Changes to Common Rule could affect biobanks

ANPRM would require consent for research use of leftover clinical specimen, even if deidentified

For years, federal regulations have deemed the research use of deidentified blood and tissue samples collected in clinical procedures to be non-human subjects research, and therefore has not required informed consent from the patients from whom they were taken.

Now the U.S. Department of Health and Human Services (HHS) proposes to change that rule — a revision that could potentially affect the operations of some institutions' biobanks.

In its advance notice of proposed rulemaking (ANPRM) released in July, the department proposes requiring written consent for any research use of biospecimens collected for clinical purposes, as well as strengthened data protections to minimize the risk of re-identification. In its discussion of the proposed change, HHS notes that advances in technology put even deidentified samples at risk of being used in ways that could allow re-identification.

They also point to surveys that show people want to be able to decide whether their samples are used for research.

Jeffrey R. Botkin, MD, MPH, associate vice president for research integrity at the University of Utah in Salt Lake City, says public opinion in this area is clear.

"What we've found, what others have found, is that the majority of people are willing to have their samples used, they're willing to have their children's samples used," Botkin says. "But they want some element of choice in there. These proposed changes try to honor those desires and so are quite good and appropriate in terms of what we understand the public's request to be in this regard."

The changes as proposed would apply only to specimens collected after the effective date of the final rule. However biobanks that currently take in leftover deidentified samples from clinical procedures may be required to change the way they do business going forward.

Effects on "opt-out"

The degree of those changes would depend on the operations of an individual biobank. Vanderbilt University in Nashville, TN, for example, collects leftover blood samples from clinical use for its BioVU bank. But Todd Rice, MD, medical director of the Vanderbilt Human Research Protection Program, notes that everyone who receives care at Vanderbilt signs a form stating that they understand specimens taken from them may be used for research. People who do not want this research use of their specimens may check a box to opt out of the program.

"The (ANPRM) says that you can do a quick, short-form consent, and our BioVU patients actually do that," Rice says. "We think in the overall scheme of things, it's not going to affect us that much, although we may have to tweak that form some."

However, he says, the hospital has long collected and archived tissue samples that have been used in research.

"In some of those cases, there's no consent for the use of those — they didn't sign the BioVU form," Rice says. Depending on whether the existing samples are grandfathered in, their use in research may be curtailed.

The new regulations would affect another potential source of biobank samples — leftover blood samples from the required state screening that babies receive at birth. They are considered a potentially valuable research resource, since the samples come from all babies born in a state. However, their use without parental permission has been controversial, prompting lawsuits in two states.

At least one state — Michigan — has created a program to seek parents' consent for the use of leftover newborn blood spots. But Botkin says many other states still were considering how to handle this tricky issue.

"The proposed changes would provide a more substantive set of guidelines about what would be consistent with the regulations," Botkin says. "On the other hand, this may mean that folks will sit back to a certain extent and wait to see what happens at the federal level before they change their policy."

He says that while the change requiring explicit consent for research use of biospecimens is a good one, the proposal would require only a brief consent form generally agreeing to permit future research. In the questions section of the ANPRM there is some discussion of giving those who donate samples an opportunity to check off potential research uses that they don't want their sample used for.

"What they've proposed is a very brief consent process that's open-ended in nature," Botkin says. "And therefore it's at substantial risk, in my opinion, of becoming a perfunctory process. It's just another form to sign when you come into the hospital or clinic. You've officially gotten their written consent, but you've not really had any sort of meaningful education or engagement about the issues."

He's currently working on a program to educate parents about the research use of newborn blood spots, which could be delivered during prenatal visits. Botkin says this new requirement for consent should prompt institutions to beef up their education to patients about the benefits and risks of biobank research.

"We've found that people in the general public oftentimes have a very limited understanding of what research is all about," Botkin says. "They have a difficult time conceptualizing what the benefits and risks are of research."

A 'bond of trust'

That education process has been under way for nearly a decade at the Marshfield Clinic in Marshfield, WI, which operates an active consent biobank called the Personalized Medicine Research Project (PMRP).

Marshfield uses a community advisory board, focus groups, newsletters and other strategies to educate the community about the importance of the biobank and how samples would be used.

Jonathan C. Reeser, MD, chairman of Marshfield's IRB, says the institution's efforts helped establish a bond of trust between the clinic and the community.

"It seems to me that without that, we would not have been as successful as we were," he says. "Right now, our biobank is beyond 20,000 enrollees or samples, and to obtain that in a community of our size is pretty remarkable."

He says that he doesn't foresee any major changes in the PMRP's operation as a result of the proposed revisions to the Common Rule.

Botkin says two issues that weren't addressed in detail in the ANPRM have some potential impact on biobanks. One is the notion of group harm — whether review of a research project should consider the risks to a group from which samples are taken.

The other is return of research results to participants. Botkin notes that the revised regulations would not allow a study to be exempt from review if the researcher plans to return results to participants. What this doesn't address, he says, is the possibility that serious results could come up in the course of a study prompting a decision to seek out the participant.

"For example, if in the conduct of your research, you come across a chromosomal rearrangement or a BRCA1 mutation (indicating an increased risk of cancer), is it appropriate simply to say, 'We told people we weren't returning results, so we're not going to return those results'?" Botkin says.

"Some have argued, once you get that level of information, then you ought to feel an ethical obligation to get back to those people irrespective of what the original consent said. I think that's an interesting and important debate that still has to go on here."