Guidelines for Registering with ClinicalTrials.gov

What is ClinicalTrials.gov?
Department of Health and Human Services (DHHS) Regulation
National Institutes of Health (NIH) Policy
What is the Specific Wording Required in the UCI Consent Form?
Creating a profile on ClinicalTrials.gov

What is ClinicalTrials.gov?

ClinicalTrials.gov is a publicly available registry and results database of federally and privately supported clinical trials conducted in the United States and around the world. The purpose of ClinicalTrials.gov is to disclose to the public key information about clinical trials that are currently available or that have been conducted. ClinicalTrials.gov captures significant summary protocol information before and during the trial as well as summary results and adverse event information of a completed trial. Federal laws and regulations as well as editors of prominent medical journals require registration of a clinical trial, as described below.

Department of Health and Human Services (DHHS) Regulation for Clinical Trials Registration and Results Information Submission – Final Rule

DHHS Required Registration and Reporting:

The Food and Drug Administration Amendments Act (FDAAA) established legal requirements for sponsors and designated principal investigators (i.e., responsible parties) to report specified clinical trial information for certain applicable clinical trials to ClinicalTrials.gov.

In addition to registration, the statute established a system and mandate for reporting summary results information within certain time frames, independent of decisions about journal publication.

The FDAAA’s registration requirements are designed to provide potential participants with information about trials of interest. The registration requirements also serve to enable funders and others to determine the need for new trials; provide a more complete listing of clinical trials to inform the medical evidence base; and enable the scientific community to examine the overall state of clinical research as a basis for engaging in quality-improvement efforts (e.g., with regard to research methods).

What Does the DHHS Final Rule Mean to Researchers at UCI?

UCI Researchers who are considered the ‘Responsible Party’ are required to register their clinical trial with Clinicaltrials.gov if their study meets the definition of an Applicable Clinical Trial – or ACT. In addition to the initial registration, the Responsible Party must update the registration as applicable and within the necessary timeframe. For more specific information, please review the below table and visit www.clinicaltrials.gov.

