IRB Procedures

Procedure 1: Addressing Noncompliance in Human Subjects’ Research

Under development

Procedure 2: Human Subjects Research Eligible for Exemption

I. Scope & Purpose

This procedure applies to all faculty, staff, students, and affiliated researchers working within the scope of their roles at William & Mary (W&M) who conduct human subject research as defined by federal regulations (45 CFR 46) and overseen by the W&M Institutional Review Board (IRB). The purpose of this procedure is to outline W&M IRB’s standard operating practices for conducting administrative review that results in an exemption determination.

Effective Date: 04 April 2026
Responsible Office: Office of the Vice Provost for Research
Last Updated: 03 August 2026

II. Definitions

1. Benign Behavioral Interventions: Benign behavioral interventions are brief, harmless, painless, not physically invasive, not likely to have a significant adverse lasting impact on the participants, and the investigator has no reason to think the participants will find the interventions offensive or embarrassing. Benign behavioral interventions can never be a clinical trial.
2. Deception: Deception refers to providing false information to prospective participants.
3. Exemption: Exemption from the federal regulations governing human subjects research at 45 CFR 46 includes activities in which the only involvement of human participants will be in one or more of the categories detailed in 45 CFR 46.104(d) and Appendix A of this procedure. Research studies that fall into the eligible categories are not required to adhere to the federal regulations governing research with human participants but are required to adhere to any other applicable laws, contractual obligations, and W&M University policies, procedures, and standards.
4. Exemption Determination: A determination made by the W&M IRB regarding a submitted human subjects research protocol.
5. FLEX Exemption: When a study is solely subject to the W&M policy for human subjects’ research and not subject to the federal regulations at 45 CFR 46 governing research with human participants, some research protocols may be reviewed and approved under the W&M special exemption category - “FLEX Exemption,” This review process and determination is designed to provide ethical protections equivalent to those found in 45 CFR 46, while also reducing administrative workload and regulatory excess. Refer to section B of this SOP for details.
6. Funded or Sponsored Research: A sponsored or funded research project has a defined scope of work and a set of objectives supported by external funds.
7. Incomplete Disclosure: Incomplete disclosure is when information about the real purpose or nature of the research is withheld from participants.
8. Limited Review: A limited review pertains to research in which the primary risks to participants relate to privacy and confidentiality. Research that qualifies for an exemption requiring limited IRB review would have required IRB review and approval either through the expedited review procedure or by a convened IRB review under the pre-2018 Requirements. A limited review is performed by an IRB board member where, as opposed to considering all the criteria for IRB approval, the reviewer must review specific, more limited aspects of a proposed research study related to participant privacy and confidentiality. A determination that there are adequate provisions to protect the privacy of participants and to maintain the confidentiality of data must be found.
9. Minimal Risk: Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.
10. Not Human Subjects Research: Research activities are considered “Not Human Subjects Research (NHSR)” when they do not meet the definition of “research” or “human subjects” as defined by 45 CFR 46, and the W&M University Policy for completing research with human participants.
11. Readily Ascertainable: Readily ascertainable is when the identity of the individual participant can be obtained, discovered, or determined without significant difficulty or effort. Identities of participants are considered “readily ascertainable” when the data are:
    • directly identifiable,
    • linked to a master list that the researcher(s) can access,
    • indirectly identifiable to any member of the research team due to their access, role, or expertise, or
    • identifiable from the content of the data, triangulation of data points, pairing with other data, or sample size.

III. Procedure

All W&M University researchers conducting human subjects research must submit an IRB protocol to the IRB for review and approval before implementation, including study protocols eligible for exemption.

When an IRB protocol is required to be reviewed under 45 CFR 46, the IRB Chair (or their designee(s)) will conduct reviews resulting in an exemption determination for minimal risk research eligible for exemption under 45 CFR 46 and the W&M University Policy, including this standard.

 When not obligated to apply 45 CFR 46 to an IRB protocol, the IRB Chair (or their designee(s) will conduct reviews resulting in an exemption determination for minimal risk research in accordance with only the W&M University Policy, including this standard.

1. All Exemption Categories under 45 CFR 46 as noted in Appendix A and limitations detailed in Section E of this procedure, are applicable when research with human participants is considered:
   1. Subject to the DoD, USDA, FDA regulations, or any other signatories of the Common Rule, or
   2. Sponsored or Funded from any external source, or
   3. Contractually Obligated, or
   4. Associated with an Agreement, or
   5. Cooperative
2. All Exemption Categories under 45 CFR 46, as noted in Appendix A and limitations detailed in Section E of this procedure, are applicable when research with human participants may become funded. This includes a plan for future federal sponsorship (e.g., proof of concept studies for federal RFPs, pilot studies intended to support a federal grant application, training and program project grants, no-cost extensions).

1. All Exemption Categories under 45 CFR 46 as noted in Appendix A of this procedure, are applicable to this section. 
2. W&M FLEX Exemption Category: 
   1. W&M’s FLEX special exemption category is designed to provide protections equivalent to those found in 45 CFR 46, while also reducing administrative workload and regulatory excess.
3. Research Protocol Eligibility for W&M FLEX Exemption: Research that is eligible for FLEX exemption are those that are not listed in Section II.A of this policy and are no more than minimal risk to participants. Participants can be adults and/or minors, and the research can include one or more of the following research procedures:
   1. benign behavioral interventions;
   2. observations of behavior, surveys, interviews, or focus groups;
   3. non-invasive collection of human body data such as weight measurement using a scale, height measurement using a tape measure, or tracking eye movement with an eye tracker; or
   4. use of secondary private identifiable or indirectly identifiable data for research.
4. Post-Approval Obligations for FLEX Special Exemption Category Studies
   1. After a study is approved by the W&M IRB office under the FLEX special exemption category, the Principal Investigator is responsible for submitting project revisions to the W&M IRB office in advance of initiating any changes
   2. If the proposed revisions render the study ineligible for the FLEX special exemption category, the PI must revise the protocol to bring it into compliance with 45 CFR 46. It is the responsibility of the PI to notify the W&M IRB office of any changes related to eligibility for the FLEX special exemption category.
   3. Adherence to post-approval requirements for exemptions as stated in D of this document.

