Common Rule Infographic

by Jim Gearhart

The Proposed Common Rule and Biospecimens: Redefining Human Subject Research

In September the Department of Health and Human Services released a long-awaited Notice of Proposed Rule-Making (NPRM) to update the Common Rule. The Common Rule is shorthand for a set of regulations that sixteen Federal agencies share regarding the ethical treatment of people in experiments (Earlier this month Quorum provided an overview of the 519-page document). Today’s blog is the first of three that will focus on a topic that percolates throughout the new proposal: ethically managing research on biological samples. In a document with over 12,500 words, ‘biospecimen’ appears 73 times. That’s ½ of 1 percent, but it feels like more than that while you’re reading. Nearly every new guideline or section has a reference to managing biospecimens.

The changes throughout the document stem from one fundamental proposal: The NPRM suggests that we expand our definition of a human subject in research to include the study of human biological samples.

This is a significant expansion beyond the current definition. Right now, the Common Rule equates research on donated specimens with research on a human subject only when the researcher can readily identify the specimen’s donor. The proposed change discards this question of identification and establishes a new baseline assumption: research on a human biological specimen is research on a human.

The NPRM’s proposed definition of a human subject of research, with the biospecimen addition in bold (NPRM §__.102(e)(1)):

(e)(1) Human subject means a living individual about whom an investigator (whether professional or student) conducting research:

(i) Obtains data through intervention or interaction with the individual, and uses, studies, or analyzes the data;

(ii) Obtains, uses, studies, analyzes, or generates identifiable private information; or

(iii) Obtains, uses, studies, or analyzes biospecimens.


This is a key moment to consider resetting the ethical boundaries of biospecimen research. With the human genome mapped, genetic testing reveals more and more about our own bodies every day. These developments can inspire programs such as the Administration’s Precision Medicine Initiative, or personal DNA tests. The FDA has endorsed collecting genetic samples in industry-sponsored studies, and at Quorum we rarely receive a protocol that does not include some element of collecting specimens for the potential of some future use. As the biorepositories fill and the possibilities of new treatments or discoveries increase, the links between parts of ourselves that are stored somewhere and our identities also become harder to break.

As with anything in medical research, risks come along with the potential benefits. Here are a few of the issues that the modern study of biospecimen raises and which the redefinition of human subject research aims to address:

  • Privacy and security:  Researchers have demonstrated the potential to identify donors from their ostensibly anonymous specimens. One researcher identified five people through unidentified genetic information posted online. Around the same time, two research teams mapped the entire genome of Henrietta Lacks through the widely-available samples of her cells which were taken in the 1950s without her consent. What protections should donors expect when they offer their tissues or blood for research?
  • Permissions and Future Use: Researchers certainly will continue to find ways to study our specimens in ways we barely imagine now. The experience of the Havasupai Tribe, where genetic research went beyond what the tribe members had permitted, suggests an increasingly common dilemma: How do researchers request consent for unknown uses?
  • Incidental Findings: The analysis of someone’s biological material raises the potential to find a previously unknown health danger. Increasing biospecimen research increases the possibilities of such findings. What are researchers’ responsibilities to report information back, what is their ability to do so, and how will they communicate this, if at all?

These questions touch the surface of the complex issues churning around biospecimen research. As President Obama encourages us to find personal, tailored situations for our medical ailments; as private companies offer to analyze our personal genome for us and then agree to sell that information (as anonymized as it can get) to research companies; and when every blood draw at the doctor could become part of some new revelation, how should we as a society, as researchers, and as governing bodies respond?

The NPRM’s answers start with this redefinition, but from there it moves on into complex ethical territory. The expanded definition of human subject research becomes the fulcrum across which the NPRM seeks to balance the potential discoveries that biospecimens offer against the respect, justice, and protection that is due to the people who contributed those specimens. And at times, we have to balance those elements of ethical research against each other, too. Additional blogs will look more closely at the NPRM’s balancing act.


PRIM&R Human Tissue/Specimen Banking White Paper (March 2007):

NIH Proposes a data base for sharing genomic data:  79 FR 51345 (Aug. 28, 2014)

Commission for Study of Bioethics says unauthorized genome sequencing is unethical:

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