Clinical Trials

Applying for NIH funding? Our January 16, 2018 presentation NIH Clinical Trials: 15 Minute Overview "What NIH’s Definition Means for Researchers and How the ORP Can Help" is available to view on YouTube. The presentation slides are also available as a pdf and as a Powerpoint presentation. If you need the slides in an alternative format, please contact us at ORP-QM@psu.edu.

If you are applying for NIH funding, you must know whether or not your research meets the NIH definition of a "clinical trial." If you are conducting FDA-regulated research, you must know whether or not your research meets the definition of an "applicable clinical trial" (ACT).  NIH-funded and/or FDA-regulated humans subjects research that meets a definition of either term is subject to special compliance requirements dictated by federal agencies.

The Office for Research Protections (ORP) Quality Management program is a primary resource for investigators regarding the federal regulations, policies, and definitions pertaining to clinical trials and ACTs. The program can help investigators determine whether or not their research meets a federal definition of a clinical trial or ACT, and when their research does, we support and monitor investigator compliance with federal requirements.

If you have questions related to clinical trials, please contact us at ORP-QM@psu.edu or 814-865-1775.

If you are affiliated with the College of Medicine, please contact clinicaltrials.gov@pennstatehealth.psu.edu for questions about ACTs and NIH-funded clinical trials,

Need to take GCP Training or Register on Clinicaltrials.gov?

If you are required to complete Good Clinical Practice (GCP) training, please see our see our instructions for how to access the training. If you need to register or report results in clinicaltrials.gov, you can find guidance and ORP polices on our clinicaltrials.gov information page.

Applicable Clinical Trials and FDA-regulated Studies: Medical Devices, Drugs and Biologics

"Applicable Device Clinical Trial" is a controlled study using an FDA-regulated device, excluding feasibility studies.

  • Device studies that do not require pre-market notification or appoval (i.e. are 510(k) exempt) are excluded from this definition.
  • The FDA defines feasibility studies as studies intended only to confirm the design and operating specifications of a device. Feasibility studies do not measure health outcomes.
  • The FDA's definition of "controlled" for device studies is broad. It includes studies with non-concurrent controls such as historical controls (e.g., literature, patient records), validated objective outcomes using objective performance criteria (criteria based on broad sets of data from historical databases) that are generally recognized as acceptable values, or participants as their own control. 
  • The definition does not apply to research using only de-identified human specimens.

"Applicable Drug Clinical Trial" is a controlled study using an FDA-regulated drug or biologic, excluding phase 1 studies and, in most cases, basic science. 
  • Federal regulations indicate that the types of controls generally used in clinical investigations are placebo concurrent control, dose-comparison control, no intervention concurrent control, active intervention concurrent control, and historical control. 
  • Historical control includes comparing results to literature, patient records, or the participants' baseline data, meaning the participant serves as his or her own control.

Further elaboration on these defintions can be found in the publication "The Elaboration of Defintions of Responsible Party and Applicable Clinical Trial." Contact ORP-QM@psu.edu or 814-865-1775 for help in determining whether your study is FDA-regulated and/or an applicable clinical trial.

All ACTs must be registered and have result reported on clinicaltrials.gov, a public registry and results database overseen by the National Library of Medicine. By ORP policy, ACTs must be registered within 21 days of IRB approval. By federal regulations, active registrations must be updated and verified regularly and no less than every 12 months. Results must be reported within 12 months, respectively, of final data collection for the primary outcome and final data collection for the study as a whole.

Please see our page on clinicaltrials.gov for more details on registration and reporting requirements.

Clinical Trials and NIH Policy

The NIH defines a clinical trial as "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."

The NIH definition is intentionally broad, covering a wide range of research not traditionally considered a clinical trial. A study does not need a "clinical endpoint" to meet NIH's definition of a clinical trial. The definition includes basic science, mechanistic studies, and social and behaviorial research. The NIH assumes an investigator who is applying for NIH funding has already agreed that the research outcomes are health-related. However, studies only testing the feasibility, reliability, and/or validity of a measurement or diagnostic tool may not meet the definition of "health-related biomedical or behavioral outcomes." There may be exceptions, but research that is purely observational or that is simply a review of pre-existing data, such as patient records, generally does not meet the definition of "prospectively assigned."

Though not comprehensive, the NIH provides FAQS and a number of case examples that are useful in interpreting their definition of a clinical trial.

The NIH and ORP consider the NIH definition of a clinical trial to have the same meaning as the regulatory definition a clinical trial used by other federal agencies (see "Clinical Trials and Federal Funding Other Than NIH"). However, NIH policy has more requirements for clinical trials than federal regulations, including GCP training and clinicaltrials.gov registration.

Contact ORP-QM@psu.edu or 814-865-1775 for help in determining whether your research meets the NIH definition of a clinical trial. You can also contact the NIH Program Officer identified under "Scientific/Research Contacts" in section VII of the FOA.