1. Exempt Protocol Submission: Submission of an exemption request entails submitting a “Request for Exemption” application to the W&M IRB with appropriate materials. All applications must include the following materials:
   1. Consent information (use the appropriate W&M IRB consent template for exempt research)
   2. All stimuli, measures, and instruments (e.g.: surveys, interview protocols, focus group protocols, observation protocols, benign behavioral intervention protocols, taste test protocols)
   3. Any additional documentation required by the IRB office such as IRB required conditional procedures applicable to all W&M researchers
   4. Recruitment information such as email templates, phone scripts, social media posts, SONA descriptions, etc.
   5. Proof of human subjects research training completion for all research team members who recruit and consent participants, collect data from participants, implement the intervention with participants, or analyze private identifiable data used in the research project.
      • The lead PI is responsible for tracking undergraduate researchers and their training. The IRB application should be updated when students leave or join research protocols.
   6. Where applicable, exemption applications must also include:
      1. A NIH Data Management and Sharing Plan if the study is funded or supported by NIH
      2. When the research involves the use of “sensitive data,” an attestation that the researchers will work with W&M IT to ensure compliance with applicable laws and university policies. 
      3. Any relevant agreements such as a data use agreement
      4. An implemented “broad consent addendum” form used at primary data collection if the research team wishes to use secondary data from a project where “broad consent” was sought and given by participants
      5. Debriefing materials if deception or incomplete disclosure will occur in the study
      6. Forms sent to participants/guardians regarding recordings in classrooms.
      7. The HIPAA authorization form that was used/will be used with participants/guardians or the submission of a HIPAA waiver request form.
      8. The FERPA permission information used with participants and guardians (which can be integrated into the Consent process).
2. Exempt Protocol Approval: The IRB office will review and approve exemption requests in accordance with 45 CFR 46 and the W&M FLEX special exemption category as noted in this document. Once the IRB office approves a study as exempt, approval for the protocol does not expire. Modifications must be submitted in accordance with section D of this procedure. At initial approval, some exemption requests require the IRB to complete a “limited review” for issues related to participant privacy and confidentiality.
   1. A limited review is part of the federal regulations requiring that “there are adequate provisions to protect the privacy of participants and to maintain the confidentiality of data” for research studies qualifying for exemption.
   2. When conducting a limited review for studies eligible for exemption under 45 CFR 46(d)7, the IRB office must ensure that:
      1. adequate provisions to protect the privacy of participants and to maintain the confidentiality of data are in place;
      2. broad consent for storage, maintenance, and secondary research use of identifiable private information or identifiable biospecimens is obtained;
      3. broad consent is appropriately documented, or waiver of documentation is appropriate; and
      4. if there is a change made for research purposes in the way the identifiable private information or identifiable biospecimens are stored or maintained, there are adequate provisions to protect the privacy of participants and to maintain the confidentiality of data.
   3. At W&M, a limited review may be performed by an IRB board member. The following elements will be evaluated during a limited review: An assessment of the procedures and information shared with participants regarding their personal privacy during the implementation of research procedures and their confidentiality during data management.
      1. The IRB reviewer may require specific information to be disclosed to participants during the consent process.
      2. The IRB reviewer may require additional procedures be implemented to ensure adequate participant protections or disclosure
   4. Data sensitivity and classification
      1. Data classified by the IRB as sensitive may be associated with a study that is eligible for exemption. There are some situational exclusions.
      2. For all studies involving sensitive data, it is expected that the researcher will attest that the researchers will work with W&M IT to ensure compliance with applicable data laws and University policies.

1. All exempt protocols are subject to the W&M SOP for Amendments, Renewals, Transfers, and Closures.
2. Amendments to Exempt Protocols
   1. Protocol modifications that require an amendment to the approved exempt protocol:
      1. Change in engaged research personnel
      2. Addition of funding and/or subsequent changes in the project’s funding.
      3. Additions or changes to participant groups. Examples include addition of minors, pregnant people, incarcerated people, participant populations that are contextually vulnerable, or participant group(s)not initially described in the approved protocol.
      4. Addition or changes to data collection procedures. Examples include new surveys, interviews, or observations protocols or changes to existing surveys, interviews, or observation protocols.
      5. Addition of a dataset that requires a data use agreement, material transfer agreement, or addition of any identifiable or indirectly identifiable data that is not publicly available. For example, records may be subject to FERPA even if a member of the research team already has access to the data due to their role as an educator.
      6. Addition of any information that will be collected that directly links the participant to the study or the study data. For example, the collection of identifiable information to provide compensation to one or more participant
      7. Addition of audio or video recording of participants, use of photography, screen recording, and/or motion tracking.
      8. Addition of multimedia such as videos and/or images that participants will view.
      9. Addition or change to compensation.
      10. Addition or changes to any procedures that are physical in nature.
      11. Correction of documents beyond spelling, grammar, background pictures, or one-word replacements that do not affect the meaning of the sentence or study.
   2. Protocol modifications that do not require IRB approval for Exempt protocols
      1. Change in participant numbers if the change is no more or less than 10% of the approved amount listed in the IRB application and supporting documents.
      2. Minor editorial changes (such as punctuation, single word changes, or grammar) or re-ordering of questions
   3. Approval Renewal for Exemptions
      • Unless otherwise specified, research studies that qualify for an exemption do not require annual renewal. There may be exceptions based on study-specific contextual factors. Exempt studies will be assigned an “administrative check-in date” that serves as a reminder for the research team to review their protocol and ensure that no updates are needed.

1. People who are pregnant can be involved in all research categories eligible for exemption under both the 45 CFR 46 and the W&M FLEX special exemption category.
2. People who are incarcerated may only be involved in research eligible for exemption under both the 45 CFR 46 and the W&M FLEX special exemption category if the research is aimed at involving a broader participant population that only incidentally includes people who are incarcerated
3. People who are under the age of 18 years of age (or are legally considered a minor) have restrictions regarding involvement in research
   1. When subject to 45 CFR 46, minors may be involved in the following research procedures:
      1. Minors may be involved in research considered normal educational research in educational settings, under exemption category d.1.
      2. Minors may be involved in research involving observations for research purposes in public when the investigator(s) do not participate in the activities being observed, under category d.2.
      3. Minors may be involved in research use where secondary information is used as research data, under category d.4.
      4. Minors may be involved in research considered a taste and food quality evaluation and consumer acceptance, under category d.6.
      5. Minors may be involved in research including the storage, maintenance, and use of secondary research data when broad consent was initially sought and documented, under categories d.7 and d.8
   2. When subject to 45 CFR 46, minors may not be involved in the following research procedures:
      1. Minors may not be involved in research involving surveys, interviews, focus groups, or observations of private activities.
      2. Minors may not be involved in research involving surveys, interviews, focus groups, and observations of private activities. Minors may be observed for research purposes in public when the investigator(s) do not participate in the activities being observed.
      3. Minors may not be involved in research involving benign behavioral interventions. 
   3. When not subject to 45 CFR 46, the research may be reviewed under the William & Mary FLEX special exemption categories, allowing the use of the following procedures with minors:
      1. Surveys, interviews, and focus groups;
      2. Benign behavior interventions;
      3. Non-invasive collection of human body data such as weight measurement using a scale, height measurement using a tape measure, or tracking eye movement with an eye tracker;
      4. Use of secondary private identifiable/indirectly identifiable data for research.

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.

 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
• 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

Appendix A

Studies Eligible for Exemption under 45 CFR 46

 The sections below detail the exemption categories from 45 CFR 46 for minimal risk research activities. The W&M IRB makes all exemption determinations.

