NIH Clinical Trial Overview and Registration

NIH Clinical Trial

NIH Clinical Trial Overview and Registration

 

 

News

Continued Extension of Certain Flexibilities for Prospective Basic Experimental Studies with Human Participants

May 6, 2024

"The purpose of this notice is to further extend interim policy flexibilities, regarding registration and results reporting for a subset of NIH-funded research whose primary purpose is basic experimental studies with humans (BESH) submitted in response to designated BESH Notices of Funding Opportunity (NOFOs)... NIH is extending the period of delayed enforcement for registration and results reporting, originally announced in NOT-OD-18-212, for BESH responsive to designated BESH NOFOs with application due dates through September 24, 2025."

 

HHS Updates Regulations to Reflect Required Annual Inflation-Related Increases

November 5, 2019

The Department of Health and Human Services has updated its regulations to reflect required annual inflation-related increases to the civil monetary penalties in its regulations. So, what does that mean? Essentially, as of November 5, 2019, FDA can now fine the responsible party $12,103 for a single adjudication, and then $12,103 per day after 30 days that the problem is not corrected for failing to submit required registration or results information to ClinicalTrials.gov for an Applicable Clinical Trial (ACT).

 

NIH Extension of Certain Flexibilities for Prospective Basic Experimental Studies with Human Participants 

July 24, 2019 

"This extension will last through September 24, 2021. During this extension period, NIH will continue implementation of initiatives launched in 2016 aimed at assuring that NIH and NIH-funded scientists maximize stewardship and transparency. However, delayed enforcement for BESH registration and results reporting will allow NIH to engage in further conversations with the BESH community to gain a deeper understanding of the scientific and technical needs to best facilitate (in a least burdensome way) registration and reporting of BESH studies while ensuring this information is scientifically useful."  

In 2016, NIH launched a multi-faceted effort to enhance its stewardship over clinical trials. The goal of this effort is to encourage advances in the design conduct, and oversight of clinical trials while evaluating the entire research enterprise to a new level of transparency and accountability.

(On March 23, 2021, this notice was replaced by NOT-OD-21-88 further extending these flexibilities until September 24, 2023.)

 

NIH Clinical Trial Overview

 

This overview is primarily focused on funded NIH clinical trials. University of Colorado Colorado Springs (UCCS) faculty, staff, and students conduct a diverse array of human subjects research projects, including NIH-funded projects that qualify as clinical trials. With this in mind, the Office of Sponsored Programs and Research Integrity (OSPRI) and the Institutional Review Board (IRB) at UCCS requires that all funded research that qualifies as a clinical trial meet the training and reporting requirements set forth by the NIH for NIH-funded clinical trials. The requirements can be found in in the “NIH Policy on Dissemination of NIH-Funded Clinical Trial Information ” and the “Policy on Good Clinical Practice Training for NIH Awardees Involved in NIH-funded Clinical Trials .” 

Additional information regarding training and reporting requirements can be found in the IRB Special Topics XXXII: IRB Policy for NIH Funded Clinical Trial Compliance. 

 

 

NIH might consider your human subjects research to be a clinical trail. Does your study…

  • Involve one or more human subjects?
  • Prospectively assign human subject(s) to intervention(s)?
  • Evaluate the effect of intervention(s) on the human subject(s)?
  • Have a health-related biomedical or behavioral outcome?

If you answer “yes” to all of the questions above, your NIH-funded study is considered a clinical trial. Unsure how to answer the questions? This NIH Clinical trail tool can help.

Helpful Definitions

Defining
Key Terms for Clinical Trials
  • Clinical Trial
    Clinical Trial

    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. (adapted from the Notice of Revised NIH Definition of “Clinical Trial ”)

  • Intervention
    Invervention

    With regards to NIH-funded clinical trials, an intervention is defined as a manipulation of the subject or subject’s environment for the purpose of modifying one or more health-related biomedical or behavioral processes and/or endpoints. (adapted from the Notice of Revised NIH Definition of “Clinical Trial ”)

    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.

    Depending on the study, a non-UCCS (outside) IRB review may be required. Please contact the IRB as soon as possible to explore the use of a non-UCCS IRB.

  • Health-Related Biomedical or Behavioral Outcome
    Health-Related Biomedical or Behavioral Outcome

    With regards to NIH-funded clinical trials, this 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. (adapted from the Notice of Revised NIH Definition of “Clinical Trial ”)

    Examples include:

    • positive or negative changes in physiological or biological parameters (e.g., improvement of lung capacity, gene expression);
    • 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 life.

