When is human subjects research exempt from the regulatory requirements in 45 CFR 46?
The six exemptions to the regulatory requirements are described in section 46.101(b) of 45 CFR 46.
Do the exemptions extend to research that would be covered by Subparts B, C, and D?
Subpart B: YES, all exemptions may be applied to research involving pregnant women, neonates and fetuses.
Subpart C: NO, the exemptions at 46.101(b) do not apply to research involving prisoners.
Who, at my institution, is responsible for determining whether my proposed research involves human subjects but meets the criteria for one or more exemptions (46.101(b)) from regulatory requirements?
OHRP recommends that institutions adopt clear procedures under which the IRB (or some authority other than the investigator) determines whether proposed research is exempt from the human subjects regulations [see 45 CFR 46.101(b)]. Documentation should include the specific category justifying the exemption. (http://www.hhs.gov/ohrp/polciy/irbgd107.html).
Because NIH does not require IRB approval at time of application, claimed exemptions often represent the opinion of the PI, and justification provided for the exemption(s) by the Principal Investigator is evaluated during the peer review process.
What are the requirements for and the NIH interpretation of Exemption 2 (E2)?
HHS regulations state: Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior, unless:
(i) information obtained is recorded in such a manner that human subjects can be identified, directly or through identifiers linked to the subjects; and (ii) any disclosure of the human subjects' responses outside of the research could reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects' financial standing, employability, or reputation 46.101(b)(2)
NIH Interpretation: In order to be exempt from the requirement of IRB review and approval under exemption 2, researchers must propose the use of tests or procedures involving human subjects who:
cannot be identified, either directly or indirectly; OR
may be identified, but would not be put at risk if information is disclosed
What are the requirements for Exemption 4 (E4)?
HHS regulations state: Research involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if these sources are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects 46.101(b)(2).
If you receive or have access to existing individually identifiable private information or identifiable specimens from living individuals (e.g., pathology or medical records), you are conducting human subjects research. If you as the investigator or your collaborator record the information in such a manner that you cannot subsequently access or obtain direct or indirect identifiers that are linked to the subjects, research activities that involve data recorded in this manner meets the requirements of Exemption 4. If you will retain or can access any identifiers, the research project is not exempt under Exemption 4.
Is research that meets the criteria for Exemption 4 considered human subjects research?
Yes. Research that meets the criteria for Exemption 4 is Human Subjects Research.
Exemption 4 includes research involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if these sources are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects.
Please note: human subjects research that meets the criteria for Exemption 4 is not considered “clinical research” as defined by NIH; therefore, the NIH policies for addressing inclusion of women, minorities and children do not apply to research that is determined to meet the criteria for Exemption 4.
How can I determine whether my research meets the criteria for Exemption 4?
The humans subjects regulations decision charts from the Office of Human Research Protection (OHRP) will help you to see whether your research falls under the human subjects regulations and if so, whether it meets the criteria for Exemption 4.
Please note: OHRP advises that investigators should not have the authority to make an independent determination that research involving human subjects is exempt. OHRP guidance states that Exemptions should be independently determined. Institutions often designate their IRB to make this determination. Because NIH does not require IRB approval at time of application, the exemptions designated in Item 4a often represent the opinion of the Principal Investigator, and the justification(s) provided by the Principal Investigator for the exemption(s) is/are evaluated during peer review.
Does my research meet the requirements for E4 if I am using only human specimens that would have otherwise been discarded?
It depends: Specimens that would have otherwise been discarded do not automatically meet the requirements for E4. In order for the research to meet E4, such samples MUST either be BOTH existing AND publicly available or BOTH existing AND unidentifiable to all members of the research team.
My proposed studies meet the requirements for E4. What information is required about the population in the human subjects section?
Provide any and all information you have about the sample, but there is no need to obtain additional, potentially identifiable, information for the NIH population sample information requirement that is not needed for your proposed studies.
What is meant by “Coexisting” data or specimens?
Exemption 4 applies to retrospective studies of specimens and/or data that have already been collected. The materials must be “on the shelf” (or in the freezer) at the time the protocol is submitted to the IRB or other designated officials at your institution to determine whether the research is indeed exempt. Research that involves the ongoing collection of specimens and/or data does not meet the criteria for Exemption 4, even if they were destined to be discarded.
What is meant by “publicly available sources”?
This language in the regulation was intended to apply to public sources of data, such as census data. Its meaning with respect to human tissue specimens is widely debated. Although there are organizations that make human cells and tissues broadly accessible to the research community, these materials are not usually available to the public at large and are not generally considered to be publicly available.
What is meant by “identifiers linked to the subjects”?
Examples of identifiers, would include names, social security numbers, medical record numbers, pathology accession numbers, or any other “codes” that permits specimens or data to be linked to individually identifiable living individuals and perhaps also to associated medical information.
How can I tell whether my proposed research meets the Regulatory requirements for Exemption 6?
Exemption 6 (E6) states that research is exempt from the Regulatory requirements if the only involvement of human subjects is: “(6) Taste and food quality evaluation and consumer acceptance studies,
if wholesome foods without additives are consumed or
if a food is consumed 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.”
To determine whether your proposed research meets the Regulatory requirements for E6, you must determine: 1. Will participants be consuming “food”?
If the answer to this question is “no,” the proposed research does meet the regulatory requirements for E6(i).
If the answer to this question is “yes,” the proposed research does not meet the regulatory requirements for E6(i) but may meet the requirements for E6(ii); see question 3.
3. Does the food that participants will be consuming contain:
a. a “food ingredient” at or below the level and for a use found to be safe by FDA, b. an “agricultural chemical” at or below the level found to be safe by USDA, or c. an “environmental contaminant” at or below the level found to be safe by EPA?
If the answer to this question (all options) is “no,” the proposed research does not meet the regulatory requirements for E6(ii).
If the answer to this question (one or more options) is “yes,” the proposed research does meet the regulatory requirements for E6(ii).