1. Exempt category d.1 includes research conducted in established or commonly accepted educational settings that involve normal educational practices that do not adversely influence students' opportunity to learn required educational content or the assessment of educators who provide instruction. This includes most research on regular and special education instructional strategies, and research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods.
   • The research procedures must take place in an established or commonly accepted educational setting and involve normal educational practices.
   • Researchers must justify how the proposed research setting qualifies as an “established” or “commonly accepted” educational setting and how the research activity is a “normal educational practice on behalf of educational agencies or institutions to develop, validate, or administer predictive tests; administer student aid programs; or improve instruction.”
   • Example settings: school, after school clubs, distance and online learning environments, conferences, study abroad programs, a place where formal training or learning occurs, and other settings deemed culturally appropriate for education and training to occur
   • Example activities: classroom observation, use of assessment/evaluation information, most action research, access to some FERPA data if developing or validating tests or instruction, professional development workshops, massive open online courses (MOOCs), and experiments with instructional design (as long as they are not radically innovative)
2. Exempt category d.2 is research that includes educational tests (cognitive, diagnostic, aptitude, achievement), surveys, interviews, or observation of public behavior (including visual or auditory recording) if at least one of the following criteria is met:
   • The information obtained is recorded by the investigator in such a manner that the identity of the human participants cannot readily be ascertained, directly or through identifiers linked to the participants.
   • Any disclosure of the research participants’ responses would not reasonably place the participants at risk of criminal or civil liability or be damaging to the participants' financial standing, employability, educational advancement, or reputation.
   • Readily ascertainable: if the data are directly identifiable linked to a master list that the researcher(s) can access, indirectly identifiable to anyone on the research team where an individual can be identified from the data due to researcher(s) access, role, or expertise, or participant can be identified from the content of data, triangulation of data content, pairing the research data with other data, or participant group/subgroup size
   • The information obtained is recorded by the investigator in such a manner that the identity of the participants can readily be ascertained, directly or through identifiers linked to the participants, and an IRB conducts a limited IRB review.
3. Exempt category d.3 is research involving benign behavioral interventions in conjunction with the collection of information from an adult participant through verbal or written responses (including data entry) or audiovisual recording if the participant prospectively agrees to the intervention and information collection and at least one of the following criteria is met:
   1. The information obtained is recorded by the investigator in such a manner that the identity of the human participants cannot readily be ascertained, directly or through identifiers linked to the participants;
   2. Any disclosure of the participants’ responses would not reasonably place the participants at risk of criminal or civil liability or be damaging to the participants' financial standing, employability, educational advancement, or reputation;
   3. The information obtained is recorded by the investigator in such a manner that the identity of the human participants can readily be ascertained, directly or through identifiers linked to the participants, and an IRB conducts a limited IRB review;
   4. If the research involves deceiving the participants (including leaving out pertinent information) regarding the nature or purposes of the research, in order for the study to be eligible for exemption, the participant must prospectively agree (via consent) to participate in research where they will be unaware of or misled regarding the nature or purposes of the research.
4. Exempt category d.4 is secondary data research for which consent is not required: Secondary research uses identifiable private information and/or identifiable biospecimens when at least one of the following criteria is met:
   1. The identifiable private information and/or biospecimens are publicly available;
   2. Information, which may include information about biospecimens, is recorded by the investigator in such a manner that the identity of the human participants cannot readily be ascertained directly or through identifiers linked to the participants, the investigator does not contact the participants, and the investigator will not re-identify participants;
   3. The research involves only information collection and analysis involving the investigator's use of identifiable health information when that use is regulated under HIPAA.
   4. This identifiable private data is considered under W&M data categorization as either “protected” or “sensitive” data for which a data access and security plan must be submitted with the exemption application.
   5. If the data are a “limited data set” under HIPAA, a data use agreement (DUA) is likely required by the data provider, and it must be uploaded to the exemption application.
   6. If the data are covered under HIPAA and identifiable as defined by HIPAA, a Business Associate’s Agreement (BAA) is likely required by the data provider and it must be uploaded to the exemption application.
5. Exemption category d.5 is a review category rarely used at W&M because it includes “research and demonstration projects conducted or supported by a federal department or agency, or otherwise subject to the approval of department or agency heads […] and are designed to study, evaluate, improve, or otherwise examine public benefit or service programs, including procedures for obtaining benefits or services under those programs, possible changes in or alternatives to those programs or procedures, or possible changes in methods or levels of payment for benefits or services under those programs.”
6. Exemption category d.6 are studies on taste and food quality evaluation and consumer acceptance studies if they include:
   1. Consumption of wholesome foods without additives or
   2. Consumption of a food that contains a food ingredient at or below the level and for a use found to be safe, or agricultural chemical or environmental contaminant at or below the level found to be safe, by the Food and Drug Administration or approved by the Environmental Protection Agency or the Food Safety and Inspection Service of the U.S. Department of Agriculture.
7. Exemption category d.7 for storage or maintenance for secondary research for which broad consent is required: Storage or maintenance of identifiable private information or identifiable biospecimens for potential secondary research use if an IRB conducts a limited IRB review
   • This review category allows for the storage and maintenance of private identifiable data or biospecimens.
   • A limited review must be completed by the IRB for this category to be used.
8. Exemption Category d.8 for secondary research for which broad consent is required: Research involving the use of identifiable private information or identifiable biospecimens for secondary research use, if the following criteria are met:
   1. Broad consent for the storage, maintenance, and future use of the identifiable private information or identifiable biospecimens was previously obtained;
   2. Documentation of informed consent or a full waiver of documentation of consent was previously obtained;
   3. An IRB conducts a limited IRB review and makes the determination that the research to be conducted is within the scope of the broad consent; and
   4. The investigator does not include returning individual research results to subjects as part of the study plan. This provision does not prohibit an investigator from complying with legal requirements to return individual research results.

Procedure 3: Expedited Review of Human Subjects Research

Scope & Purpose: This procedure applies to all faculty, staff, students, and affiliated researchers, working within the scope of their roles at William & Mary, to complete human subjects research that is overseen by the Institutional Review Board (IRB). The purpose of this procedure is to detail William & Mary’s procedure to address the IRB’s standard and operating practices for the conduct of expedited reviews. This document outlines the processes of preparing, conducting, and documenting expedited reviews.

