Find out more about the distinction between these two categories of research!

In order for a project to be subject to IRB review, it must meet the definition of “Human Subjects Research” (HSR). HSR can be broken down into two component parts: “research” and “human subjects.” Each of these terms have specific regulatory definitions. A project must meet BOTH definitions in order to be considered HSR, and therefore be subject to the regulations, including IRB review.

Only those projects which meet BOTH regulatory definitions of “research” and “human subjects” are subject to IRB review.

The first step in determining whether a project is HSR that requires IRB review or whether it is excluded is to determine if a project meets the definition of “research” according to the HSR regulations. 

Projects which meet the definition of “research” within the HSR regulations are considered to be human subjects research. Projects which do not meet the definition of “research” according to the HSR regulations may still be considered “research” in other contexts, but these projects are not human subjects research, under the HSR regulations. 

Research is defined in the HSR regulations (45 CFR 46.102(l)) as:

“A systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge.”

“Generalizable Knowledge” – A Clarification for Social/Behavioral/Educational (SBE) and Qualitative Research

The HSR regulations were written mainly with biomedical research in mind. The UNLV HRPP recognizes that the term “generalizable knowledge” is not necessarily the most appropriate term when referring to social/behavioral and educational (SBE) research, particularly research utilizing qualitative methodologies. 

However, while these research studies may not be strictly “generalizable” (a more appropriate term might include “transferrable”), these studies are often still seeking to contribute to an overall body or field of knowledge. In this way, the UNLV HRPP believes that the spirit of the regulations still applies to these kinds of research projects. 

So, when SBE/qualitative researchers consider whether their project meets the definition of (human subjects) “research,” they should consider the intentionality of their project: are you trying to add to, refine, or refute existing knowledge? Are you attempting to demonstrate the effectiveness of an intervention/process outside of your specific context and institution? Are you trying to make broad claims regarding a certain population or phenomenon? If the answer to any of these questions is yes, then your project is likely to meet the definition of (human subjects) “research” under the HSR regulations.

The HSR regulations include specific exceptions to the definition of (human subjects) “research.” These are specific kinds of activities that often include human subjects, but which the HSR regulations specifically consider to NOT be (human subjects) research. These kinds of projects are therefore not required to undergo IRB review. Each of these exceptions is discussed below.

This exclusion for scholarly and journalistic activities includes activities such as oral history, journalism, biography, literary criticism, legal research, and historical scholarship. These are activities that involve the collection and use of information, but which focus directly on the specific individuals about whom the information is collected.  For example, writing a biography of a living person would not be considered (human subjects) research under the HSR regulations and would not be subject to IRB review, because such an activity meets the exclusion category for “scholarly and journalistic activities.”

This exclusion is for activities conducted, supported, requested, ordered, required, or authorized by a public health authority. A “public health authority” is defined as “an agency or authority of the United States, a state, a territory, a political subdivision of a state or territory, an Indian tribe, or a foreign government … that is responsible for public health matters as part of its official mandate.” For example, the CDC would be considered a “public health authority.”

This exclusion applies only to activities that are limited to “those necessary to allow a public health authority to identify, monitor, assess, or investigate potential public health signals, onsets of disease outbreaks, or conditions of public health importance … Such activities include those associated with providing timely situational awareness and priority setting during the course of an event or crisis that threatens public health (including natural or man-made disasters).”

So, in order to fall under this exception, a project must be limited in scope to identify, monitor, assess, or investigate public health concerns, AND must be specifically authorized by a public health authority. 

A great example of this exception in action is COVID contact tracing. COVID contact tracing is often initiated and conducted by public health authorities, and is limited in scope to tracking and managing the spread of the disease. These projects do not require IRB review, as they fall under this specific exception to the definition of (human subjects) research.

This exception refers exclusively to activities performed by or for a criminal justice agency for activities authorized by law or court order solely for criminal justice or criminal investigative purposes. So, for example, collecting DNA samples from suspects in a criminal case, for the purposes of DNA testing within the context of a criminal justice investigation. These activities are excluded from the definition of (human subjects) research under the HSR regulations, and therefore are not subject to IRB review.

This exception refers exclusively to authorized operational activities (as determined by each agency) in support of intelligence, homeland security, defense, or other national security missions.

Quality Improvement/Assessment/Assurance Activities

Quality Improvement (also called Quality Assessment, Quality Assurance, Program Evaluation, etc.) activities are not addressed specifically in the text of the regulations along with the other exceptions from the definition of (human subjects) research in the HSR regulations. However, Quality Improvement (QI) activities generally do not meet the definition of (human subjects) “research,” due to the fact that QI activities are often not generalizable. 

A whole article could be dedicated to QI alone, so this article will not get into too much detail on this topic. Just be aware that the Office of Human Research Protections (OHRP) offers guidance on this topic.