All applications for NIH funding require investigators to state whether or not the proposed research meets the NIH defintion of "clinical trial." Investigators do so by answering the folllowing 4 yes/no questions in the application. All answers are "yes" if the study is a clinical trial.

  1. Does the study involve human participants?
  2. Are the participants prospectively assigned to an intervention?
  3. Is the study designed to evaluate the effect of the intervention on the participants?
  4. Is the effect that will be evaluated a health-related biomedical or behavioral outcome?
 
Furthermore, NIH funding opportunity announcements (FOAs) now indicate whether or not they are specific to clinical trials. If your research meets the definition of a clinical trial, you must choose a funding opportunity that explicitly allows clinical trials, designated "Clinical Trial Optional" or "Clinical Trial Required." Applications proposing a clinical trial that are submitted to a non-clinical trial FOA will be returned without review.
 
Proposals for clinical trials also require addtional information and have additional review criteria.
 
This additional information includes a dissemination plan regarding how the investigator will fulfill clinicaltrials.gov registration and reporting requirements for NIH-funded clinical trials. The plan must contain sufficient information to assure the following:

  • the applicant will ensure that clinical trial(s) under the award are registered and results information is submitted to ClinicalTrials.gov as outlined in the policy and according to the specific timelines stated in the policy;
  • informed consent documents for the clinical trial(s) will include a specific statement relating to posting of clinical trial information at ClinicalTrials.gov; and
  • the recipient institution has an internal policy in place to ensure that clinical trials registration and results reporting occur in compliance with policy requirements.
 
The following Penn State-specific language may be helpful in outlining a dissemination plan:
 

The PI will serve as the responsible party for the clinicaltrials.gov record(s) associated with the study or studies funded by the award. He/she will ensure the trial is registered no later than 21 days after IRB approval, following policy at the Pennsylvania State University. Once a record is established, the PI will confirm the accuracy of record content, resolve problems, and verify and update the record. The PI will also report results and adverse events in clinicaltrials.gov within 12 months of the primary and study completion dates respectively. The Pennsylvania State University Office for Research Protections Quality Management program monitors and enforces investigator compliance with required registration and reporting in clinicaltrials.gov. As the PRS administrators for the University, the Quality Management program assists investigators serving as the responsible party in the registration, record maintenance, and reporting processes, including providing deadline reminders and guidance for resolving errors. As part of the review process, the IRB will confirm that the consent form(s) fulfill NIH policy by requiring a specific statement relating to the posting of the study or studies on clinicaltrials.gov.

GCP Training: All study team members on an NIH-funded clinical trial must complete Good Clinical Practice (GCP) training before a study can receive IRB approval, and the training must be refreshed every 3 years. This is in addition to the human subjects training required by the IRB, which also must be refreshed every 3 years.
 
Penn State offers GCP training through the CITI Program. Please see our our instructions for how to access the training.
 

Clinicaltrials.gov Registration and Reporting: All NIH-funded clinical trials must be registered and have results reported on clinicaltrials.gov, a public registry and results databased overseen by the National Library of Medicine. By ORP policy, clinical trials must be registered within 21 days of IRB approval. By NIH policy, active registrations must be updated and verified regularly and no less than every 12 months. Results must be reported within 12 months, respectively, of final data collection for the primary outcome and of final data collection for the study as a whole.

Please see our page on clinicaltrials.gov for more details on registration and reporting requirements.

Clinical Trials and Federal Funding Other Than NIH

A number of federal funding agencies share a definition of "clinical trial" that is codified in federal regulations which will be effective January 21, 2019. These regulations define a clinical trial as "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 the interventions on biomedical or behavioral health-related outcomes."

You can find all the federal funding agencies that adopt this definition at the following link: www.hhs.gov/ohrp/regulations-and-policy/regulations/common-rule/index.html.

The regulatory definition is intentionally broad, covering a wide range of research not traditionally considered a clinical trial. A study does not need a "clinical endpoint" to meet this regulatory definition of a clinical trial. The definition includes basic science, mechanistic studies, and social and behaviorial research. There may be exceptions, but research that is purely observational or that is simply an analysis of pre-existing data generally does not meet the definition of "prospectively assigned."

The NIH and the ORP take this definition to have the same meaning as the definition of "clinical trial" used by the NIH.

If you have questions about whether your study meets this definition, you can contact Quality Management at ORP-QM@psu.edu or 814-865-1775. However, your IRB Analyst will help you with this definition when you submit a new study for IRB approval.

Federal regulations require that an investigator receiving federal funding for a clinical trial, except clinical trials sponored by the NIH or FDA, post a consent form approved by the IRB any time after recruitment closes but not later than 60 days after the last study visit by any subject. The consent form must be posted on a publicly available federal repository.  

The federal agencies have not yet identified the federal respository or repositories but are considering whether to use clinicaltrials.gov for this purpose.