigned” refers to a pre-defined process (e.g., randomization) specified in an approved protocol that stipulates the assignment of research subjects (individually or in clusters) to one or more arms (e.g., intervention, placebo, or other control) of a clinical trial.

⁴An “intervention” is defined as a manipulation of the subject of subject’s environment for the purpose of modifying one or more health-related biomedical or behavioral processes and/or endpoints.  Examples include:  drugs/small molecules/compounds; biologics; devices; procedures; (e.g., surgical techniques); delivery systems (e.g., telemedicine, face-to-face interviews); strategies to change health-related behavior (e.g., diet, cognitive therapy, exercise, development of new habits); treatment strategies; prevention strategies; and, diagnostic strategies.

⁵A “health-related biomedical or behavioral outcome” is defined as the pre-specified goal(s) or condition(s) that reflect the effect of one or more interventions on human subjects’ biomedical or behavioral status or quality of life.”  Examples include:  positive or negative changes to psychological or neurodevelopmental parameters (e.g., mood management intervention for smokers; reading comprehension and/or information retention); positive or negative changes to disease processes; positive or negative changes to health-related behaviors’ and, positive or negative changes to quality of live.)

Revised Version Issued October 23, 2014

Note:  Clinical trial determinations for studies that are NIH-funded (in whole or part) should only be made by the NIH. Emory University will not make determinations for these studies. Please contact your NIHProgram Officer to confirm the determination and if ClinicalTrials.gov is required, if applicable.

• International Committee of Medical Journal Editors (ICMJE) defines a clinical trial as: 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.

In all cases, if you are uncertain whether or not your study meets the definition of a clinical trial, it is recommended to err on the side of registration.

Please note that when you register a research study with ClinicalTrials.gov, you will be responsible for completing the entry and updating the information throughout the course of the trial. Emory’s OCR will facilitate and assist with the process.

At a glance – Scope & Applicability:

The NIH reviewers at ClinicalTrials.gov will review the study record after it has been "Approved" and "Released" (a 2-step process required for submission of the record) by the Responsible Party, and before it is published on ClinicalTrials.gov. This review will focus on apparent validity (when possible), meaningful entries, logic and internal consistency, and formatting. Please note that the review process may take up to a few days. Ensuring that the record is consistent with the ClinicalTrials.gov protocol review criteria (PDF) before releasing it will expedite publication on the site.

After you release a record and it is accepted by review staff for publication, the record, including its NCT Number (ClinicalTrials.gov Identifier), will be available on the public ClinicalTrials.gov website within 2–5 business days. An email notification with the NCT Number is sent by ClinicalTrials.gov to the "Responsible Party" and "Owner" which includes this information.

Note: After initial review by ClinicalTrials.gov staff, some studies may require a response to "QA Review Comments" prior to the NCT number being assigned and the study being posted to the public website. The study team must address the comments made by ClinicalTrials.gov to move the process forward. Emory OCR will assist the study team with responding to all QA Review Comments.

The PI for a study must submit required clinical trial information and receive the NCT number prior to enrollment of the first participant to meet the International Committee of Medical Journal Editors (ICMJE) requirements for publication. Both the FDA Final Rule and NIH policy for ClinicalTrials.gov require registration within 21 days of enrollment of the first participant. In order to meet the requirements for publication under ICMJE, it is highly recommended to register a study in ClinicalTrials.gov prior to enrollment.

FDA:

Penalties under the FDA regulations for ClinicalTrials.gov non-compliance can include judicial remedies for violations and include injunctions and criminal penalties by the FDA and DOJ. The failure to submit clinical trial information, including the submission of any false or misleading information or a failure to correct a violation within a 30-day period following notification, will result in civil monetary penalties for Responsible Parties that can range up to $12,103 per day. Further, non-compliant study records will be noted publicly in ClinicalTrials.gov. For more information: ClinicalTrials.gov FAQ - Compliance.

NIH:

For federally-funded, NIH-defined clinical trials, penalties may include suspension or termination of grant or contract funding to the PI and/or the Institution. Non-compliance may impact future funding decisions to the PI and/or institution by the NIH. Further, non-compliant study records will be noted publicly in ClinicalTrials.gov.

ICMJE

Failure to register may result in the inability to publish the results of the trial in an ICMJE-associated journal. Those who are uncertain whether their trial meets the expanded ICMJE definition should err on the side of registration if they wish to seek publication in an ICMJE journal.

List of journals currently following ICMJE guidelines

The PRS Administrator for Emory University is the Office for Clinical Research (OCR). As part of Emory’s OCR Service Center for ClinicalTrials.gov, OCR assists investigators with the following in ClinicalTrials.gov:

• Establishing user accounts and temporary password;
• Assist with registration of studies;
• Resetting a password when the original is lost or forgotten;
• Updating study records for protocol amendment changes, status changes, etc.;
• Assist with required results reporting;
• Changing ownership of a study;
• Assist with resolving "problems" in ClinicalTrials.gov and ensuring maintenance of information reflective of current study status;
• Transferring a study to another institution or from another institution or from another institution.

To request assistance with any of the above items, contact OCR at ocr@emory.edu.

