Certain terms or phrases used throughout the Working Group’s response require some explanation.
Office for Human Research Protections (OHRP)
Between the time NBAC issued its report and the development of this DHHS response, the Office for Human Research Protections (OHRP) was created in the Office of Public Health and Science, as a staff office within the Office of the Secretary of Health and Human Services. OHRP has assumed the human subjects protection role previously vested in the Office for Protection from Research Risks (OPRR) at NIH. Therefore, references to OHRP in this report also refer, whenever applicable, to the former OPRR.
Definitions of types of human biological samples
NBAC classifies samples in accordance with their level of identifiability. The Working Group agrees with NBAC categories but has some reservations about the introduction of the new label “unlinked samples”. NBAC’s definition of “unlinked samples” is the same as the definition of the more commonly used term “anonymized samples.” The Working Group sees no advantage in introducing new nomenclature and suggests maintaining use of the already recognized term “anonymized samples.” Continuing to use the term “anonymized” has the advantage of permitting easy reference to current and emerging literature and educational materials on this subject. Moreover, “anonymized” is more commonly understood, self explanatory and more precise.
References to federal regulations governing human subjects protection
“Common Rule” refers to Subpart A of 45 CFR Part 46 and is broadly understood as a shorthand for federal regulations that govern the protection of human subjects in research. However, while the Common Rule applies to research conducted, supported or regulated by any federal Department or Agency that has issued regulations equivalent to Subpart A, other DHHS regulations also apply to human subjects protection. 45 CFR Part 46 Subparts B, C and D, respectively, provide additional safeguards for subjects who are pregnant women, prisoners or children. There are, in addition, significant differences between 45 CFR Part 46 and 21 CFR Parts 50 and 56 (regulations applying to FDA-regulated research only). For example, unlike the Common Rule, FDA regulations do not describe a human subject in terms of a living individual about whom data is collected through intervention or interaction or identifiable private information. Moreover, the criteria for waiver of informed consent differ substantially. FDA regulations require Institutional Review Board (IRB) review and approval of all FDA-regulated research involving human subjects. Thus, some of NBAC’s recommendations may not apply to certain research regulated by FDA.
In carrying out analysis and developing a response to NBAC’s report, the Working Group considered all applicable human subjects protection regulations. To simplify references in this report to this set of regulations, the Working Group adopted the convention of using the term “the Regulations” to refer to either or both 45 CFR Part 46 and 21 CFR Parts 50 and 56 depending upon the context of the discussion.
Research utilizing human biological materials may:
- be covered by the Regulations;
- be exempt from the Regulations;
- not involve human subjects as defined by the Regulations and therefore be not subject to the Regulations;
- or, for other reasons, be outside the jurisdiction of the Regulations.
The Working Group found that efforts to maintain these distinctions at all times were unwieldy and cumbersome. Therefore, throughout this document, the Working Group uses phrases such as “not covered by the Regulations,” “the Regulations are not applicable”or “not subject to the Regulations” to refer to any instance(s) in which the Regulations do not apply.
Finally, the Working Group notes that the phrase “exempt from IRB review 1 appears in several places in the NBAC report. Although historically it is not clear when this phrase was first introduced in discussions of IRB roles and responsibilities (it also appears in OPRR/OHRP guidance), the Working Group points out that, while the Regulations identify what is or is not exempt from the Regulations, they do not provide a mechanism to exempt a proposal from IRB review (emphasis added). Because this phrase could be misleading, the Working Group urges that, in future communications and documents, the phrase be replaced with more precise language.