Scientists Raise Concerns About Revisions to Human Research Regulations

The revisions, enacted last month, are an attempt to strike a better balance between patients’ need for privacy and the benefits of using their tissue for research. In a paper published January 31 in JAMA Oncology, a group of clinicians and ethicists from the University of Michigan and the University of Pennsylvania argue that the revisions could have unintended consequences for research with various types of biospecimens, and propose that regulators should consider them differently when creating research protections.

“Not all specimens are equal,” says coauthor Kayte Spector-Bagdady, a professor at the University of Michigan’s Center for Bioethics and Social Sciences in Medicine who chairs the center’s research ethics committee. For instance, cell lines are often taken from cancer patients who undergo invasive surgery to remove aggressive tumors. Because the samples have to be preserved and cultured as soon after their extraction as possible, this gives little room to obtain informed consent, as people tend to be more distracted by the risks of the surgery than any risks of research. “The irony is that the tumors that make the best cell lines . . . are the kinds of tumors that kill people the fastest. [These] people are likely not to be alive for very long to keep going back to ask them for their permission for different kinds of research.”

The Common Rule makes no special provision for situations like these, creating the possibility that the development and use of cell lines could be impeded down the line if requirements for informed consent should change. And according to the new revisions, they might very well change.

We’ve got all kinds of laws about whether there’s a privacy interest in things that you’ve abandoned, [but] there’s so little law in ownership of cell lines and ownership of tissue.

—Paul Lombardo, Georgia State University College of Law

Currently, informed consent is only required for specimens that are considered “identifiable,” that is, if they are accompanied with personal data such as the donor’s name. But which specimens should be considered identifiable—in an age where technological advances have made it possible to identify someone’s tissue through genetic sequencing—is a question that regulators haven’t clearly addressed. With the new revisions, they’ve left that up to an advisory committee to decide on every few years. This could have unprecedented consequences for cell line research, the authors argue.  

If all biospecimens were eventually be considered identifiable, that would mean that contributors can theoretically choose to withdraw their specimen at any time, explains Spector-Bagdady. “But if researchers invested tens of thousands of dollars and years—if not decades—of their life to developing certain cell lines, what you take away from a researcher is so much greater,” she says. “So when the committee is reconsidering the identifiability of these specimens, they should take that balance between value to science and privacy a little bit differently.”

Spector-Bagdady and her colleagues think that if the advisory committee does decide to consider all biospecimens as identifiable, it should not allow people to withdraw their cells from research if they’ve been grown into cell lines, for instance.

Another area where cell lines should be treated differently than other biospecimens is from a property point of view, the researchers argue. Whether people have property rights to the biospecimens they contribute isn’t a question that is addressed by Common Rule regulations—the revisions only include a requirement that researchers have to disclose whether they might commercialize someone’s specimens in the future. “We’ve got all kinds of laws about whether there’s a privacy interest in things that you’ve abandoned,” remarks Paul Lombardo, a bioethics and law professor at Georgia State University College of Law, but “there’s so little law in ownership of cell lines and ownership of tissue.”

However, this is an issue that the public has become increasingly concerned with in recent years, he explains, especially since the publication of Rebecca Skloot’s book about Henrietta Lacks, and other cases such as John Moore, a leukemia patient who donated blood samples in the 1970s in the belief it was going to be used for diagnostic purposes, when in fact the material was cultured into a cell line that became part of a patent application. This escalated to a court case in 1990, when the California Supreme Court decided that a patient’s discarded tissue doesn’t qualify as his own personal property. “The public [became] aware that, wow, if you go in and give blood to somebody, they might do something with it, make a billion dollars, and you don’t get any of it,” Lombardo says.

Spector-Bagdady and her colleagues argue that because researchers invest a lot of time and effort into creating and maintaining cell lines, they warrant special considerations with regard to property interests. The authors liken the development of a cell line to the creation of a statue out of an abandoned piece of marble: although the material stems from the person who discarded it, the sculptor has put in a lot of time and effort that give the marble statue the high value that it eventually has.

During the revisions to the Common Rule, regulators—officials from 16 federal agencies, including the Department of Health and Human Services—debated whether to implement a controversial proposal that would consider all biospecimens inherently identifiable, and thereby require informed consent for all of them. This was intended to prevent a Henrietta Lacks–type situation from occurring again. But the proposal was met with a lot of pushback, opponents arguing it would create unnecessary red tape, be expensive to implement, and ultimately slow down scientific research.

So instead of redefining what identifiability means, regulators decided to create an advisory committee of scientific and data science experts who will reconsider the concept on a regular basis—or “[kick] the can down the road,” according to Spector-Bagdady. “Identifiability is not a binary concept,” she says. “Whether something is de-identified ‘enough’ isn’t a [scientific] question, it’s a risk question: How much risk that a specimen can be de-identified are we willing to accept to be able to do this research?”

For that question to be adequately assessed, she and her colleagues suggest that ethicists and health policy experts should be able to weigh in on that advisory committee.

Melissa Goldstein, a bioethics, law, and policy professor at George Washington University’s Milken Institute School of Public Health, also considers the status quo to be an outdated concept of identifiability. She was involved in discussions in revising the Common Rule as an assistant director of Bioethics and Privacy in the White House Office of Science and Technology during the final year of President Barack Obama’s administration.

Goldstein suggests that privacy concerns in biospecimen research should be addressed as they are in other fields, where governments or corporations such as Facebook or airlines collect vast amounts of personal data: they are legally required to conduct a risk assessment in which they estimate the probability of a data breach occurring, and set security measures in place that reflect that risk. “If you assume that these biospecimens or cell lines are identifiable, then you have to account for that,” she says, for instance, by protecting specimens through encryption and two-factor authentication in the same way as one would protect personal data. Risk assessments should be undertaken for all biospecimens and personal data used in research—not only certain tissue types, she adds.

Goldstein’s main concern is that if regulators don’t address property, dignity, and privacy concerns sufficiently, it may ultimately come at a cost to science. “I see it as a real risk that if we don’t treat those people right and the information that they give to us, they’re not going to buy into the enterprise,” and be discouraged from contributing tissue. “I think that is the biggest risk to us being able to conduct research in an appropriate manner.”

Correction (February 19): We have updated the article to note that one of the authors is from the University of Pennsylvania and to correct a quote in the 13th paragraph from Spector-Bagdady in which she misspoke. The Scientist regrets the errors.