Note: OCR is not responsible for reviewing the content of information posted on ClinicalTrials.gov, ensuring accuracy of the study information on ClinicalTrials.gov, or submitting an application. This is the responsibility of the PI as the "Responsible Party" for the ClinicalTrials.gov study record.

• Informed Consent – Regulations require a statement be included in the informed consent for FDA Applicable Clinical Trials and NIH-funded, NIH clinical trials regarding the availability of clinical trial information on ClinicalTrials.gov. The statement is: "A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. This website will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this website at any time." CFR - Code of Federal Regulations Title 21. Emory University’s Institutional Review Board (IRB) has a sample Informed Consent template that provides the required language about ClinicalTrials.gov. Please visit their web page for additional information. IRB Forms

• Revised Common Rule and Posting of Clinical Trial Consent Forms - A revised Federal Policy for the Protection of Human Subjects, known as the "Common Rule" was issued in 2017 and became effective on July 19, 2018. The revised Common Rule requires that for any clinical trial conducted or supported by a Common Rule department or agency, one consent form used in enrolling participants be posted on a publicly available Federal website within a specific time frame. If a study is a NIH-funded clinical trials and registered in Emory’s ClinicalTrials.gov, "the informed consent form must be posted on the Federal website (e.g., ClinicalTrials.gov) after the clinical trial is closed to recruitment, and no later than 60 days after the last study visit by any subject, as required by the protocol" to meet the requirements of the Common Rule.

• Medicare payment– The Centers for Medicare & Medicaid Services (CMS) requires the NCT number (ClinicalTrials.gov Identifier) on Medicare claims associated with clinical trial participation. Clinical trial related claims submitted to Medicare for dates of services on or after January 1, 2014, will be rejected and returned to the provider if the NCT number is not present.

Emory University, Office for Clinical Research (OCR) requires research coordinators to provide the NCT Number to our office, upon request, in order to ensure research billing compliance for routine care (standard of care) items and services related to clinical trial participation.

Some data elements such as Start Date, Recruitment Status, and Completion Date are required to be updated within 30 calendar days of a change in status. Details can be found here: ClinicalTrials.gov FAQ - Updates to Clinical Trial Information. In general, clinical trial information in the study record must be updated at least every 12 months.

It is recommended that the Record Verification Date and information in the record be verified by the Responsible Party at least every 6 months for studies that are not yet completed, even if there were no changes to the record.

For responding to QA review comments from NIH reviewers at ClinicalTrials.gov after review of the record, corrections are required within 15 days for comments received during the registration process. Responses are required within 25 days for comments received during the results reporting review process for errors, deficiencies, and/or inconsistencies.

Under the FDA Final Rule, results of an Applicable Clinical Trial of a drug, biologic, or device that is approved, licensed, or cleared by the FDA must be submitted by the Responsible Party no later than 12 months after the Completion Date of the study. The timelines for Clinical Trial results information deadlines can be found at: ClinicalTrials.gov FAQ - When is required clinical trial results information due.

Per the complementary NIH policy, results for NIH-funded clinical trials are also required to report results no later than 12 months after the Completion Date for both primary and secondary study outcomes. More information can be found here regarding the deadlines for results: ClinicalTrials.gov FAQ - results due for ACT

At a glance – Deadline for Summary Results Reporting:

Delayed Submission of Results

Certification - A Responsible Party may delay submission of results, until the deadline described below, by submitting a certification (see note) that an Applicable Clinical Trial meets following conditions:

• If the responsible party is seeking approval, licensure, or clearance of a new use being studied for a product that previously has been approved, licensed, or cleared by the FDA.
• For applicable clinical trials with a Primary Completion Date on or after January 18, 2017, the Final Rule also provides for the delayed submission of results information under certain conditions with certification if the responsible party is seeking initial approval, licensure, or clearance for the studied product. The deadline for the delayed submission of results information is 30 calendar days after the earliest of specific events described in each provision, with a maximum deadline for delayed results information submission of 2 years after the date of submission of the certification.

Note: If a Responsible Party, who is both the sponsor and manufacturer, submits a new use certification this certification must be made with respect to each Applicable Clinical Trial that is required to be submitted in an application or report for licensure, approval, or clearance of the use studied in the clinical trial.

Extension Request

 An extension for good cause may be requested under certain circumstances to extend the deadline for submission of results information for an Applicable Clinical Trial. The Responsible Party is required to submit a written request within the ClinicalTrials.gov record that demonstrates good cause for the extension and provides an estimate of the date on which the results information will be submitted. Pending publication is not considered good cause for an extension.

Submitting a Certification or Request for Extension for Delayed Submission of Results

A certification or request for extension is submitted via the Protocol Registration System (PRS) within the study record. Submission of this certification will facilitate automated identification of trials that are not yet required to submit results if approval by the NIH at ClinicalTrials.gov is granted for the delay.

For questions regarding summary results reporting and/or requesting delayed results, please contact OCR directly for guidance at: ocr@emory.edu

How can someone volunteer for a registered clinical trial at Emory?

Please visit the webpage Clinical Trials at Emory.

• For more detailed information about ClinicalTrials.gov in general, please find instructions for Researchers at the following link: ClinicalTrials.gov Support Materials

• For questions about a specific study, to include clinical trial determinations, ClinicalTrials.gov applicability, etc., please contact OCR directly for guidance at: ocr@emory.edu or 404-778-4960.