Table 1: Key Elements of the DHHS Final Rule

Effective Date	January 18, 2017 Compliance date is April 18, 2017
Responsible Party to register study and study-results to ClinicalTrials.gov	The responsible party is considered to be the study sponsor (i.e., IND or IDE holder or the initiator of the study, considered the grantee organization for NIH-funded trials) or a sponsor-designated PI who is responsible for conducting the study, and has access to and control over the clinical data to analyze the data and publish the results. NOTE: Being unfunded does not exclude applicable clinical trials (ACTs) from the requirement to register.
Applicable Clinical Trials (ACT)	Applicable Device Clinical Trial Definition: (1) A prospective clinical study of health outcomes comparing an intervention with a device [21 U.S.C. 321(h)] product subject to section 510(k), 515, or 520(m) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 360(k), 21 U.S.C. 360e, 21 U.S.C. 360j(m)) against a control in human subjects (other than a small clinical trial to determine the feasibility of a device product, or a clinical trial to test prototype device products where the primary outcome measure relates to feasibility and not to health outcomes); (2) a pediatric postmarket surveillance of a device product as required under section 522 of the FD&C Act (21 U.S.C. 3601); or (3) a clinical trial of a combination product with a device primary mode of action under 21 CFR Part 3, provided that it meets all other criteria of the definition under this part. [Source: 42 CFR 11.10(a); 81 FR 65139] Criteria: The study is a pediatric postmarket surveillance of a device product as required by FDA under section 522 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 3601) OR The study is a clinical trial with one or more arms that meets all of the following criteria: Study type is interventional Primary purpose of the clinical trial is other than a feasibility study The clinical trial studies a U.S. FDA-regulated device product One or more of the following applies: At least one facility location is within the United States or one of its territories A device product under investigation is a product manufactured in and exported from the U.S. or one of its territories for study in another country The clinical trial has a U.S. Food and Drug Administration IDE [21 CFR part 812] Number Applicable Drug Clinical Trial Definition: A controlled clinical investigation, other than a phase 1 clinical investigation, of a drug [21 USC 321(g)(1)] product subject to section 505 [page 180] of the FD&C Act (21 U.S.C. 355) or a biological product subject to section 351 of the Public Health Service Act (PHS Act) (42 U.S.C. 262), where “clinical investigation” has the meaning given in 21 CFR 312.3 and “phase 1” has the meaning given in 21 CFR 312.21. A clinical trial of a combination product with a drug primary mode of action under 21 CFR Part 3 is also an applicable drug clinical trial, provided that it meets all other criteria of the definition under this part. [Source: 42 CFR 11.10(a); 81 FR 65139] Criteria: A clinical trial with one or more arms that meets the following conditions is an applicable drug clinical trial: Study type is interventional Study phase is other than phase 1 The clinical trial studies a U.S. FDA-regulated drug product One or more of the following applies: At least one facility location for the clinical trial is within the United States or one of its territories A drug product (including a biological product) under investigation is a product manufactured in and exported from the U.S. or one of its territories for study in another country The clinical trial has a U.S. Food and Drug Administration IND Number Exclusions The following types of studies are generally excluded from the registration and results submission requirements of FDAAA 801. This is not a complete list. Phase 1 drug trials, including studies in which investigational drugs are used as research tools to explore biological phenomena or disease processes Small clinical trials 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 Trials that do not include drugs, biologics, or devices (such as behavioral interventions) Non-interventional (observational) clinical research (such as cohort or case-control studies) Trials that were ongoing as of September 27, 2007, and reached the Completion Date (see Primary Completion Date data element on ClinicalTrials.gov) before December 26, 2007 Voluntary Submissions Note: However, a trial may be subject to the Voluntary Submissions provision of FDAAA 801. FAQs for Voluntary Submissions Voluntary Submissions Flowchart and Checklist Expanded Access Registration (and timely updates) on the availability of investigational drug products (including biological drug products) for the 3 types of Expanded Access will continue to be required to be submitted to the Clinical Trials.gov database. Reporting results to ClinicalTrials.gov is not necessary for any of the 3 types of Expanded Access. Note: Results reporting to clinicaltrials.gov is different from the Expanded Access reporting required to the FDA. [Per email communication with PRS Information Research Specialist] Elaboration of Definitions of Responsible Party and Applicable Clinical Trial. For complete statutory definitions and more information on the meaning of Applicable Clinical Trial, see Elaboration of Definitions of Responsible Party and Applicable Clinical Trial.
Submission of Registration and Results to ClinicalTrials.gov	Registration: not later than 21 days after enrollment of the first participant exception to the registration timeline for a pediatric postmarket surveillance of a device product that is not a clinical trial data elements: applicable clinical trial pediatric postmarket surveillance of a device product that is not a clinical trial expanded access for an investigational drug product studied in an applicable drug clinical trial after registration: submitting updates making corrections Results: not later than 12 months after primary completion date exceptions to the timeline for results submissions: delayed submission of results information with certification if seeking approval, licensure, or clearance of a new use delayed submission of results with certification if seeking initial approval, licensure, or clearance submitting partial results information extensions for good cause pediatric postmarket surveillance of a device product that is not a clinical trial data elements: applicable clinical trial pediatric postmarket surveillance of a device product that is not a clinical trial ***When to update your data elements: https://clinicaltrials.gov/ct2/manage-recs/faq#fr_23
Compliance	Under the statute, responsible parties, including, for example, grantee institutions, could be held accountable for noncompliance, with the potential for substantial civil monetary penalties, the withholding of grant funding from HHS agencies, and criminal proceedings. [2016 NEJM article] September 2018 FDA Draft Guidance: *Civil Money Penalties Relating to the ClinicalTrials.gov Data Bank*
Additional Resources	Summary of changes from current practice Applicable Clinical Trial [Checklist] Responsible Party Timelines Table (before 2007, after 2007, on/after final rule) FAQs 2016 NEJM article UCI HRP EQUIP Tool/Checklist for DHHS Final Rule on ClinicalTrials.gov Device Determination Stepwise Tool FDA Notices 1/16/18: Transparency: FDA to Release Portions of Redacted Clinical Study Reports J Law, Medicine, and Ethics (Winter 2017): Blueprint for Transparency at the U.S. Food and Drug Administration

National Institutes of Health (NIH) Policy on the Dissemination of NIH-Funded Clinical Trial Information

NIH Required Registration and Reporting:

The purpose of the policy is to promote broad and responsible dissemination of information from NIH-funded clinical trials through ClinicalTrials.gov. Disseminating this information supports the NIH mission to advance the translation of research results into knowledge, products, and procedures that improve human health.

What Does the NIH Policy Mean to Researchers at UCI?

The NIH Policy on Dissemination of NIH-funded Clinical Trial Information establishes the expectation that all NIH-funded awardees and investigators conducting clinical trials, funded in whole or in part by the NIH, will ensure that their NIH-funded clinical trials are registered at, and that summary results information is submitted to, ClinicalTrials.gov for public posting.

For more specific information, please review the below table and visit www.clinicaltrials.gov.

