Procedure 4: Review and Approval for Clinical Trials

Effective Date: 04 April 2026

Responsible Office: Office of the Vice Provost for Research

Last Updated: 03 August 2026

I. Scope & Purpose

This procedure applies to all faculty, staff, students, and affiliated researchers at William & Mary (W&M) who conduct human subjects research overseen by the W&M Institutional Review Board (IRB) within the scope of their roles.

The purpose of this procedure is to outline W&M’s process for addressing research involving human subjects that also meets the criteria for a clinical trial. Clinical trials must comply with requirements that do not apply to other types of human subjects research. These requirements are designed to address the increased participant vulnerability and risks associated with many clinical trials compared with other research.

II. Definitions

1. Clinical Trial
   1. A clinical trial is a type of human subject research study.
   2. Clinical trials try to answer a research question about health-related outcomes by prospectively assigning human participants to either a control group or one or more interventions to evaluate the effects of the intervention on biomedical or behavioral health-related outcomes.
   3. An intervention is the act of interfering with an outcome, course of action, treatment, condition, health-related curriculum, or process in some way.
   4. Clinical trials are the primary way that researchers find out if a new treatment, course of action, condition, process, or curriculum (like a new drug, diet, therapy, movement, health curriculum, or medical device) is safe and effective.
   5. A health-related outcome is an outcome from the intervention being studied that directly influences a human as related to their physical health, psychological health, or behavior.
2. Behavioral health-related outcome: This is a change in a person's behavior that directly affects their health and wellness. This is often measured by behavioral assessments, psychological assessments, self-reporting, or observation. This can be a curriculum, a psychological method, a behavioral intervention, the use of a wearable, etc.
3. Biomedical health outcome: This is an outcome directly related to the physical body. This can be measured through physical examination, lab testing, images, self-report, or observation. A biomedical outcome is directly related to the physical body and the changes the physical body undergoes because of the intervention being studied
4. A transient health-related outcome is sufficient for a study to be considered a clinical trial if all other elements of the clinical trial definition are met.

III. Procedure

The clinical trials requirements in 45 CFR 46.116(h) apply to all non-exempt research that is federally funded, subject to the FDA, DoD, or USDA regulations for human subject research, can be considered cooperative research, and research that is contractually obligated to follow the federal regulations governing human subjects research. The clinical trials requirements do not apply to other human subjects research completed by William & Mary researchers.

 A. Determining if a Study is a Clinical Trial

 The following criteria are used to determine whether a study is a clinical trial. Risk is not considered when determining if a study is a clinical trial. All of the statements must be true for the study to be categorized as a clinical trial by William & Mary.

1. The study is subject to federal oversight, either because:
   1. the study is federally funded by a signatory of the Common Rule;
   2. the research is affiliated with a contract with a sponsor or another group that requires you to adhere to 45.CFR.46;
   3. the study is subject to Food and Drug Administration (FDA) regulations;
   4. the study is subject to the Department of Defense (DoD) regulations
2. The study meets the regulatory definition of research
   1. The study is a systematic investigation and designed to develop or contribute to generalizable knowledge; OR
   2. The study uses drug(s), biological product(s), medical device(s), or nutritional products (e.g., dietary supplements or foods) that are under the oversight of the Food and Drug Administration (FDA)
3. The study meets the regulatory definition for “human subject”
   1. The study involves live humans;
   2. The study generates information about live humans
4. The participants are prospectively assigned to an intervention group
   1. There might be a control group that does not get the intervention the principal investigator is researching. There is always an intervention group that is exposed to the intervention(s) being researched
   2. Some researchers add more groups beyond the two (control and intervention) groups to see if variations in the interventional protocol might work, but this is not a requirement of qualifying as a clinical trial.
5. The study is designed to evaluate the effect of the intervention on the participants
   1. The principal investigator is specifically evaluating an intervention.
      1. Interventions are different from measurements. Measurements are used to collect data, while interventions are used to modify health-related endpoints.
      2. A manipulation or modification in an individual’s behavior or environment for the purpose of measurement alone is not considered a clinical trial.
   2. A manipulation or task is an intervention if it is used to modify a health-related biomedical or behavioral outcome.
      1. However, a manipulation or task used expressly for measurement, and not modification, would not be an intervention.
   3. Observational studies which do not include an intervention are not considered clinical trials.