Clinical Trials Registration

 

All NIH-funded clinical trials are expected to register and submit results information to ClinicalTrials.gov , as directed by the "NIH Policy on Dissemination of NIH-Funded Clinical Trial Information " for competing applications and contract proposals submitted on or after 1/18/2017.

Some studies not funded by NIH may also require submission per the Applicable Clinical Trials (ACTs). These primarily involved studies falling under FDA regulation. The ACT Checklist and ClinicalTrials.gov FAQ can help to identify these studies. Please also review the FAQ item "Do I need to register my clinical trial?" in the section below. 

ClinicalTrials.gov is a public website designed by NIH and hosted by the National Library of Medicine. For reporting and compliance purposes with ClinicalTrials.gov, the Principal Investigator will be designated as the Responsible Party.

ClinicalTrials.gov registration and reporting requirements include the following:

  • Registration – The study must be registered on ClinicalTrials.gov within 21 days after the first subject is enrolled. Registration information includes descriptive information, recruitment information, location and contact information, and administrative data.
  • Updates – The information in the clinical trial records must be updated at least once every 12 months.
  • Results – The study results must be reported on ClinicalTrials.gov within 1 year of the final collection of data. Results information includes participant flow, demographic and baseline characteristics, outcomes and statistical analyses, adverse events, the protocol and statistical analysis plan, and administrative information.

Contact the campus PRS administrator via IRB@uccs.edu to request an account.

The Principal Investigator requesting the account is the Responsible Party (RP) and is responsible for conducting the study, has access and control over the data, and has the right to publish the results and data entry into ClinicalTrails.gov. Ongoing responsibilities include:

  • Updating the record every 12 months and within 30 days of changes or amendments that affect the information in the record, e.g., recruitment status, total enrollment, primary completion date, and contact information
  • Reviewing the record at least once every 12 months, even if there are no changes
  • Responding to any questions from the campus PRS administrator or ClinicalTrails.gov

The NTC number (or ClinicalTrials.gov identifier) you receive upon registration will need to be reported to the IRB once received. The NTC number is a unique identification code given to each clinical study when it is registered on ClinicalTrials.gov. Please submit the UCCS IRB protocol number and the NTC number to the IRB via email at irb@uccs.edu.

 

ResearchMatch.org

researchmatch.org logo

UCCS has partnered with ResearchMatch, a NIH-sponsored recruitment service for research with health outcomes. Visit our ResearchMatch Information page if you are interested in signing up.

 

GCP Training

 

The principles of Good Clinical Practice (GCP) help assure the safety, integrity, and quality of clinical trials by addressing elements related to the design, conduct, and reporting of clinical trials. NIH expects all NIH-funded clinical investigators and clinical trial staff who are involved in the design, conduct, oversight, or management of clinical trials to be trained in GCP. Additional information regarding the training are available at the Good Clinical Practice Training website.

 

Resources

 

 

Questions? Contact the OSPRI Compliance at composp@uccs.edu

 

FAQ

Clinical Trials FAQ

 

How do federal regulations define clinical trials?

A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may or may not include placebo or other control) to evaluate the effects of the interventions on biomedical, behavioral health-related, and some educational interventions outcomes. (45 CFR 46.102(b)) . A study with a single intervention can qualify as a clinical trial.

Some studies (e.g., some basic experimental studies involving humans (BESH) might not fit intuitively in this definition, even though they may be clinical trials. In these cases, it can help to pay close attention to sponsor communications to determine whether the sponsor considers the study to be a clinical trial.

What reporting requirements do I have if my research meets the definition of an NIH funded clinical trial?

If your research meets the definition of a clinical trial, your reporting requirements are two-fold:

  • Per 45 CFR 46.116(h) , for each clinical trial conducted or supported by a Federal department or agency, one IRB-approved informed consent form used to enroll subjects must be posted by the awardee or the Federal department or agency component conducting the trail on a publicly available Federal web site to be specified by the sponsoring agency.  The posting can take place at any time after recruitment closes, but no later than 60 days after the last study visit by any subject.
  • If the research is sponsored by NIH, registration and reporting of the clinical trial at ClinicalTrials.gov is required.  Additional information is available on this website. Additional information is available in Special Topics: XXXII IRB Policy for NIH Funded Clinical Trial Compliance of the University of Colorado Colorado Springs SOPs.

In most cases, the sponsor will inform you of your reporting requirements, so be sure to read sponsor communications carefully.

