Is it Human Subjects Research (HSR) under IRB Regulations?

Summary

This document provides information regarding the federal definition of “human subject” and what activities involving humans are regulated by the IRB.

Full Description

An activity may be research and involve humans but not meet the criteria for regulated research with human subjects as defined by 45 CFR 46 (opens new webpage), which govern research with human subjects in the United States. 

William & Mary applies the federal definition of “human subject” to all protocols, regardless of funding.

Regulatory Definition of "Human Subject" 

“Human subject” (as defined by 45 CFR 46) is a living individual about whom an investigator (whether professional or student) conducting research: 

• Obtains information or biospecimens through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens; or   
• Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens.  
• The IRB does not regulate the use of identifiable or re-identifiable public data, if that public data has always been public.  
• The IRB does not regulate the use of secondary anonymous information or secondary information that has been de-identified by someone else before the researchers access the information as data for research. 

Note: "Human subject" and "participant" are used interchangeably across W&M IRB guidance documents, procedures and policies. When used in the context of IRB-regulated research, both are referring to the same definition.

Breaking Down the Definition of “Human Subject: 

1. "Living Individual: The data obtained, used, studied, analyzed, or generated must be about a live person. The data can be about a primary participant or a third-party participant.  
   • Primary participants: Individuals in the research project where the data generated or accessed is directly about their own thoughts, feelings, opinions, experiences, habits, physical/intellectual reactions, or biodata. 
   • Third-party participants: Individuals whom researchers do not directly interact with, but information about them is revealed or shared throughout the research process.  
     • Researchers must evaluate how the study’s design and procedures may impact third‑party participants and ensure that appropriate protections are in place to safeguard them. Third-party participants often are involved when methods such as photovoice, interviews, or genomic analysis are part of the study design. are used, as well as genomic research.  
     • The identifiable nature of the information about the third-party shared when compiled with the sensitivity of the data will directly affect the risk assessment. 
     • Examples include: 
       • When a primary participant discusses someone else in an interview, survey, or focus group, the person they are referring to is considered a third-party participant and must be considered as a participant during the IRB review process where risks/benefits analysis is made.   
       • When biospecimens or information from a deceased person are used to generate information about living people, such as their biological family. 
2. About Whom” can be interpreted to refer to:  
   • A person’s physical nature or physical responses
   • A person’s thoughts, feelings, reactions, habits, choices, opinions, and experiences 
   • Information or facts about a person’s private life 
   • A person’s performance or checks in ability or understanding 
3. 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 (e.g., a medical record).  
   • Identifiable private information is private information for which the identity of the subject is or may readily be ascertained by the investigator or associated with the information. 
   • An identifiable biospecimen is a biospecimen for which the identity of the subject is or may readily be ascertained by the investigator or associated with the biospecimen. 
   • Please refer to guidance regarding data and the nature of identifiability (opens new webpage).
   • Other laws and regulations may apply to this, such as FERPA, HIPAA, GDPR, etc. 
4. Intervention includes both physical procedures by which information or biospecimens are gathered (e.g., venipuncture) and manipulations of the subject or the subject's environment that are performed for research purposes.
   • Examples of Interventions:  
     • Behavioral interventions such as a computer game, changes in curriculum, change in clothing, changes in interior/exterior design that affect how people interact with a space   
     • Collection of biospecimens  
     • Use of a device or drug affecting the human body 
     • Manipulation of the environment such as changing a person’s environment to see what happens or changing their environment in a way that exposes them to or increases risks to which they would not otherwise be exposed. This may include observations. 
     • Request participants to put items in their home space for research purposes (when they otherwise would not). 
     • Recording a person or their environment for research purposes. Refer to W&M’s guidance on recordings for research purposes (opens new webpage).  
5. Interaction includes verbal, non-verbal, and written communication between investigator and subject. This includes potential participants (i.e. recruitment).
   • Examples of an “interaction:”  
     • Implementation of a survey, interview, or focus group 
     • Observation of participants
     • Recruitment processes or consent processes 

Office for Human Protections (OHRP) vs. William & Mary  

The Office for Human Research Protections (OHRP) only regulates human subjects research funded by the federal government. Funding agencies and signatories of the “Common Rule” (aka the regulations governing research with humans, 45 CFR 46 (opens new webpage)). Researchers receiving federal money must adhere to OHRP’s standards; however, institutions are permitted to apply the federal regulations to additional projects.  

W&M’s policy for research with human subjects applies the federal definitions of “research,” “human subject,” and “engagement” to all IRB protocols. When a project is federally funded, part of a cooperative agreement, regulated by the FDA, contractually required to follow federal regulations, or designated by the convened full IRB, the IRB Chair, or the Chair’s designee, the full federal regulations (45 CFR 46) apply to the research (W&M Human Research Policy).  

OHRP determines what needs to be regulated by asking: 

• Is the project federally funded? 
• Is the project “research,” as defined by the regulations? 
• Is the project “human subjects’ research,” as defined by the regulations? 

If the answers to the above questions (in order) are “yes,” then OHRP requires review of the project by an IRB before implementation. 

William & Mary’s IRB determines what needs to be regulated by asking:

• Is the project "research" (opens new webpage) as defined by the regulations? 
• Is the project “human subjects research” as defined by the regulations? 
• Is William & Mary “engaged” (opens new webpage) in the research? (I.e., someone associated with the research team is acting as an agent of W&M such as a faculty, staff, or student, and the research is within the scope of their appointed role at W&M.) 

