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Privacy, Informed Consent of Clinical Sequencing Top Concerns for Presidential Bioethics Commission

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By Monica Heger

The Presidential Commission for the Study of Bioethical Issues is soliciting public comment as it plans to prepare a report that will guide regulatory and policy decisions related to human whole-genome sequencing.

The commission met in San Francisco last week to discuss ethical issues associated with human sequencing. The goal of the meeting, which was webcast, was to hear from a variety of experts and stakeholders about the state of the technology, its use in research and the clinic, and the main issues associated with privacy, informed consent, and security of personal information.

The commission plans to issue policy recommendations on how to deal with these issues, but did not provide a timeline for when it plans to do so.

The topic is a tricky one because sequencing technology is advancing far more rapidly than regulatory bodies can draft guidelines on its appropriate use. Additionally, in the US, few protections exist for consumers beyond the Genetic Information Non-Discrimination Act.

These issues have not prevented a dramatic surge in human genome sequencing over the last several years, however. A significant number of individuals have already chosen to have their genomes sequenced, many for studies seeking to find the cause of a rare genetic disease or to guide treatment for cancer, and increasingly, healthy individuals are also having their genomes sequenced, either as part of research studies or because they are curious.

The nonprofit Rare Genomics Institute was recently launched to help link children with rare, undiagnosed diseases to academic institutions doing whole-genome or whole-exome sequencing. And other institutions, such as the University of Michigan and the British Columbia Cancer Agency, have launched clinical cancer sequencing pipelines. Many argue that in these cases, the potential benefits of sequencing outweigh any potential harms related to privacy or informed consent. In some cases, however, the protocols require sequencing of healthy family members, and it is unknown how that information might impact things like health insurance or employment.

"There's a range of concerns," said commission chair Amy Gutmann, president of the University of Pennsylvania. "We have to tackle them and come up with a clear, nuanced view about how to accommodate concerns for privacy and anonymity at the same time as supporting the progress of the kind of science that holds out great hope, enormous potential, and some real benefits for individuals and society," she said.

Benefits Outweigh the Risks

Retta Beery, the mother of twins who had their genomes sequenced last year in order to yield a molecular diagnosis and treatment for a rare movement disorder, spoke in front of the commission on her experience with the technology (CSN 6/14/2011). Acknowledging that her situation is not typical — her husband, Joe Beery, is Life Technologies' chief information officer — she essentially said that whole-genome sequencing saved her twins' lives, and that it had the potential to help other "patients without a diagnosis or with a misdiagnosis."

She noted that the risk of her twins' genetic information not being private was the least of her concerns, given that their disease was so severe that she wasn't sure how long her daughter, in particular, would live.

"The matter of privacy versus a life-saving treatment didn't have equal balance at all," Beery said.

Sequencing revealed that the twins had two rare mutations — one inherited from their mother, the other from their father — that was causing their disorder.

Additionally, as part of the study, Beery, her husband, and their unaffected oldest son had candidate regions of their genomes sequenced, which confirmed that their son did not inherit the mutations.

This was important, said Beery, because "for this particular disorder, the onset can come at any time."

Additionally, she said that the sequencing has so far not had any impact on the family's medical insurance coverage.

Beery added that she has spoken to numerous other families of children with rare diseases and estimated that only one out of every 100 or so is concerned about sharing their genetic data when it means helping their own children and potentially helping others.

"There are a lot of patients looking for answers," she said. Those that are sharing their information "are doing this for the purposes of discovery and potentially helping others and their own children," she said.

Other parents of children with rare disease that are turning to whole-genome sequencing have expressed similar sentiments. For instance, Jeneva Stone, whose son has a rare disorder and whose exome will be sequenced through the Rare Genomics Institute, has said that given that his condition is very visible and not something that could have been hidden from health insurance companies anyways, she is not concerned about privacy.

However, as part of the project, her own exome will be sequenced, and while she said the risks still outweighed the potential benefits of finding a diagnosis for her son, it was unclear whether she would have to disclose information about her genome to insurance companies, and whether — if the sequencing returned disease risk variants — that would qualify as a pre-existing condition (CSN 1/25/2012).

Unequal Access to Healthcare

It is precisely these uncertainties about how genomic information will be used that have some researchers worried about the rapid advance of sequencing into the clinic.

"Right now, it's easier to get screwed because of your genome than cured," said John Wilbanks, a senior fellow at the Kauffman Foundation and a founder of the project Consent to Research. "There's a gulf right now between the clinical efficacy and the ability to be hurt," he said.