What is UCCS's process for clinical trials?
  1. Determine whether your clinical trial requires registration using the resources on this page and in these FAQs. Contact the IRB at irb@uccs.edu if you believe you need to register or if you are unsure.
  2. Email irb@uccs.edu with a request to set-up an account once you have decided you need to report your clinical trail (UCCS has an organizational PRS account)
    • It may take a few days for your account to be created. You should receive an email with log-in instructions once your account is created.
  3. Follow the directions outlined in Section 4-5 of the PRS User Guide for creating a record for your clinical trial.
  4. Submit your NCT (which you will receive after your trial is registered) and IRB protocol number to irb@uccs.edu. This clinical trial identifier number will be recorded on your protocol’s IRBManager page.
  5. Throughout your study, ensure that you are following the terms and expectations of ClinicalTrials.gov. You will be responsible for making sure the terms are followed and your trial is kept up to date. Please also notify the IRB if any deviations or changes occur. You will need to report these changes and/or deviations to the IRB through normal IRB forms. Please contact the IRB with questions.
Do I need to register my clinical trial?

You will need to register your clinical trial if it is sponsored by the National Institute of Health. You may also need to register your trial if it is considered an Applicable Clinical Trial (ACT). These trials have specific characteristics, such as involving FDA regulated drugs or devices, and require registration with ClinicalTrials.gov. The NIH has published a checklist for evaluating whether a clinical trial or study is an ACT and flowchart for identifying an ACT to help make this determination. In general, your study must be registered within 21 days of enrolling your first participant. Please contact the IRB with any questions about whether you are required to register.

How do I register my clinical trial?

To register your trial, you will to contact the campus PRS administrator via IRB@uccs.edu to request an account to be set up in ClinicalTrials.gov’s Protocol Registration and Results System (PRS). UCCS has an organizational PRS account that is manged by the IRB. After applying for an account, you may receive a email from ClinicalTrails.gov that will require you to complete the process. It may take a few days for your account to be created. After you have obtained your account, follow the directions in Section 4-5 of the PRS User Guide to enter your clinical trial information into the registration system. Be sure to also review your responsibilities and expectations as a user of the PRS and Responsible Party of your study. For example, familiarize yourself the deadlines associated with updates . Once your trial is registered, you will receive an identifier (NCT number). Please send that number, along with your IRB protocol number, to irb@uccs.edu.

Does UCCS have an organizational PRS account?

At this time, UCCS has an organizational or institutional Protocol Registration and Results System (PRS) account. Contact the campus PRS administrator via IRB@uccs.edu to request an account.

Can I register my unfunded clinical trial?

You are not required by regulations to register a clinical trial unless it qualifies as an Applicable Clinical Trial (ACT) or is funded by the NIH. Please review the resources on this page to determine whether you are required to register. If you are not required to register your trial, you can still elect to do so at ClinicalTrials.gov.

Please carefully read the Responsible Party’s responsibilities to ensure that all rules and requirements are met. Please be aware that your consent form must inform participants that your results will be registered online; this is a requirement for consent forms for NIH-funded studies but must also be present for unfunded studies. Example language can be found on the “Example Informed Consent Language” on the IRB’s main webpage. Lack of this disclosure will likely affect whether you are able to register your trial, especially if it has already ended and you are registering retroactively.

Can I report my unfunded clinical trial results after the trial is over?

You may elect to register your unfunded clinical trial results after the trial is over. The consent form for the study must have informed participants that the results will be registered online. This may affect whether you’re able to register your unfunded clinical trial results. Example language can be found on the “Example Informed Consent Language” on the IRB’s main webpage.

To register, you will follow the same steps as registering your sponsored trial, listed in the above FAQ item “What is UCCS’s process for clinical trials?” You may also wish to review ClinicalTrials.gov’s guide on reporting results. Please be aware that registering your trial results may require you to follow terms of use for ClinicalTrials.gov which may be ongoing. Ensure you are aware of your responsibilities before electing to report unfunded clinical trial results.

Where can I learn more about clinical trials?

Along with the information on this page, you may also want to read more about clinical trials at ClinicalTrials.gov.

What happens if I don't register a clinical trail?

Not registering a required clinical trail may impact:

  • Institution and Investigator Reputation
    • Public notice of noncompliance and violations
    • Withholding of remaining or future grant funds
    • Other regulatory sanctions
  • Civil monetary penalties up to $12,462 per day, per study
  • Some journals may require registration to publish (see the International Committee of Medical Journal Editors guidelines)