Effective Date: 04 April 2026

Responsible Office: Office of the Vice Provost for Research

Last Updated: 03 August 2026

II. Definitions

1. Children: Children are defined in the HHS regulations as persons who have not obtained the legal age for consent to treatments or procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted. 45 CFR 46.402(a).
2. Criteria for Approval: The criteria detailed in 45 CFR 46.111 address qualities of a human subjects research protocol that are eligible for approval. These criteria must be met for all human subjects research where 45 CFR 46 is applied.
3. Expedited Review: A list of categories of research that may be reviewed by the IRB through an expedited review procedure. Expedited review procedures are for certain kinds of research involving no more than minimal risk, and minor changes in IRB Full Board approved research.
4. Identifiable Private Information: Identifiable private information is private data for which the identity of the participant is or may readily be ascertained by the investigator or associated with the information. Private information includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information that has been provided for specific purposes by an individual and that the individual can reasonably expect will not be made public.
5. Identifiable Biospecimen: Identifiable biospecimen is a natural sample for which the identity of the participant is or may readily be ascertained by the investigator or associated with the sample data.
6. Informed Consent: The informed consent process involves three key features: (1) disclosing to potential research participants’ information needed to make an informed decision; (2) facilitating the understanding of what has been disclosed; and (3) promoting the voluntariness of the decision about whether or not to participate in the research. Informed consent must be legally effective and prospectively obtained. Requirements for Informed Consent are detailed in 45 CFR 46.116.
7. Minimal Risk: Minimal risk is the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.
8. More than Minimal Risk: More than minimal risk are situations where the probability and magnitude of harm or discomfort anticipated in the research are greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.
9. Pregnant: Pregnancy encompasses the period from implantation until delivery. A person shall be assumed to be pregnant if they exhibit any of the pertinent presumptive signs of pregnancy, such as missed menses, until the results of a pregnancy test are negative or until delivery.
10. Prisoners: A person who is incarcerated is any individual involuntarily confined or detained in a penal institution. The term is intended to encompass individuals sentenced to such an institution under a criminal or civil statute, individuals detained in other facilities by virtue of statutes or commitment procedures which provide alternatives to criminal prosecution or incarceration in a penal institution, and individuals detained pending arraignment, trial, or sentencing. Individuals who are incarcerated if they are in any kind of penal institution, such as a prison, jail, or juvenile offender facility, and their ability to leave the institution is restricted. People who are incarcerated may be convicted of a crime or may be untried persons who are detained pending judicial action, for example, arraignment or trial.
11. Subparts: Subparts are sections of 45 CFR 46 with additional information and requirements. In the case of human subjects research regulations, subparts identify some vulnerable populations (pregnant people, fetuses, neonates, those who are incarcerated, and minors) that require additional protections in research.
12. Vulnerable Populations: Vulnerable populations are identified in the human subjects research regulations as pregnant people, fetuses, neonates, those who are incarcerated, minors, individuals with impaired decision-making capacity, and economically or educationally disadvantaged persons. The IRB may also require additional protections for any other group not specified in the regulations but determined, by the IRB, to be vulnerable.

III. Procedure

All William & Mary researchers conducting human subjects research are expected to submit an IRB protocol to the IRB for review and approval before implementation, including study protocols eligible for expedited review. 

IRB members will conduct initial reviews, continuing reviews for annual approval renewal where applicable, and amendments as applicable for all non-exempt, minimal risk research eligible for review via the expedited procedures as outlined in 45 CFR 46.

Expedited review is appropriate when the proposed research poses no more than minimal risk to participants, and study procedures involve only one (or several) of the categories of research outlined by 45 CFR 46 and supplemental guidance. These categories are maintained by the Secretary of Health and Human Services (HHS), updated as appropriate, and posted as a notice in the Federal Register.

1. When obligated to apply 45 CFR 46 to an IRB protocol, the IRB Chair (or their designee(s) will conduct an expedited review for minimal risk research eligible under 45 CFR 46 and the William & Mary Policy, including this standard.
2. All requirements from 45 CFR 46 are applicable when human subjects research is eligible for Expedited review and the research is:
   1. Subject to the DoD, USDA, FDA regulations, or other signatories of the Common Rule,
   2. Sponsored or Funded,
   3. Contractually Obligated,
   4. Associated with an Agreement, or
   5. Cooperative
3. When not obligated to apply 45 CFR 46 to an IRB protocol, the IRB Chair (or their designee(s)) will either conduct an expedited review for minimal risk research eligible under 45 CFR 46, or they will determine the research is eligible for W&M’s FLEX exemption category in accordance with the procedure for exempt research and this procedure.
4. When 45 CFR 46 applies, research activities should not be deemed to be “of minimal risk” because they are included on the list maintained by the Secretary of HHS. Inclusion on this list means that the activity is eligible for review through the expedited review procedure when the specific circumstances of the proposed research involve no more than minimal risk to human participants.
5. When 45 CFR 46 applies, the categories on this list apply regardless of the age of participants, except as noted by the Secretary of HHS.
6. When 45 CFR 46 applies, the expedited review procedure may not be used where identification of the participants and/or their responses would reasonably place participants at risk of criminal or civil liability or be damaging to the participants' financial standing, employability, insurability, reputation, or be stigmatizing, unless reasonable and appropriate protections will be implemented so that risks related to invasion of privacy and breach of confidentiality are no greater than minimal risk.
7. The expedited review procedure may not be used for classified human subjects research.
8. The standard requirements for informed consent found at 45 CFR 46.116 (or its waiver, alteration, or exception) and the Criteria for Approval found at 45 CFR 46.111 apply to research reviewed via expedited procedures.

B. Expedited Review Process

An expedited review procedure consists of reviewing human subjects research by either the IRB chairperson or by one or more reviewers from among members of the IRB:

1. The IRB members conducting the expedited review may exercise all the authority of the IRB except that the reviewers may not disapprove the research. The reviewers shall refer any research project, which the reviewer would have disapproved, to the convened IRB for review.
2. The reviewer may also refer other research activities to the convened IRB whenever the reviewer believes that Full IRB review is warranted.
3. The reviewer must apply all Criteria for Approval as outlined in 45 CFR 46 to approve any human subjects research with via expedited procedures.
4. Full Board Notification of Expedited Study Approval
5. When the expedited review procedures are used, the IRB office shall inform the IRB members of research projects that have been approved using expedited procedures.
6. Notification includes sharing the study title, PI, date of approval, and expedited approval category at a convened IRB committee meeting.

All required materials must be submitted to the IRB through the electronic IRB application system. Once submitted, the IRB office staff prepares the application before sending it to an IRB member for expedited review. Once the expedited reviewer completes their review, they return it to the IRB office staff for processing. IRB staff serving as Full Board members may, with the permission of the IRB chairperson, review research protocols at the Expedited level.

1. At William & Mary, the IRB application is an electronic application that outlines all study activities involving research with human participants. The application is completed by the researcher and electronically submitted to the IRB.
2. The IRB application must include final supplemental documents when necessary. These documents include: 
   1. Recruitment materials intended to be seen or heard by potential participants. This includes but is not limited to recruitment messages, fliers, announcements, and talking points.
   2. Informed consent materials including adult participant consent forms, minor participant assent forms, parental permission forms for minor participation, and any letters/scripts where consent/assent/permission is addressed.
   3. Finalized data collection instruments and research protocols for interventions, interactions, or manipulations of a participant’s environment.
   4. When applicable, the supplemental documentation may include other applicable documents such as agreements, data management plans, letters of support, etc.