B. Researcher Requirements

1. All investigators need to complete the required human subjects research training outlined by the William & Mary IRB. Additional training may be required by the sponsor or any federal agency providing oversight for the study.
2. It is the responsibility of the principal investigator to verify that all human subjects research training requirements have been met before the implementation of a clinical trial.

C. Use of Single IRB

1. If the research team is made up of researchers from William & Mary and other organizations/institutions, the study must be reviewed by one IRB, called the IRB of Record.
2. The IRB of Record is typically the IRB affiliated with the site where most of the work with human participants is being conducted. Any collaborators from other institutions must be named on the reviewed and approved IRB application. Additionally, a reliance agreement or individual investigator agreement must be filed in accordance with William & Mary’s standard for Cooperative Research.

D. IRB Submission Requirements

1.  The IRB application must discuss the health-related outcomes that the study is examining.
2. The IRB application must discuss the best practices and “standard of care” as related to the study’s intervention(s).
3. The consent/parental permission/minor assent must include information about the study as a clinical trial.

E. Study Registration and Reporting Requirements

Once IRB approval is received, the researcher must register the study on ClinicalTrials.gov prior to the enrollment of the first participant but no later than 60 days after the last study visit with the last participant. This includes:

1. Registering the study on clinicaltrials.gov by completing their application and responding to all administrative feedback from the PRS administrators
2. Posting information about the study on the clinicaltrials.gov website
3. Updating study information, no less than every 12 months
4. Report aggregated results to clinicaltrials.gov within 12 months of data collection completion.
5. If a sponsor (e.g. NIH) or any other applicable authority imposes (e.g. ICMJE) imposes a different expectation, the most conservative requirement will apply.
6. For example, NIH clinical trials are required to be registered in ClinicalTrials.gov no later than 21 calendar days after the enrollment of the first participant.

 F. Compensation for Clinical Trials

The issue of compensation raises concerns for vulnerable populations including minors, people who lack the capacity for decision-making, and people with financial difficulties. The William & Mary IRB expects all researchers to avoid undue influence and coercion and to design a compensation plan.

G. IRB Office Review and Processing

1.  The William & Mary IRB office will assess the study to ensure that all criteria are met for a clinical trial determination.
2. The IRB application and reviewer comments reflect the applicability of this policy with the information as to why the study is considered a clinical trial
3. IRB office staff will register the principal investigator’s William & Mary email with clinicaltrials.gov so the investigator can register their study with clinicaltrials.gov once IRB approval is received.
4. The IRB office does not manage any clinicaltrials.gov processes or data entry
5. When the study is approved, the IRB office staff will generate a clinical trial approval letter with information about the researcher's responsibilities regarding the clinical trial. This includes registration/login information to clinicaltrials.gov.

 IV. Authority & Amendment

 This procedure was approved by the William & Mary IRB on April 4, 2026. This procedure will be reviewed every 2 years to ensure it remains relevant, usable, and in compliance with university policy and relevant law.