For example, if sequence data uncovers an elevated risk for prostate cancer, medically, there's very little that can be done about that, he said. But health insurance companies can still raise their rates. Nevertheless, "some are making the gamble that a cure will come and it's worth the higher insurance rates," he said.

Currently, many of the healthy people who have had their genomes sequenced and made that knowledge public have been so-called "high status" people, said Pilar Ossorio, an associate professor of law and bioethics at the University of Wisconsin Law School. For those, making genomic information public carries less risk because they have the reputation and financial means, so it is less likely that they will be dropped from their insurance companies or have their rates dramatically raised.

But someone without those means or status is more likely to be taken advantage of, she said. Age also plays a role. For instance, if disease risk variants are discovered in the genome of an older person, "those risks will either have materialized or they won't." For example, Steven Pinker recently revealed some of his genetic information, including a variant that increases his risk for going bald. However, the Harvard psychologist is "probably not going to go bald tomorrow even though his genome suggests he could," Ossorio said.

By contrast, a 25-year-old that has his genome sequenced might be at a greater risk of being harmed by the information because it is still unknown which variants will materialize and which will not.

Given that healthcare is not a universal right in the United States, the availability of genomic data offers countless opportunities to deny access, she added.

Every year, around 25 million individuals are required to sign authorizations for the release of health records for things like employment, insurance, and workers compensation benefits, said Mark Rothstein, the Herbert F. Boehl Chair of Law and Medicine at the University of Louisville School of Medicine.

If sequence data becomes integrated into health records, third parties would have countless opportunities to use that information, potentially to the detriment of the patient, he said.

"If you test it, or sequence it, the results will be used," he said. "The only questions are how broadly, for what purposes, and with what consequences."

For instance, he said, if someone is making plans for long-term care as he or she ages, will providers or insurance companies be able to require that the person take a test for Alzheimer's risk variants? Or, given that the person has already had his genome sequenced, will he have to provide that information and will providers be able to charge a higher rate?

Informed Consent

Trying to parse the potential consequences of genomic sequence data is tricky enough, but figuring out a clear and informative way to communicate the potential risks and benefits to patients or research subjects participating in sequencing experiments adds another layer of complexity to the commission's task.

Currently, each institution has its own protocol for informed consent, and its own way of keeping genomic information anonymous or in some cases giving the subjects access to so-called clinically actionable information.

Daniel Masys, an affiliate professor of biomedical and health informatics at the University of Washington School of Medicine, said that when he was previously at Vanderbilt University, he helped start a project to integrate genotyping of pharmacogenomic genes with patients' electronic medical records.

The informed consent was an opt-out, rather than an opt-in, he said. He said the team chose this strategy because it was found that in an opt-in scenario much fewer patients would choose to have those genes interrogated and stored in their records. However, when the patients were surveyed, only about 5 percent of them were averse to the idea of the experiment, which is the same number of patients that choose to opt out, he said.

Many of the commission members questioned whether that type of protocol would work for something like whole-genome sequencing.

The opt-out system "concerns me," said Nita Farahany, a commission member and associate professor of law and philosophy at Vanderbilt University Law School. "We will struggle with issues of privacy," she said, adding that the data could impact more than just the specific patient, but also family members.

Masys acknowledged that consent in a whole-genome sequencing study for discovery purposes is completely different from consenting to have a handful of pharmacogenomic genes genotyped. For anyone participating in a whole-genome sequencing study, unexpected variants will be uncovered, he said. Consent forms should appropriately convey this risk.

Additionally, commission members questioned the idea of whole-genome sequencing of newborns, with particular questions about what would happen to the data when the child came of age. Until now, the genetic counseling community has argued that children should not be tested for diseases that do not manifest in adulthood, said Wilbanks. "But those that are advocating newborn whole-genome sequencing are just throwing that out in one swoop," he said.

Policies will have to be put into place that decide, if newborns are to be sequenced, how that data should then be used, what information the parents would have the right to know, and how that would change as the child grew to adulthood, he said.

The commission plans to use the comments gathered in the meeting to write a report with policy recommendations on how to deal with issues like privacy, informed consent, and the potential consequences of genomic information being accessible.

Currently, "people enjoy both the advantages of being treated in a manner independent of the genome, and the consequences," said Jim Wagner, the commission's vice-chair and president of Emory University. But the advent of "genomic literacy has the potential of changing that … and that's where the ethical considerations lie," he said.


Have topics you'd like to see covered by Clinical Sequencing News? Contact the editor at mheger [at] genomeweb [.] com.

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