Federal regulations under Title 45 CFR Part 46 apply to research involving human subjects. Research involving human subjects requires review by an Institutional Review Board. While many protocols submitted to the IRB require full-board review and/or continuing IRB oversight, some protocols the IRB receives do not involve research or human subjects. Others may constitute human subjects research but may qualify for exemption from IRB review under 45 CFR 46.101 or for expedited review under 45 CFR 46.110.
When reviewing protocols that may not involve human subjects research or may qualify for exemption from further IRB review or expedited review, IRB members must pay particular attention to the additional regulatory requirements outlined in 45 CFR 46. In order to exempt the protocol, IRB members must assess the proposed project to determine whether it fits into one of the categories for review processes other than full-board review described below and meets ethical standards for the protection of human subjects.
As noted above, federal regulations under 45 CFR 46 applies to research involving human subjects. Therefore, if a project does not involve research or include human subjects, typically, it does not require IRB oversight. While some projects clearly do not constitute research or involve human subjects, other projects are not as straightforward (e.g. quality improvement projects, program evaluation, use of coded data or specimens). Subsequently, these projects may require assessment by IRB members as to whether the project fits the definition of research and/or human subjects and ultimately requires IRB oversight.
46.102(d): Research means a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. Activities which meet this definition constitute research for purposes of this policy, whether or not they are conducted or supported under a program which is considered research for other purposes. For example, some demonstration and service programs may include research activities.
46.102(f): Human subject means a living individual about whom an investigator (whether professional or student) conducting research obtains (1) Data through intervention or interaction with the individual, or (2) Identifiable private information. Intervention includes both physical procedures by which data are gathered and manipulations of the subject or the subject's environment that are performed for research purposes. Interaction includes communication or interpersonal contact between investigator and subject. 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 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). Private information must be individually identifiable (i.e., the identity of the subject is or may readily be ascertained by the investigator or associated with the information) in order for obtaining the information to constitute research involving human subjects.
Some protocols may qualify for exemption from the federal regulations under 45 CFR 46. Although the regulations do not stipulate who makes this determination, University of Nevada, Reno policy requires that the IRB make this determination, not investigators. Aside from meeting the specific federally defined categories of exemption, the research must pose minimal risks to subjects. Under the DHHS regulations (Common Rule) minimal risk is defined as 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 [45 CFR 46.402(i)]. NOTE: The HIPAA Privacy Rule requirements still apply to exempt research.
The most common categories of exemption are:
46.101(b): Research activities in which the only involvement of human subjects will be in one or more of the following categories are exempt from 45 CFR 46:
Federally funded human subjects research involving prisoners cannot be determined to be exempt. In addition, research that may fall under exemption category 2 that involves children cannot be determined to be exempt from IRB review.
Federal regulations allow for expedited review procedures for certain kinds of research involving no more than minimal risk, and for minor changes in approved research. Expedited reviews are conducted for continuing review for certain types of protocols or protocols at certain stages (see below) and minor changes to approved research.
The relevant DHHS regulations related to expedited review follow.
46.110(a): DHHS has established a list of categories of research that may be reviewed by the IRB through an expedited review procedure. This list applies to both initial and continuing review and includes:
Protocols that require FDA oversight must also follow FDA review process requirements. The required review processes for expedited review under FDA regulations [21 CFR 56.110] are similar to those under the Common Rule. However, the definitions of research and human subjects, as well as criteria for exemption, differ from the Common Rule. Therefore, protocols that may qualify for exemption under the Common Rule, may still require FDA oversight and full-board review by the IRB. Of note, protocols that involve humanitarian use devices and which do not constitute research under FDA regulations can qualify for expedited continuing review. For further information, please refer to the Fact Sheet for IRB Members regarding FDA regulations.