Defining Human Subject Research

Gathering Cultural Oral Histories from Local Native Americans

Human subject research conducted at PNNL covers a broad and diverse range of activities, and determining when those activities meet the federal definition of human subject research is not always easy or straightforward. Only qualified individuals may make this decision and, subsequently, the determination as to whether or not the activity qualifies for exempt review. At PNNL, this authority resides solely with the Institutional Review Board (IRB). Investigators should contact the IRB as early as possible in the process to make this determination.

"Research involving human subjects" means any activity that either:

Meets the DHHS definition of "research" and involves "human subjects" as defined by DHHS; or
Meets the FDA definition of "research" and involves "human subjects" as defined by FDA.

Is It Research?

Research as defined by DHHS regulations means "a systematic investigation, including research development, testing, and evaluation designed to develop or contribute to generalizable knowledge." [45 CFR 46.102(d)]
"Research" as defined by FDA regulations means any experiment that involves a test article and one or more human subjects, and that either must meet the requirements for prior submission to the Food and Drug Administration under section 505(i) or 520(g) of the Federal Food, Drug, and Cosmetic Act, or need not meet the requirements for prior submission to the Food and Drug Administration under these sections of the Federal Food, Drug, and Cosmetic Act, but the results of which are intended to be later submitted to, or held for inspection by, the Food and Drug Administration as part of an application for a research or marketing permit.

Currently, PNNL does not conduct FDA-regulated research. See Items for Consideration, Products Regulated by the Food and Drug Administration for additional information related to FDA-regulated human subject research and contact the IRB If you intend to conduct FDA-regulated research.

Is It Human Subject Research?

"Human subject" as defined by DHHS means a (living*) individual about whom an investigator (professional or student) conducting research obtains: 1) data through intervention or interaction with the individual, or, 2) identifiable private information. [45 CFR 46.102(f)]

"Intervention" as defined by DHHS regulations means both physical procedures by which data are collected and manipulations of the subject or the subject's environment that are performed for research purposes.
"Interaction" as defined by DHHS regulations means communication or interpersonal contact between investigator and subject.
"Private information" as defined by DHHS regulations means 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 which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public (for example, a medical record).
"Identifiable information" as defined by DHHS means information that is individually identifiable (i.e. the identity of the subject is or may readily be ascertained by the investigator or associated with the individual. This includes linking or coded information that can be traced back to an individual.

According to 21 CFR 812.3(P) FDA describes a subject as a human who participates in an investigation, either as an individual on whom or on whose specimens an investigational device is used or as a control. A subject may be in normal health or may have a medical condition or disease.

*Note: Washington State law and the federal Health Insurance Portability and Accountability Act (HIPAA) do not distinguish between living or deceased individuals so in certain instances, the Institutional Review Board (IRB) may require that deceased individuals or their families be afforded the same protection as living subjects. This may be particularly crucial when dealing with genetic or familial information when the state of the individual is unknowable or a third party may be impacted by the results of the research.

Examples of DOE Activities that Require IRB Review

The definition of "human subject research" covers a very broad range of activities including those described in 45 CFR 46. The following list provides examples of research activities that require IRB review in accordance with DOE Order and Policy 443.1 (.pdf). They represent the types of research most often conducted at PNNL.

The use of humans to examine devices, products or materials developed through research with the express purpose of investigating human-machine interfaces or evaluating environmental alterations when humans are the subjects being tested. Examples include hardware or software usability evaluation where job performance is measured or participants are videotaped; or the effects of lighting options on worker production.
Collection and use of private identifiable information, such as genetic information or medical and exposure records, even if the information was collected previously for a purpose other than the current research. Examples include employment, worker exposure, medical, or legal records.
Collection of private identifiable data, including surveys or questionnaires, through direct interaction or intervention with individuals.
Studies conducted to gain generalizable knowledge about categories or classes of subjects. Examples include oral history projects, culturally diverse populations, or linking job conditions of worker populations to hazardous or adverse health outcomes.
Traditional biomedical and clinical studies, including genetic research or analysis of private data or human specimens provided by other researchers or institutions.
Collection or use human-derived materials, such as urine, blood or blood products, skin, hair, teeth, primary or established cell lines, cultures and sub-cellular or molecular (RNA, DNA, protein) constituents, even if the materials were collected previously for a purpose other than the current research.

Note: Research funds may not be used for the creation of a human embryo or for research in which a human embryo is destroyed, discarded or knowingly subjected to risk of injury or death greater than that allowed for research on fetuses in utero under 45 CFR 46.208(a) (2) and section 498(b) of the PHS Act. The use of embryonic stem cells is limited to those listed in the NIH "Human Embryonic Stem Cell Registry" (derived before August 9, 2001) and always requires full Board review.

