Every year, Mariko Nakano, Ph.D. (pictured above), teaches Alabama’s future doctors the terrible lessons of the Tuskegee Syphilis Study, in which federal researchers misled and withheld proper medical treatment from hundreds of African-American men, for decades, in order to observe the effects of untreated disease. The public outcry about the study led to the 1974 National Research Act, which mandated that researchers obtain informed consent from all participants in studies funded by the federal government. Now, Nakano, an ethicist and assistant professor at the UAB School of Medicine, works with bioethicists from Tuskegee University and Huntsville’s HudsonAlpha Institute for Biotechnology to set a new standard for informed consent as part of the Alabama Genomic Health Initiative (AGHI). [Learn more about the AGHI and precision medicine breakthroughs involving genetics at UAB.]
“This was our first concern, how to regain and retain trust from the people of Alabama,” says Nakano, who is part of a permanent AGHI working group along with Stephen Sodeke, Ph.D., of the National Center for Bioethics in Research and Healthcare at Tuskegee University, and Thomas May, Ph.D., senior scientist at HudsonAlpha. The group established four guiding principles for all AGHI decisions: transparency, respect, confidentiality, and fairness.
Prioritizing protections
The group, which meets monthly in person, focused first on the informed consent document that is signed by all AGHI participants. “Our goal was to explain as clearly as possible” options for participating in the study, and the protections surrounding patient data, Nakano says. Participants can choose to provide a sample but not receive results if any significant findings are discovered; receive the results themselves; share their results with their primary care provider; contribute a sample to the AGHI biobank to aid future research; or a combination of the above. The implications of each option are spelled out.
Establishing clear informed consent is crucial for all long-term studies, and particularly those in cutting-edge fields such as genetics. “Technology always advances,” Nakano says. And that means the boundary of what is possible is always shifting.
In 2012, the Presidential Commission for the Study of Bioethical Issues released a report titled “Privacy and Progress in Whole Genome Sequencing,” which made a dozen recommendations on “steps the U.S. Government can take to prevent ethical problems,” covering privacy issues, familial implications of genetic testing, and possible discrimination that could occur based on genetic results. “They proposed that researchers should de-identify the data they collect” as a central way of protecting individual rights, Nakano says. Fast-forward five years, and the research and technology have advanced to the point that a genetics expert could identify a person based on his or her genetic code alone. “Now we know that genomic data is itself personalized data,” she says. “We always have to anticipate new ethical issues.”
Information safeguards
Questions about confidentiality of data are the most common among AGHI participants, Nakano says. The ethics group trains AGHI recruiters to discuss the safeguards in place to ensure that all study data is protected and kept strictly confidential. They also offer training on the details of the relevant federal laws, such as the Health Insurance Portability and Accountability Act (HIPAA), which prohibits doctors from sharing genetic information about their patients, and the Genetic Information Nondiscrimination Act (GINA) of 2008, which protects individuals from genetic discrimination in health insurance and employment. GINA does not apply to small businesses with 14 employees or fewer, Nakano notes, and it also does not apply to life insurance, although AGHI will not return results for genes associated with Alzheimer’s disease, which some experts have worried may be used in life insurance coverage decisions. “We clearly state in the informed consent form that we will return only the results that have meaningful benefits to participants,” Nakano says. “At this time, these are the 59 actionable genes listed by the American College of Medical Genetics and Genomics.”
Based on previous studies, AGHI expects to find actionable genetic variations in 1 to 3 percent of participants. But for the other 97-99 percent of the study population, “no result” isn’t equivalent to “no problem,” Nakano says.
“An issue that comes up in any genetic testing is how to return results,” she explains. “If we say we found nothing, participants may believe that they are fine. But there are many unknown genetic-related diseases which may not be detected by genetic testing.” Making sure participants understand these facts is a key element of the duties of study coordinators, says Nakano. The AGHI’s ethics working group conducts training for all coordinators, and is available in case questions arise, she notes.
“We want to benefit the people of Alabama as much as possible,” Nakano says. “These are complicated messages, and it’s important that we deliver them as clearly as we can.” So far, a small percentage of participants have declined to allow their samples to be stored in the AGHI biobank, but most are eager to contribute to future discoveries. “They’re not just concerned about their own health, but the health of their families and descendants as well,” Nakano says.