Projects that are considered “excluded” are projects which are not subject to IRB review, usually because they do not meet the definition of (human subjects) research according to the HSR regulations, and occasionally because they do not meet the definition of “human subjects.” 

Regardless of the reason why the definition of “human subjects research” is not met, excluded projects are projects that are not subject to IRB review. IRB review is not required because the project does not meet the definition of (human subjects) “research” (and/or does not meet the definition of “human subject”).

What Does it Mean for a Project to be “Exempt”? What is the Difference Between “Excluded” and “Exempt”?

So what is the difference between projects that are “exempt” versus projects that are “excluded”? The key is in understanding what “exempt” means in the context of the HSR regulations.

What Does it Mean for a Project to be “Exempt”?

IRB review is divided into three levels of review, and the level of oversight a project receives from the IRB is directly proportional to the level of risk involved in a project.

Imagine a continuum where risk increases as you move from bottom to top. At the bottom of the spectrum, there is “exempt” review. Exempt review is reserved for the least risky studies, and receives the least amount of oversight. 

In the middle, there is “expedited” or “single reviewer” review. This review level is reserved for moderately risky studies, and receives a moderate level of oversight. 

At the top of the spectrum is full board or full committee review. This level of review is reserved for the riskiest studies, and provides the greatest amount of oversight. 

The main distinction between full board/full committee review and the other two, lower levels of review is that exempt and expedited/single reviewer review is allowed only for projects that are “minimal risk.” Full board/full committee review is used for projects that are greater than minimal risk.

So what exactly does “exempt” mean in this context? Technically, the “exempt” in “exempt review” means “exempt from the regulations.” Exempt research represents classes of research activities that we have agreed are low enough risk that the full set of regulations do not need to be applied to those projects. So, technically, institutions are not required to apply the regulations to exempt research projects, meaning that IRB review is not strictly required for exempt research projects.

However, institutions can, and often do, implement requirements that go above and beyond the regulations. These institutional requirements often include a requirement to submit exempt research projects for some kind of IRB review and approval. UNLV is one such institution. At UNLV investigators may not conduct exempt research until the project has been reviewed and approved by the IRB.

On a strictly technical level, the key difference between exempt HSR and excluded research is that excluded projects are projects that are NOT human subjects research, and therefore do not require IRB review. Exempt projects, on the other hand, are projects that ARE human subjects research, but are exempt from the regulations, including the requirement for IRB review. 

So the key is that excluded research does not require IRB review because the project is not human subjects research at all. Whereas exempt research projects ARE human subjects research, but may or may not be subject to the requirement for IRB review. This is because, while they ARE human subjects research, the risk level of the research is low enough that we have agreed that the research project can be exempt from the regulations, including the requirement for IRB review.

HOWEVER, it is crucial to understand that UNLV does require IRB review for exempt research. There are a few reasons for this, including the fact that the UNLV HRPP is accredited by the Association for the Accreditation of Human Research Protection Programs (AAHRPP), which requires accredited institutions to implement procedures for reviewing and approving exempt research. 

In addition, the regulations require, for some types of exempt research, a “Limited IRB Review.” Limited IRB review consists of verifying certain standards are met for exempt research that collects identifiable, sensitive information. Such standards include adequate privacy and confidentiality protections. The UNLV IRB achieves the Limited IRB review requirement through its process for reviewing and approving exempt research.

Since excluded projects do not require IRB review, investigators can conduct excluded projects without consulting the IRB. However, the UNLV IRB can make determinations and provide official determination letters from the IRB, which state that the project is excluded, and therefore not subject to IRB review requirements. 

Submitting for an official excluded determination is not required by UNLV. However, it may be desirable to obtain an official determination, as many journals and conferences request such documentation along with submitted presentations/articles.

To receive an official UNLV determination that a project is excluded, the investigator must create a submission in Cayuse, and when prompted, indicate that a project does not meet the definitions of “research” and/or “human subjects.” When this is done, the Cayuse form displays form fields where the investigator should explain why the project does not meet the definition of “research” and/or “human subjects.”

Investigators who are conducting exempt research must use the usual submission process for all HSR projects, using the electronic submission system, Cayuse. When prompted, indicate that the project DOES meet the definition of “research” AND “human subjects.” When that is done, Cayuse populates the usual IRB submission form fields.

Resources for Distinguishing Between Excluded and Exempt HSR

The UNLV HRPP offers resources to assist investigators in determining if their project is excluded, exempt, or some other level of IRB review.

UNLV Resources:

• UNLV IRB Standard Operating Procedure 5.02: Determination of Activities that Require IRB Review
• UNLV IRB Special Topics: Classroom Projects

OHRP Resources:

• Human research decision trees
  • Charts 02-08 assist in determining exemption and exempt category(ies)
• Quality Improvement FAQ Guidance