D. Expedited Review: Protocol Pre-Review

1. Once the application is submitted through the electronic system, the IRB office staff will perform a pre-review. This pre-review consists of reading through the application and supplemental documents for consistency, detail, step-by-step procedures, information required by regulations, and required legal information. The pre-review may require the IRB office staff to communicate with the researcher and return the protocol to the researcher for needed changes related to internal consistency, cohesiveness, adherence to applicable laws, regulations, and standards.
2. In some cases, a study may require additional ancillary review before IRB approval is granted. These may include reviews such as Conflict of Interest (COI), Export Control, Research Security, Institutional Biosafety Committee (IBC), Information Technology (IT), Local Context or Participant Context, Site Context, or other applicable reviews.

The designated IRB member completing the review of the study application makes a determination regarding approval based on the criteria for approval as detailed in 45 CFR 46.111. Possible outcomes of this review include:

1. Approve. The research, proposed modification to previously approved research, or some approval renewals is approved. The expedited reviewer has made the determinations required for approval (i.e., approval criteria and any applicable special determinations (e.g., waivers, alterations, vulnerable population determinations, etc.). No further action is needed.
2. Minor Stipulations Required. The proposed modification to the previously approved research is approved with conditions that must be satisfied before the approval is in effect. The reviewer communicates the stipulations required to meet the criteria for approval through comments made in the IRB system. The IRB office staff works with the researcher to process approval once the stipulations are verified.

For research previously approved by a convened IRB, the IRB may use the expedited review procedure to review minor changes in previously approved research in accordance with 45 CFR 46.110(b)(1)(ii) and the William & Mary IRB Human Subjects Research policy and applicable procedures.

1.  Renewal of full board studies that qualify for review under expedited category 8
   1. The research is permanently closed to the enrollment of new participants;
   2. All participants have completed all research-related interventions; and
   3. The research remains active only for long-term follow-up of participants.
      1. “Long-term follow-up” includes:
         1. Research interactions that involve no more than minimal risk to participants (e.g., quality of life surveys); and
         2. Collection of follow-up data from procedures or interventions that would have been done as part of routine clinical practice to monitor a participant for disease progression or recurrence, regardless of whether the procedures or interventions are described in the research protocol.
         3. Some research studies that are not eligible for expedited review under category (8)(a) at the time of renewal may be eligible for expedited review under one of the other expedited review categories.
         4. Where no participants have been enrolled and no additional risks have been identified:
            1. “No participants have been enrolled” means that no participants have ever been enrolled at a particular institution; and
            2. The criterion that “no additional risks have been identified” means that neither the investigator nor the IRB at a particular institution has identified any additional risks from any institution engaged in the research project or from any other relevant source since the IRB’s most recent prior review.
         5. Where the remaining research activities are limited to data analysis.
         6. An IRB may use an expedited review procedure to conduct review of a renewal request when the only remaining human participants research activity is the analysis of data that includes identifiable private information and the IRB chair or their designee determines that this activity involves no more than minimal risk.
            1. The process for conducting renewal approval of research under expedited review category 8 can be accomplished through an abbreviated process.
            2. Expedited category 8 does not apply when a research study continues to involve human participants where the investigators conducting the research continue to obtain:
               1. Data about the participants of the research through intervention or interaction with them; or
               2. Identifiable private information about the participants of the research.
                  1. For a multi-site research project, an expedited review procedure may be used by the reviewing IRB whenever the conditions of category 8 are satisfied for all sites involved
2. Full board studies that qualify for review under expedited category 9
   1. An expedited review procedure may be used for the continuing review of research for renewal approval and amendments for previously approved research by the convened IRB if the study meets all the following conditions:
   2. The research is not conducted under an investigational new drug application (IND) or an investigational device exemption (IDE);
   3. Expedited review categories (2) through (8) do not apply to the research; and
   4. The convened IRB has determined and documented that the research involves no greater than minimal risk to the participants:
   5. The convened IRB must have determined that either the research project involved no more than minimal risk, or the remaining research activities involving human participants present no more than minimal risk to the participants.
      1. This determination could occur as early as the convened IRB meeting at which the IRB conducted its initial review.
      2. No additional risks or issues with the research have been identified.
      3. When a full board study is initially approved, a majority of the quorum vote that the study can be reviewed via expedited category 9.
         1. All amendments to a full board study where a category 9 vote took place, are eligible for expedited review, unless they increase risk to participants or are outside of the limits described in the Expedited categories. These studies may be approved via expedited procedures where the reviewer is the IRB Chair or their designee.
         2. All approval renewal requests for full board studies where a category 9 took place are eligible for expedited review and may be approved via expedited procedures where no information shared during the renewal process indicates an increase in risk to participants or where the history of the study implementation suggests issues with study management.

Approval renewal for studies approved at the Expedited level do not undergo the annual renewal unless the IRB reviewer has documented the determination that it must undergo renewal approval.

A study reviewed via expedited procedures would undergo renewal approval if the risks/benefits of the study are likely to change based on the implementation of procedures, issues with researcher’s compliance or history of ethical practices, the role technology may play in the research, considerations regarding genomics, and contractual or sponsor obligations. Refer to the IRB’s unit standard for renewals, amendments, closures, and transfers.

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 SubjectsWilliam & 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

Procedure 4: Review and Approval for Clinical Trials

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.

Effective Date: 04 April 2026

Responsible Office: Office of the Vice Provost for Research

Last Updated: 03 August 2026

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.

 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.

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.

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.

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.

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

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.

• 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

•  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.

• 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.

Procedure 5: Conflicts of Interest, Conflicts of Commitment, Coercion, and Undue Influence in Human Subjects Research

Procedure 6: Full Board Meeting, Review, and Membership

Procedure 7: Renewals, Amendments, Closures, and Transfers

Procedure 8: Review and Approval for Cooperative Research

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 working within the scope of their roles at William & Mary (W&M) to complete human subjects research overseen by the W&M Institutional Review Board (IRB). The purpose of this procedure is to detail W&M’s process for addressing multi-site or cooperative human subjects research conducted by W&M researchers. In this document, you will find the policy and standard operating procedures for the use of reliance agreements and how the W&M IRB facilitates cooperative research The purpose of this procedure is to detail W&M’s procedure to address multi-site or cooperative research with human subjects completed by W&M researchers. In this document, you will find the policy and standard operating procedures for the use of reliance agreements and how the W&M IRB facilitates cooperative research.