Table 2: Key Elements of the NIH Policy

Scope/Applicability	All NIH-funded clinical trials regardless of study phase, type of intervention, or whether they are subject to the regulation: 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. [decision tree (pdf)] Includes phase 1 trials of FDA-regulated drug and biological products, small feasibility studies of FDA-regulated device products, and studies of any intervention not regulated by the FDA (e.g., behavioral interventions) Applies to NIH-funded clinical trials where applications or proposals are received by NIH on or after the policy’s effective date [January 18, 2017] Applies to NIH-conducted clinical trials initiated on or after the policy’s effective date [January 18, 2017] Does not apply to a clinical trial that uses NIH-supported infrastructure which does not receive NIH funds to support its conduct The NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information covers all applications for funding (including grants, contracts, and other transactions) submitted on or after January 18, 2017 that request support for the conduct of any clinical trial. The policy does not apply to clinical trials in ongoing, non-competing awards, but will apply if the grantee submits a competing renewal application that includes a new clinical trial.† Although the policy does not apply to NIH-funded clinical trials initiated before the effective date, NIH encourage all ongoing NIH-funded clinical trials to follow it. It is also critical for investigators conducting NIH-funded applicable clinical trials that are subject to the statute and rule to be sure they are in compliance with those requirements.‡ Determining when the NIH Policy or the DHHS Final Rule applies ("Step 2") * Review your NIH Notice of Award document, in Section III (Terms and Conditions, Research and Development paragraph), to ascertain applicability. For studies initiated prior to 2017, registration and results submission is required only for studies that are an "applicable clinical trial" as defined by FDAAA; all other clinical trials are encouraged (but not required) to register and submit results. [Division of Grants Compliance and Oversight, Office of Policy for Extramural Research Administration, at NIH]
Responsibilities	Applicants seeking NIH funding will be required to submit a plan for the dissemination of NIH-funded clinical trial information that will address how the expectations of this policy will be met: if the NIH-funded clinical trial is an applicable clinical trial under the regulation and the awardee or investigator is the responsible party, the awardee or investigator will ensure that all regulatory requirements are met if the NIH-funded clinical trial is an applicable clinical trial under the regulation but the awardee or investigator is not the responsible party, the awardee or investigator will coordinate with the responsible party* to ensure that all regulatory requirements are met if the NIH-funded clinical trial is not an applicable clinical trial under the regulation, the awardee or investigator will be responsible* for carrying out the tasks and meeting the timelines described in regulation (such tasks include registering the clinical trial in ClinicalTrials.gov and submitting results information to ClinicalTrials.gov) Informed Consent documents for clinical trials within all of the above categories are to include a specific statement relating to posting of clinical trial information at ClinicalTrials.gov Each NIH-funded clinical trial should have only one entry in ClinicalTrials.gov that contains its registration and results information [expectations for clinical trial registration and summary results will be included in the terms and conditions of the NIH award] A grant award can support more than one clinical trial; the RPPR for the award may include more than one NCT#. Each clinical trial should only have one NCT# and one entry in clinicaltrials.gov [Office of Extramural Research at NIH] *Responsible Party for Registration [definition]* When the clinical trial is subject only to the NIH Policy: the recipient or investigator When the clinical trial is subject to the DHHS Final Rule: the Sponsor or the Principal Investigator, if designated by the sponsor, grantee, contractor, or awardee
Submission to ClinicalTrials.gov Timeline	Registration: Not later than 21 days after enrollment of the first participant Results: Not later than 12 months after primary completion date ***When to update your data elements: https://clinicaltrials.gov/ct2/manage-recs/faq#fr_23
Compliance	Noncompliance with the terms and conditions of the NIH award may provide a basis for enforcement actions [45 CFR 75.371, 42 CFR 11.66] [2016 NEJM article]
Additional Resources	NIH Office of Science Policy – Clinical Trials General Information Summary FAQs UCI HRP EQUIP Tool/Checklist for NIH Policy on ClinicalTrials.gov *NIH online decision tree for the definition of an NIH clinical trial* (pdf) FAQ Case Studies Training Resource: Slides, Questionnaire, Videos, Training Opportunities Annotated Form Set for FORMS-E Expectations for GCP Training NIH Policy vs DHHS Final Rule (FDAAA Section 801) NIH Notices NOT-OD-16-147 NOT-OD-17-043 NIMH NIH / FDA Protocol Template for Phase 2 and 3 IND/IDE Clinical Trials 1/4/18: Clarification regarding Case Studies 1/22/18: Clarification regarding basic health research involving fMRI 1/25/18: New Rules Governing Human Research Go Into Effect 7/20/18: NOT-OD-18-212 Delayed Enforcement and Short-Term Flexibilities for Some Requirements Affecting Prospective Basic Science Studies Involving Human Participants NIH Application Guide, Section 4.7, dissemination plan: the link to this webpage will suffice in addressing this requirement

What is the Specific Wording Required in the UCI Consent Form?

In the UCI IRB consent form in the section “WHO WILL HAVE ACCESS TO MY STUDY DATA?” include the following statement (This statement must be included verbatim):

“ClinicalTrials.gov is a Web site that provides information about clinical trials. A description of this clinical trial will be available on http://www.clinicaltrials.gov as required by U.S. Law. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time.”

Creating a profile on ClinicalTrials.gov

For research that meets any of the above definitions (see tables 1 and 2 above) that also falls outside of the School of Medicine please contact HRP Vickie Langille at 949-824-6927 to create a profile (record) on ClinicalTrials.gov.