If the answers to the above questions are all “yes,” then the researcher must seek IRB review and approval of the project before implementation. 

Regulated “human subjects research” projects that require IRB approval 

• Due to OHRP Regulations and the W&M policy (opens new webpage) for research with human subjects 
  • Any federally funded non-exempt research involving human subjects. 
  • Projects where researchers receive an award through a grant, contract, or cooperative agreement directly from HHS for the non-exempt human subjects research (i.e. awardee institutions), even where all activities involving human subjects are carried out by employees or agents of another institution.  
    • This requires the execution of a reliance agreement (opens new webpage) among IRBs.  
  • Researchers that obtain identifiable private information or identifiable biological specimens from any source for the proposed research. 
• Due to W&M policy for research with human subjects and IRB Convened Full Board Determination: 
  • Any research with humans regardless of funding source or IRB review level.
    • This includes research activities such as recruitment and consent, data collection, implementation of an intervention, manipulation of a participant’s environment, or access or analysis of identifiable/re-identifiable data.  
  • Manipulation of participants’ environment or experiences where the data generated is not about the participant specifically, but instead the human is used as a tool for data collection where the study could not be carried out without their participation and something unique about the individual may affect the study procedures or data.  
    • Example: Collection of samples from private property, such as well water and soil. This is most often considered human subjects research because the data collected about the property could either reveal information about an individual or affect the participants’ welfare, reputation, or have financial consequences.  
      • This can be considered human subjects research and it can also not be considered human subjects research and it would depend on the study design, role of participant, private/public nature of the property and the risks/benefits ratio of the research to the participant. 
    • Example: Implementation of citizen science projects where the people are both acting as a researcher of sorts, and also collecting data about themselves or they are manipulating their own environment for the sake of research.  This includes having participants bring items from the outside environment into their home environment such as putting samples and specimens in the refrigerator.  

Projects that are "Not Human Subjects Research (NHSR)"

The following projects are not considered research involving human subjects and as a result, do not require IRB approval:

• When humans administer medicine to animals for animal research except when  
  • There are any procedures that involve the human such as a survey or collection of demographics about the human, this will require IRB approval 
  • The research question is about humans and not necessarily the animals, this will require IRB approval.  
• Biospecimens obtained from another source (not directly from the participant) that is: 
  • either/totally anonymous and unlinkable to the person who it was obtained from or
  • is coded such that the researcher obtaining the sample does not know who it belongs to AND  a confidentiality agreement assures the researcher cannot learn the identity of the person who the sample was obtained from.  
  • This includes the research team members inability, through design and choice, to re-identify any individual through any data combination and analysis techniques.  
• Data from another source (not directly from a participant or their records) that is either:  
  • totally anonymous and unlinkable to the person who it was obtained from or  
  • is coded such that the researcher obtaining the data does not know who it belongs to AND  a confidentiality agreement assures the researcher cannot learn the identity of the person who the data was obtained from.

Appendix A 

“Humans As Tools” in Research - Questions for Consideration for Determination 

IRB Determination Flow Chart (PDF) 

1. What are the research questions for this project? 
2. What are the data collection methods for this project? 
3. What will the humans be doing in this study? 
4. Will any of the data points collected be about:
   • The human’s thoughts, feelings, experiences, habits, or beliefs? 
   • The human’s physical reactions or physiology?
   • The human’s environment and how they interact with it or how it affects them? 
   • Private facts about the person? 
5. Will this study influence or manipulate the human’s environment? 
6. Will the data collection method that the human is involved in pose the human any risk? If so, describe. 

IRB Considerations: Human Factors and Environment 

Identify the role of the humans in the research. (Are they participants, researchers, data collection agents, or other?)

• Human Subjects Involvement: 
  • Is this about a living individual or a living third party?  
  • Is the data obtained through interaction or intervention (physical procedures, manipulation of environment, communication or contact)? 
  • Does the research affect the human’s environment in any way? If so, how. 
  • Is the data identifiable? 
  • What are the participants' privacy expectations? 

Appendix B

When it’s NHSR but there are Ethical Obligations and What to Communicate to People 

If you are completing research activities that involve humans, but it has been determined that the IRB cannot review or approve the protocol because it does not meet the definition for research or human subjects research, you may still have ethical obligations around transparency and communication. In addition to this guidance, please refer to the guidance documents, Class Projects that are Not IRB-Regulated Research” and “Oral Histories and the W&M IRB” (opens to new webpages). 

Ethically, you are obligated to communicate all possible foreseeable risks to participants so that they can make an informed choice about their participation. This should include:  

• A discussion of what the worst-case scenario would be and the likelihood of that occurring due to your research design and risk mitigation strategies.  
• A discussion regarding any type of compensation or limits related to that compensation  
• In your research design, you should scientifically justify your inclusion/exclusion criteria and communicate those criteria to participants.  
• A discussion around proper procedures, safety precautions, emergency procedures, reporting obligations, etc.  

The IRB suggests that you create an information sheet and provide it to people who choose to help you with your research project. This form should be written at a 4th-6th grade level and include: 

• Contact information for the W&M team implementing the project 
• Description of all procedures and expectations related to the procedures  
• Description of how the information from the project will be used, protected, and reported including information about identifiable data.  
• Information about compensation and limits  
• Detailed information about risks as related to the procedures and any mitigating circumstances related to the risks  
• Additional resources as available or alternatives available  
• Information about any applicable laws that may be relevant to the activity  

The IRB suggests that you work with your department and the office of general counsel as appropriate when creating these forms or information that will be shared.