II. Definitions

1. Cooperative Research: Cooperative research involves more than one institution. In the conduct of cooperative research projects, each institution is responsible for safeguarding the rights and welfare of human subjects and for complying with this policy. The institutional official (IO) is the individual who is legally authorized to act for each institution and, on behalf of the institution, obligates the institution to the terms of its Federalwide Assurance.
2. Federalwide Assurance (FWA): An FWA is the documentation of an institution’s commitment to comply with federal regulations and maintain policies and procedures for the protection of human participants. An institution must have an FWA to receive Department of Health & Human Services (DHHS) support for human subjects research. This is the principal mechanism for compliance oversight by the Office for Human Research Protections.
3. IRB of Record: The IRB of Record assumes primary responsibility for the review and approval of a study. Any IRB overseeing human subject protections for a study is considered an IRB of Record.
4. Multi-Site Study: A multi-site study is one that uses the same protocol to conduct non-exempt human research at more than one site.
5. Participating Site: In a multi-site study, a participating site is a domestic entity that will rely on the sIRB to carry out the site's IRB review of human research for the study.
6. Relying IRB: An IRB designated via an agreement to cede review to an external IRB for a particular study.
7. Single IRB: Single IRB is a process and a title. It is a process by which an IRB of record, selected on a study-by-study basis, provides the ethical review for all sites participating in a multi-site study. A single IRB is also a title and refers to an independent IRB or an IRB associated with an institution engaged in the multi-site study that serves as the “reviewing IRB” or “IRB of record” on the project. NIH refers to the single IRB as “sIRB.”

III. Procedure

W&M researchers engaging in cooperative research with another institution's IRB and/or external investigators must attach all applicable agreements to the protocol, including Institutional Authorization Agreements (IAAs), Individual Investigator Agreements (IIAs), and Acceptance of Exemption determinations. See Section B for details.

W&M researchers engaging in non-exempt federally funded human subjects research that is determined to be cooperative research as defined by the federal regulations at 45 CFR 46.114 must have their research reviewed and approved by a single IRB before human subjects research begins.

Cooperative research for which more than a single IRB review is required by law (including tribal law passed by the official governing body of an American Indian or Alaska Native tribe); or research for which any federal department or agency supporting or conducting the research determines and documents that the use of a single IRB is not appropriate for the particular context.

When Single IRB review applies, formal agreements will be used to establish the terms of cooperative review and approval.

For unfunded or privately sponsored non-exempt human subjects research, the W&M IRB will enter into agreements as appropriate. See Section B.4 for procedures applicable to research qualifying for an exemption determination.

1. A researcher must be “engaged in human subjects research” for the W&M IRB to consider entering into a reliance agreement for non-exempt research or providing an exemption determination acceptance letter for research eligible for exemption.
   1. The W&M IRB makes this determination regarding their own employees or agents acting on behalf of W&M
   2. The W&M IRB makes this determination regarding unaffiliated investigators engaged in research enacted by W&M
   3. The W&M IRB does not make this determination for individuals affiliated with another IRB.
2. The W&M IRB will make an “engaged in human subjects research” determination when their employees or agents, acting on behalf of the institution, for purposes of human subjects research project (regardless of approval level), obtain:
   1. the informed consent of human participants for research purposes*;
   2. data about the participants through intervention, interaction*, or manipulation of environment;
   3. identifiable or re-identifiable private data about the participants*; or
   4. a federal award through a grant, contract, or cooperative agreement for the non-exempt human subjects research, even where all activities involving human subjects are carried out by employees or agents of another institution.
3. “Employees and agents” are individuals who
   1. act on behalf of the institution; or
   2. exercise institutional authority or responsibility; or
   3. perform institutionally designated activities.
   4. “Employees and agents” can include staff, students, contractors, and volunteers, among others, regardless of whether the individual is receiving compensation.
4. Investigators from institutions engaged in the research retain responsibility for:
   1. overseeing protocol-related activities;
   2. ensuring the study interventions are administered in accordance with the IRB-approved protocol; and
   3. ensuring appropriate arrangements are made for reporting protocol-related information to investigators at other engaged institutions, including the reporting of safety monitoring data, noncompliance, unanticipated problems, and adverse events as required under the IRB-approved protocol; and

Based on the level of review or researcher affiliation, varying types of agreements or acknowledgments are available.

1. Requirements to Serve as the IRB of Record:
   1. The IRB of Record must hold a Federalwide Assurance (FWA) with the Office of Human Research Protections (OHRP) of the U.S. Department of Health and Human Services (HHS).
   2. The agreement must be signed by the institutional official or designee at each institution with an FWA
   3. The researcher may not serve as signatory on an agreement representing W&M.
2. Institutional Authorization Agreement (IAA)
   1. Institutional authorization agreement (IAA) is a type of agreement between two institutions with current FWAs. The IAA specifies an IRB of Record (i.e. reviewing IRB) and a relying IRB.
   2. An IAA is colloquially called a “Reliance Agreement”
   3. An IAA allows an institution with an IRB that holds an FWA to rely on the IRB review and approval from another institution that holds an FWA.
   4. IAAs can cover one project or multiple projects as described in the agreement itself.
   5. IAAs are signed by the institutional official at each institution or their designee with the delegated authority to sign such agreements.
   6. IAAs are not issued for exempt level research, including FLEX exemptions. Refer to section B.4 on letters of acceptance of exemption determinations.
3. Individual Investigator Agreement (IIA)
   1. An individual investigator agreement (IIA) is an agreement between W&M and a researcher who is not affiliated with an IRB that holds an FWA.
   2. An IIA binds the unaffiliated researcher to W&M’s rules and regulations regarding human subjects research.
   3. An IIA is signed by W&M’s institutional official, the W&M principal investigator (or their designee), and the individual unaffiliated researcher.
   4. IIAs are required for all both exempt and non-exempt human subjects research
   5. The W&M IRB can only serve as the IRB of Record when its agents (e.g., current faculty, staff, students) are engaged in the research within the defined scope of their role. IIAs are not issued for individuals external to William & Mary who wish to conduct their own research without a W&M researcher on the protocol.
4. Letter of Acceptance of Exemption Determination
   1. A letter of acceptance of an exemption determination is a letter from the W&M IRB. The letter indicates that the W&M IRB accepts the “exemption determination” of another IRB that holds an FWA.
   2. If another institution’s IRB has reviewed a study as exempt, the W&M IRB may accept this determination so that the exempt project does not undergo dual IRB review.
   3. The W&M IRB will provide their researchers with this letter if the researcher provides documentation to the W&M IRB that the reviewing IRB is aware that
      1. the W&M researcher is involved in the reviewed project, and
      2. all procedures carried out by the W&M researcher have been reviewed and approved by the reviewing IRB.
   4. W&M researchers must submit documentation to the W&M IRB if they wish to serve on exempt-level study that has/will be reviewed and approved by another IRB.
   5. If W&M IRB review and approves an exempt study with non-W&M collaborators, the approval from W&M IRB does not cover the collaborating researchers' activities. The collaborating researchers must contact their institution's IRB prior to beginning any work on the protocol.