Additional guidance regarding the use of human biological materials, surveys and interviews, oral histories, and the use of private data or records is provided in Items for Consideration. Forms to apply for IRB review are located in the SBMS Human Subject site.

Examples of Activities That Do Not Require IRB Review

Studies to improve the safety or execution of routine procedures that apply to routine occupational activities. For example, quality assurance or assessment of off-the-shelf work place equipment or clothing where no element of research exists.
Occupational health surveillance of individual DOE employees and DOE contractor employees to determine apparent departures from typical health status and not for the purpose of obtaining generalizable knowledge.
Employee surveys or interviews used as management tools to improve worker or contractor performance as long as the identity of the participant is protected. The PNNL Quality of Life or Gallup surveys, for example.
Taking photographs, video or audio taping or focus groups, when the activities are not conducted for research purposes. For example, photographs, video or audio taped interviews conducted by PNNL public relations or other staff when the activities are not conducted for research or for the purpose of obtaining generalizable knowledge. Focus groups to assess the Laboratory's reputation within the community or discuss potential research with workers or members of a local tribal community fall into this category.
Software or hardware usability testing when conducted for standard quality assurance purposes. For instance, before delivery of a product if staff job performance will not be measured and/or their privacy or employability jeopardized by results of the testing. The use of Best Practices most always applies with some form of consent considered.

Activities Not Defined as Human Subject Research Which Require IRB Review at PNNL

Please note that the IRB may, at its discretion, choose to review a protocol that does not, under the strict interpretation of the regulations, require IRB review if it feels that additional oversight of the activities or increased protections are warranted, for instance, when PNNL staff are used as subjects.

Research using "people" or human-derived materials that does not meet the DHHS or FDA definitions of "human subject research" may be subject to IRB review at PNNL for the following reasons:

The IRB wants to be assured that: 1) sources providing human-derived materials are reputable and in good standing, 2) existing cell lines are well established and well defined with stable characteristics and 3) the materials will not be used for human in-vivo studies.
For some long-term studies, the IRB may see a need to keep the dialogue open with investigators, particularly when it appears that circumstances surrounding the research may change over time and there is potential for an increase in the level of risk to subjects that might not be detected otherwise.
When collaborating with other institutions, the IRB feels responsible to ensure that the collection of human-derived materials or private data is performed in an ethical manner and that the science PNNL is associated with is sound; regardless of the activities or the level of review required at PNNL.

Activities reviewed under these conditions will be assigned an IRB tracking number and will be subject to the same procedures and reporting requirements as those reviewed under 45 CFR 46 which are described in detail in this web site and in the SBMS Human Subject site.

Best Practices

When investigators use people in activities that do not meet the definition of human subject research, appropriate "Best Practices" should be employed to ensure the same ethical treatment is afforded the volunteers as would be expected in the conduct of actual human subjects research. For example, co-workers asked to participate in a survey or software usability testing should be told why those activities are being conducted, how the information is to be used, why they, in particular, are being invited to participate, how long it will take to complete the task, and if and how their privacy will be protected. Volunteers provided with enough information to make an "informed" decision are then free to indicate their "consent" by simply initiating the task at hand. See examples of Best Practices used by IS&E staff ( Restricted Access to content restricted access).

Making the Determination of Human Subject Research

The IRB uses the following decision chart and process to determine if activities meet the definition of human subject research.

IRB Decision Chart Page 1 IRB Decision Chart Page 2

IRB Process for Determining if an Activity is Research involving Human Subjects

Step 1:	Investigators notify the IRB of pending research by filing scope in the EPR system or by direct contact. Investigators provide the IRB PM with the statement of work and as much supporting documentation as is available or known at the time regarding the activities that potentially involve human subject research.
Step 2:	The IRB PM and/or the IRB Administrative Team use the chart above to determine if: The activity is "research" and involves "human subjects" as defined by DHHS regulations. The activity is "research" and involves "human subjects" as defined by FDA regulations. The activity does not meet the definition of human subject research but the IRB determines that review and oversight are required to meet specific internal criteria. For instance when PNNL staff is involved as subjects.* * must meet the same review and reporting requirements
Step 3:	If necessary, the IRB PM or Administrative Team meets with the investigator to make the determination.
Step 4:	The IRB PM notifies the investigator of its determination and describes the requirements for applying to the IRB for review.