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by Jim Gearhart

Biospecimens and The New Common Rule, Part II: Exclusions & Exemptions

This is the second in a series of three blogs about proposed changes in the Common Rule which address the ethical challenges of research on human biological samples (“biospecimens”). The attention on biospecimens is timely, as technologies have advanced dramatically how much we can learn about diseases and about ourselves from those samples. The first blog in this series looked at how a redefinition of human subject research in the Notice of Proposed Rule-Making would equate research on biospecimens with research on people. This blog will look at how that new definition shows up in some of the exclusions, exemptions, IRB review requirements, and consent form elements that the NPRM would create. A third blog will examine the NPRM’s proposed regimen for collecting, storing, and ultimately using biospecimens in future research.


Exclusions (NPRM at §__.101(b))
The NPRM introduces a new entry to Common Rule nomenclature: excluded research. The new phrase creates a category of research-like activities that could occur outside the Common Rule’s jurisdiction, but the NPRM is not allowing much biospecimen activity into that realm.

Of the eleven proposed exclusion criteria, seven mention biospecimen activities specifically. The mention usually means that biospecimens cannot be a part of the excluded research.  Even as it works to alleviate controls on some types of research, the NPRM seeks to retain almost all biospecimen research under Common Rule jurisdiction.

  • Some categories of research will be excludable unless they involve biospecimens. These are studies that the NPRM considers low-risk and already subject to other controls, ones that rely solely on surveys, educational tests, and other non-intrusive observations for their data. The NPRM would exclude these studies from Common Rule oversight as long the data they collect remained unidentifiable. But if biospecimens become involved, even as unidentifiable samples, the study would fall under Common Rule guidelines.
  • Similarly, another proposed exclusion eases existing guidelines around some research but keeps them for biospecimens. Currently, research on publicly available information is exempt from review, and in these new rules the NPRM would shift most of that research into an excluded category. Biospecimens, however, can’t go anywhere; that research still would need to qualify as exempt (see below for the difference between the two).
  • The NPRM does suggest excluding one biospecimen-related activity from oversight: research that examines what is already known about the donor’s condition. The drafters of the NPRM reason that, as long as the biospecimens are unidentifiable, researching on a known feature of the biospecimen creates few risks, and so it can be freed from Common Rule oversight.
  • The NPRM describes five additional categories that may be considered as exclusions even though they involve biospecimens. These exclusions would be agency-specific activities that the NPRM says do not add to “generalizable knowledge.” They apply to areas such as criminal justice, national security, public health, and quality assurance and would operate under other guidelines. The NPRM considers those activities outside its proposed definition of “research.”

The NPRM for the Common Rule defines research as “a systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge.” Some agency-specific activities are excluded from that definition, even though they utilize biospecimens.

Exemptions(NPRM at §__.104)
Under both the current and proposed Common Rule, certain types of research could be exempted from the Common Rule’s requirements. An exemption would represent more regulatory oversight than an exclusion because the former requires documentation of an assessment, while the latter does not.  (Currently, OHRP encourages institutions to establish policies stating who will determine eligibility for exemptions. Frequently, these determinations fall to an IRB, but the NPRM has suggested instead an online assessment tool that investigators might use.)

This NPRM largely uses degrees of risk to determine eligibility for exemption. The lower the risk to a participant, the more likely that research is to qualify as exempt, but the language of the exemption categories reflects the idea that biospecimen research usually requires more oversight rather than less. For just about any research that would include the use of biospecimens, exemption is not an option.

(Section §__.104(f) is a notable exception. This exemption category sets the NPRM’s framework for ethically collecting, storing and utilizing biospecimens in future research.  But it has some stringent requirements, and we will focus on this exemption category in an upcoming blog.)

New IRB Approval Criteria
The NPRM proposes three new criteria for an IRB to consider in a review of research. We’ll return to two of these in the upcoming blog about biospecimens and future research, but the third provision addresses an issue related to biospecimens more generally: the return of incidental findings. (NPRM at §__.111)

If an investigator intends to tell a participant about any clinically relevant findings that come from the study, the IRB must approve the investigator’s plan. The NPRM does not state whether an investigator should return results, but it does say any plan to do so would require approval.

Informed Consent (NPRM at §§__.116 and  117(b) )
The new definition of human subject research suggests a significant change in the informed consent process. If research on a biological samples is research on a person, then that person needs to consent to any research on his or her samples. The NPRM proposes to address many of the complications here through a concept of broad consent, which (again) is a topic for another blog.

But the NPRM has other suggestions for informed consent and biospecimens, too. While the NPRM endorses shorter and simpler consent forms generally, a closer focus on biospecimen-related issues could add to the consent form length and complexity.

The NPRM suggests the following new elements for any consent form that refers to biospecimen research:

  • Whenever biological samples are collected, the researcher must explain the plans for those specimens, whether a future use is anticipated or not.
  • The consent process must state whether any biospecimens will be used for profit and, if so, whether the subject would receive a share.
  • Consent forms will have to state whether and how incidental findings would be returned to a participant.
  • The consent forms also will need to state how subjects can choose to be contacted for (or excluded from) enrolling in future studies; receiving information about research results; or donating additional biospecimens.

Waivers of Informed Consent ( §__.116(e)
The NPRM adds three biospecimen-specific criteria to the existing list of criteria for waivers of consent. The effect of this is that the availability for biospecimen waivers will be narrowed significantly.

For research on identifiable specimens, waivers of informed consent are possible only if

  • The investigator can demonstrate the research could not be carried out “practicably” without identifying the specimen;
  • The scientific reasons for the research are ‘compelling’; and
  • The same research could not be conducted with specimens for which consent was received.

The limited circumstances for these waivers is consistent with the NPRM’s theme of keeping close ethical oversight on biospecimen research.

Waiver of Documentation of Informed Consent
The NPRM does not anticipate waiving any documentation of informed consent if biospecimens are involved.

In many ways the NPRM seeks to ease regulatory requirements around research. For the ethical issues around biospecimen research, however, the proposed rules tend to impose more oversight rather than less. Through those proposals, the NPRM is creating frameworks and standards specific to biospecimens, rather than grouping that research with others.

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