1. Requesting an Institutional Authorization Agreement (IAA)
   1. An IAA can be submitted to the IRB office at the initial submission of the research protocol or during protocol review. The IAA can be reviewed concurrently with the review of the research project.
   2. An IAA can also be submitted after the protocol has been approved via a protocol modification request.
   3. Cooperative research cannot commence until after the IRB protocol is approved, and an IAA is signed by the institutional officials (or designees) from W&M and the relying institution(s).
   4. IAAs will not be executed for exempt level research, including FLEX exempt research. In rare circumstances, this may be waived.
2. Requesting an Individual Investigator Agreement (IIA)
   1. Requests for individual investigator agreements can be submitted to the IRB at the initial submission of the research protocol, during the review of the protocol, or after the protocol has been approved via an amendment request.
   2. All research activities carried out by the individual unaffiliated investigator must be detailed in the approved IRB protocol.
   3. Individual Investigators must provide proof of completion of applicable human subjects training.
   4. When executing the IIA, the individual investigators agree to adhere to all W&M ethical and compliant standards including requirements detailed in the IRB protocol.

1. Site context review, also known as local context review.
   1. The site context review furnishes the IRB of Record with all of the necessary information about human participants' protections and compliance at individual sites which enables the IRB of Record to make appropriate determinations.
   2. Site context review is completed by the relying IRB(s) and provided to the IRB of Record.
2. When W&M is the IRB of Record for Non-Exempt Research
   1. All research procedures, instruments, interventions, and materials that participants interact with must be provided to the W&M IRB for review and approval per IRB requirements for approval.
   2. All roles and responsibilities of the collaborating researchers must be detailed in the IRB protocol.
   3. All site context information from the cooperating sites or from the collaborating researchers must be provided to the W&M IRB for review and approval.
   4. When W&M serves as the reviewing IRB, it may review the entire research study, even if information about the entire study is not necessary to approve W&M’s part of the research.
   5. Site Context Review When W&M is the Reviewing IRB for a Reliance Agreement
      1. All relying IRBs must provide the necessary information to the W&M IRB:
         1. applicable state and local laws that may apply to the research
         2. all relevant conflict of interest information that is pertinent to the research being reviewed, including disclosures and any real or perceived conflicts of interest related to the proposed research project.
         3. all ancillary reviews required for the study to take place, such as institutional biosafety committee (IBC), radiation safety, institutional animal care and use committee (IACUC), health insurance portability and accountability act (HIPAA), export control, or other applicable reviews not otherwise specified
         4. proof of applicable, successful, and current human subjects research training completion for all members of the research team
3. When W&M is the Relying IRB for Non-Exempt Research
   1. The W&M IRB will provide the reviewing IRB with all necessary site context information or ancillary reviews.
   2. The W&M researchers will ensure that the reviewing IRB has all necessary information regarding human subjects research training and relevant COI information.
   3. When W&M is engaged in only part of a cooperative research project, the reviewing IRB must review and approve the part(s) of the research in which W&M is engaged.
   4. Site Context Review when W&M is the Relying IRB for a Reliance Agreement
      1. W&M IRB will provide the IRB of Record with the following information:
         1. applicable information relating to Virginia’s local and state laws that may apply to the research
         2. all relevant conflict of interest information that is pertinent to the research being reviewed, including disclosures and any real or perceived conflicts of interest related to the proposed research project
         3. all ancillary reviews required for the study to take place, such as institutional biosafety committee (IBC), radiation safety, institutional animal care and use committee (IACUC), export control
         4. proof of successful and current human subjects research training completion for all members of the research team
         5. any applicable W&M regulations, policies, or unit standards that are required for the study’s commencement
         6. all reasonable requests for information by the IRB of Record with the necessary information
4. When W&M is engaging in cooperative Exempt Research
   1. The W&M IRB may provide the W&M researchers with a letter detailing the IRB’s acceptance of another IRB’s exemption determination.
   2. The W&M researchers will ensure that the reviewing IRB has all necessary information regarding human subjects training and relevant COI information.
   3. All research procedures, instruments, interventions, and materials that participants interact with must be provided to the reviewing IRB, and the role of the W&M researchers must be clearly detailed.
   4. W&M researchers must provide the exemption determination letter and approved protocol to the W&M IRB for the exemption acceptance letter to be generated.
   5. For exempt cooperative research that includes W&M researchers and unaffiliated individual research collaborators, the W&M IRB will require the unaffiliated individual to complete an Individual Investigator Agreement detailed in B.3.

1. When hiring a service to assist with the implementation of the research internationally, there will likely be a contract or agreement such as a sub-award, sub-contract, service contract, MOU, between the individual or organization and W&M that details obligations such as scope of work and adherence to laws, policies, and other practices.
2. Institutions, hired contractors, enumerators, or volunteers do not need IRB approval through W&M and do not need an Individual Investigator Agreement (IIA) with the W&M IRB when:
   1. An individual is functioning within their regular work responsibilities and their involvement in the research is limited to those work responsibilities only, without further contribution to the research, then they are generally not considered study team members.
   2. The employees or agents perform commercial or other services for investigators provided that all of the following conditions also are met:
      1. the services performed do not merit professional recognition or publication privileges; and
      2. the services performed are typically performed by those personnel for non-research purposes; and
      3.  the institution’s employees or agents do not administer any study intervention being tested or evaluated in the study.
   3. Institutions whose employees or agents provide clinical trial-related medical services dictated by the protocol, and would typically be performed as part of routine clinical monitoring and/or follow-up of participants enrolled at a study site do not need IRB approval through W&M and do not need an Individual Investigator Agreement with the W&M IRB provided that all of the following conditions also are met:
      1. the institution’s employees or agents do not administer the study interventions being tested or evaluated under the protocol;
      2. the study-related services are typically provided by the institution;
      3. the institution’s employees or agents do not enroll participants or obtain the informed consent of any participant for participation in the research
   4. Institutions whose employees or agents administer the study interventions being tested or evaluated under the protocol limited to a one-time or short-term basis do not need IRB approval through W&M and do not need an Individual Investigator Agreement with the W&M IRB provided that all of the following conditions also are met:
      1. an investigator from an institution engaged in the research determines that it would be in the participant’s best interest to receive the study interventions being tested or evaluated under the protocol;
      2. the institution’s employees or agents do not enroll participants or obtain the informed consent of any participant for participation in the research
   5. Institutions do not need IRB approval through W&M and do not need an Individual Investigator Agreement with the W&M IRB when their employees or agents:
      1. inform prospective participants about the availability of the research;
      2. provide prospective participants with information about the research (which may include a copy of the relevant informed consent document and other IRB approved materials) but do not obtain participants’ consent for the research or act as representatives of the investigators;
      3. provide prospective participants with information about contacting investigators for information or enrollment; and/or
      4. seek or obtain the prospective participants’ permission for investigators to contact them.
   6. International institutions that permit use of their facilities for intervention or interaction with participants by investigators from another institution.