 V. Related Policy & Procedures

• Federal Regulations Governing Research with Human Subjects 45.CFR.46
• The Belmont Report
• Nuremberg Code of 1947
• Office for Human Research Protections (OHRP)
• Code of Virginia, Research with Human Subjects
• William & Mary Policy for Conflicts of Interest
• William & Mary Policy for Financial Conflicts of Interest
• William & Mary Research Compliance Website
• William & Mary Data Classification and Protection Policy
• FDA Regulations
  • 21.CFR.50 Protection of Human Subjects
  • 21.CFR.56 Institutional Review Boards
  • 21.CFR.312 Investigational New Drug Application
  • 21.CFR.812 Investigational Device Exemptions
  • 21.CFR.600 Biologics
• DoD Regulations Governing Research with Human Subjects 32.CFR.219
• DoD Instructions 3216.02
• NIH Website for Human Subjects’ Research
• NSF Website for Human Subjects’ Research
• William & Mary’s Policy for Research with Human Subjects
• William & Mary’s Policy for Research Misconduct

Appendix A: ClinicalTrials.gov Registration and Posting of Research Results

Registering Your Study

1. Once you have received formal email notification that your IRB protocol was approved by the William & Mary IRB, you must register your study on clinicaltrials.gov website’s PRS portal. Please see the approval letter uploaded with your IRB application for information about clinicaltrials.gov.
2. If your clinical trial is subject to the FDA regulations, you have 21 days to complete this. If your study is not subject to the FDA regulations, the informed consent form must be posted after the clinical trial is closed to recruitment, and no later than 60 days after the last study visit by any participant, as required by the protocol
3. You must have a PRS account to register a study. This should be issued with approval from the William & Mary IRB. The William & Mary IRB, as a PRS-affiliated organization, will initiate an account application for you (creating your login access). If you did not receive information about your PRS account, please email the William & Mary IRB to request a PRS log-in. 
4. Once you have logged into the PRS portal, you will click on the “Records” button on the left-hand, upper third of your screen. A menu of options will appear and you want to select “New Record.”  You will need to complete all sections of the application, upload the requested documents, and submit the application to PRS. It’s okay to copy and paste whatever you need from your IRB application into the PRS portal, but the questions sometimes are very different from what the William & Mary IRB asks. Furthermore, PRS’ word allotment is far smaller than the word limit of the IRB application’s narrative response sections.
5. Registration must include the following information:
   • Description (title, design, primary outcome measure information)
   • Recruitment information (eligibility criteria, recruitment study, why study stopped if applicable)
   • Location and contact information (name of sponsor, facility/PI/research team contact information)
   • Administrative data (secondary ID, IRB protocol status)
6. The PRS Administrators will review your application for completeness. When the application passes review by the PRS Administrators, your study will be posted to the ClinicalTrials.gov website.
7. Your application will be processed by the National Library of Medicine at the National Institutes of Health (NIH), typically within 48 business hours. They will also manage your ongoing access and interface within the PRS system. Because the William & Mary IRB does not administer the PRS system, you will need to direct most questions about the PRS system to the PRS Administrators.

Posting Your Results

• After your data collection is complete, you have 12 months to post your aggregated data to the PRS portal. You’ll use the same login that you did to register the study. If you lost or cannot remember your PRS log-in, please email the PRS Administrators. Unfortunately, the William & Mary IRB has no administrative privileges to reset your PRS log-in.
• As of 2019, the following information is requested by the PRS portal for reporting research results: participant flow, baselines, and outcomes within the scope of the research; what, if any, adverse events occurred, limits and caveats of the research results, and who to contact for more information about the study. Complete all research results application sections and submit for review by the PRS Administrators. Once approved, the research study results will be posted to the clinicaltrials.gov website.
• Be prepared to include in your PRS research results application:
  • Progress of participants in each treatment group, including the number who started and completed the trial
  • Participant demographics and baseline characteristics (age, sex, gender, race, ethnicity, and all other measures assessed at baseline) that are used in the analyses of the primary outcome measures
  • Outcomes and statistical analyses for each primary and secondary outcome measured by treatment group or comparison group, including results of scientifically appropriate statistical analyses performed on these outcomes, if any
  • Table of all anticipated and unanticipated serious adverse events and other adverse events that exceed a 5% frequency threshold within any group, including the time the event occurred, a description of the event, collection approach (systematic or non-systematic), and a table with the number and frequency of deaths due to any cause of treatment group or the comparison group
  • Administrative information, including a point of contact to obtain more information about the posted summary results information