 F. Record Retention and Communication Among IRBs

1. When W&M is the Reviewing IRB (IRB of Record)
   1. Records must be retained and maintained for a minimum of five years and a maximum amount of time as required by the study procedures and applicable retention rules.
   2. Communication expectations for issues such as reportable events, renewals, amendments, personnel updates, consent posting requirements, expectations for post-approval monitoring, and how participant complaints are to be addressed must be included within the IRB application as procedures to be approved.
2. When W&M is the Relying IRB (not the IRB of Record)
   1. Records must be retained and maintained for a minimum of five years and a maximum amount of time as required by the study procedures.
   2. Communication expectations for issues such as reportable events, renewals, amendments, personnel updates, consent posting requirements, expectations for post-approval monitoring, and how participant complaints are to be addressed will be included as the reviewing institution requires

 G. National Institutes of Health (NIH) Multi-Site Studies

1. The use of a single IRB (sIRB) is required by NIH for all domestic sites of NIH-funded studies where each site will conduct the same protocol involving non-exempt human subjects research, whether supported by grants, cooperative agreements contracts, or the NIH Intramural Research Program.
2. Plans for the use of an sIRB must be included in all grant applications and contract proposals that are submitted to NIH.
3. This does not apply to foreign sites, career development, institutional training, or fellowship awards. The policy allows for exceptions in the following instances:
   1. Sites for which federal, state, or tribal laws, regulations, or policies require local IRB review.
   2. Other exceptions to allow for local IRB review may be considered by NIH based on compelling justification. These other exceptions must be reviewed and approved by NIH.
   3. The NIH sIRB policy allows the consideration of requests for other exceptions not based on a legal, regulatory, or policy requirement if there is a compelling justification for the exception. These other exceptions must be reviewed and approved by NIH.

1. No “Individual Investigator Agreement” will be associated with individuals who are “not engaged in human subjects research.”
   1. There will likely be a different contract or agreement such as a sub-award, sub-contract, service contract, MOU, between the individual or organization and W&M that details obligations such as scope of work and adherence to laws, policies, and other practices.
2. Institutions, hired contractors, enumerators, or volunteers are not engaged when:
   1. An individual is functioning within their regular work responsibilities and their involvement in the research is limited to those work responsibilities only, without further contribution to the research, then they are generally not considered study team members.
   2. The institution's employees or agents perform commercial or other services for investigators provided that all of the following conditions also are met:
      1. the services performed do not merit professional recognition or publication privileges;
      2. the services performed are typically performed by those personnel for non-research purposes; and
      3. the institution’s employees or agents do not administer any study intervention being tested or evaluated in the study.
3. Institutions (including private practices or individuals) that are not selected as a research site, whose employees or agents provide clinical trial-related medical services dictated by the protocol, and would typically be performed as part of routine clinical monitoring and/or follow-up of participants enrolled at a study site provided that all of the following conditions also are met:
   1. the institution’s employees or agents do not administer the study interventions being tested or evaluated under the protocol;
   2. the study-related services are typically provided by the institution;
   3. the institution’s employees or agents do not enroll participants or obtain the informed consent of any participant for participation in the research; and
   4. when appropriate, investigators from an institution engaged in the research retain responsibility for:
      1. overseeing protocol-related activities; and
      2. ensuring appropriate arrangements are made for reporting protocol-related data to investigators at an engaged institution, including the reporting of safety monitoring data and adverse events as required under the IRB-approved protocol.
4. Institutions (including private practices and individuals) not initially selected as a research site whose employees or agents administer the study interventions being tested or evaluated under the protocol limited to a one-time or short-term basis, provided that all of the following conditions also are met:
   1. an investigator from an institution engaged in the research determines that it would be in the participant’s best interest to receive the study interventions being tested or evaluated under the protocol;
   2. the institution’s employees or agents do not enroll participants or obtain the informed consent of any participant for participation in the research;
5. Institutions whose employees or agents:
   1. inform prospective participants about the availability of the research;
   2. provide prospective participants with information about the research (which may include a copy of the relevant informed consent document and other IRB approved materials) but do not obtain participants’ consent for the research or act as representatives of the investigators;
   3. provide prospective participants with information about contacting investigators for information or enrollment; and/or
   4. seek or obtain the prospective participants’ permission for investigators to contact them.
6. Institutions that permit use of their facilities for intervention or interaction with participants by investigators from another institution.
7. Institutions whose employees or agents release identifiable private information or identifiable biological specimens pertaining to the participants of the research.
8. Institutions whose employees or agents access or utilize individually identifiable private information only while visiting an institution that is engaged in the research, provided their research activities are overseen by the IRB of the institution that is engaged in the research
9. Institutions whose employees or agents author a paper, journal article, or presentation describing a human subjects research study.

 Footnotes

*Unless the individual is hired specifically for a commercial service; When hiring a service to assist with the implementation of the research internationally, there will likely be a contract or agreement such as a sub-award, sub-contract, service contract, MOU, between the individual or organization and W&M that details obligations such as scope of work and adherence to laws, policies, and other practices (ref. Section E).

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 policy and relevant law.

• OHRP: Engagement in Research with Human Subjects
• OHRP: Extending an FWA for Individual Investigators
• OHRP: Institutional Engagement in Research
• OHRP: Research Ethics video series: "Institutional Engagement in Research"
• Reliance Agreements
• Decision Chart of Engagement of Individuals

Appendix A

 The following are some examples, assuming the services described would not merit professional recognition or publication privileges:

• an appropriately qualified laboratory whose employees perform routine serum chemistry analyses of blood samples for investigators as a commercial service.
• a transcription company whose employees transcribe research study interviews as a commercial service.
• a hospital whose employees obtain blood through a blood draw or collect urine and provide such specimens to investigators as a service.
• a radiology clinic whose employees perform chest x-rays and send the results to investigators as a service.
• A survey firm if the above conditions are met, the firm typically performs surveys for non-research purposes, the firm is not administering any intervention, and the firm is not involved in obtaining the informed consent of human subjects for research

Procedure 9: Local and Participant Context Review

Under development

Procedure 10: Completing International Research with Human Subjects

Under development

Procedure 11: Human Subjects Research Involving Minors

Under development

Procedure 12: Research Involving People Who are Incarcerated

Under development

Procedure 13: Research with People Who are Pregnant and Neonates

Under development

Procedure 14: Unanticipated Problems and Adverse Events

Under development

Procedure 15: FDA Regulated Research, Medical Devices

Under development

Procedure 16: FDA Regulated Research, Drugs and Biologics

Under development

Procedure 17: Participant Concerns and Complaints

Under development

Procedure 18: Review and Approval for Pilot and Feasibility Work

Under development

Procedure 19: Informed Consent, Guardian Permission, Minor Assent, and Broad Consent

Under development