Appendix B

Examples of Clinical Trials

•  Educational Research
  • You are a teacher and you want to study if sleep deprivation is affecting student performance. You design an intervention where students learn different behaviors to improve sleep. You then measure their performance on a standardized test. This is a clinical trial because you are assessing an intervention on a behavioral health-related outcome.
• Social-Behavioral Research
  • You are a therapist, and you want to research if the treatment plan you have created to help people newly diagnosed with a disease is effective in their coping with the diagnosis. This is a clinical trial because it is assessing the intervention that addresses a mental health-related outcome.
  • You are a researcher who has developed an intervention for smoking cessation that includes a meditation lesson hosted in virtual reality. These meditation practices are designed to encourage participants to stop smoking. You later survey the participants to measure if they quit smoking. This is a clinical trial because you are assessing an intervention on a behavioral health-related outcome.
• Biomedical Research
  • You are researching if certain foods do or do not affect blood glucose and if intervening on the diet of a person will affect their blood glucose. This is a clinical trial because it is assessing the intervention with a physical health outcome.
  • You are a researcher who would like to study the effect of maximum effort weightlifting on muscle tension. You design an intervention where participants lift increasingly heavy weights until they are no longer able to complete the task and then measure their muscle tension using electromyography. This is a clinical trial because it is assessing the intervention with a physical health outcome.
  • You are a researcher who has developed an application for a smartphone that provides meal plans for diabetics based on their blood sugar levels. You use a survey to measure their blood sugar levels before and after the intervention. This is a clinical trial because it is assessing the intervention with a physical health outcome.
  • You are a coach and you want to study the efficacy of a dietary supplement on baseball players' performance. The study includes a randomized trial where the athletes are given the supplement or a placebo and are asked to complete standard physical tests before and after the intervention. This is a clinical trial because it is assessing the intervention with a physical health outcome.
  • You are a researcher who has developed a new filter for a respiration device used by firefighters. You test the filter by exposing firefighters to pollutants in a lab setting while they complete exercises. You measure their lung capacity before and after the intervention. This is a clinical trial because it is assessing the intervention with a physical health outcome.
  • You are a biomedical engineer and you have developed a prosthetic limb. You want to test the safety and efficacy of the prosthetic. You design a study where participants complete tasks while wearing the limb while you take measurements and survey the participants for fit and comfort levels. This is a clinical trial because it is assessing the intervention with a physical health outcome.
  • You are a doctor and you would like to study the effect of a drug that has been approved to treat liver disease on patients with cystic fibrosis. You design a study to measure the effects on the level of a biomarker associated with the severity of cystic fibrosis. This is a clinical trial because it is assessing an intervention on a health-related biomedical outcome.

Studies that are not Clinical Trials

• You are a researcher who has partnered with a school. The school is implementing a health intervention with minors as a part of its curriculum. All students will participate in the health intervention and pre/post assessments. This is not a clinical trial because the intervention is not implemented by the researcher and is considered a normal part of the curriculum and even if the researcher helps with implementation and data from the normal educational practice is shared with the researcher, this does not change the determination. 
• You are a researcher studying participant attitudes toward CT scans for cancer patients. You distribute a survey before and after CT scans that are standard of care and not part of the research study. This is not a clinical trial because it does not include an intervention.
• You are a researcher studying genetic mutations. You take a blood sample from participants and perform genomic analysis. This is not a clinical trial because sample collection is not an intervention in this context.
• You are analyzing identifiable medical records of patients who were treated with an approved drug for prostate cancer. The study is designed to evaluate a protein in the blood for patients who received therapy with the drug. This is not a clinical trial because it does not include an intervention.
• Physicians report that a drug used for treating cataracts also has positive results for patients who also have an eating disorder. The researcher developed a survey to ask participants if the drug has affected their eating disorder. This is not a clinical trial because there is no intervention and the survey is used as a measurement and not to modify a behavioral or biomedical outcome.