As the tissue samples and DNA of more and more people are shared with researchers, the question of what information buried in those samples to give back is more pressing than ever. Now, a 335-page report from the National Academies of Sciences, Engineering, and Medicine (NASEM) released this morning urges researchers and regulators to return more biological data to the people whose samples yielded it in the first place. Giving back data to individuals is part of a broader push to offer participants a voice in research, especially research on their own tissues—but how best to do it in a way that is helpful to recipients and their physicians remains murky.
The issue has been charged for years, since expanded DNA sequencing started turning up unexpected findings in research participants’ samples that weren’t always connected to the original study—such as a gene predisposing a person to breast cancer in a project studying heart disease. In addition, scientists often uncover mutations or other findings that have questionable medical significance to an individual. A DNA quirk that might raise the risk of disease only marginally, for example, or carry uncertain medical meaning may still merit publication and help advance a field of research. For participants, this distinction can be frustrating. If their DNA is worth publishing and helps boost a scientist’s career, why can’t it also be shared with them?
Given these questions, along with inconsistent regulations, three major U.S. agencies--the Food and Drug Administration, the Centers for Medicare and Medicaid Services (CMS), and the National Institutes of Health (NIH)—turned to NASEM for help. And about a year after its work began, the NASEM authors concluded that “the expanded return of results on a cautious basis is the way to go,” says Jeffrey Botkin, a pediatrician and bioethicist at the University of Utah School of Medicine in Salt Lake City, who chaired the committee. Researchers have traditionally focused on returning results that are medically significant, meaning they have a big effect on disease risk, and are medically “actionable,” meaning something can be done to head off that disease. In 2013, the American College of Medical Genetics and Genomics in Bethesda, Maryland, put out a list of 57 gene mutations that it said fit the bill, although it later said the results should be returned only if people want them.
The NASEM authors weren’t asked to consider which gene mutations or other data should be returned—for example, the still controversial Alzheimer’s disease predisposition mutation APOE4. Instead, they weighed broader considerations, such as whether to expand the type of results and information shared, from DNA to biomarkers to potential toxins in bodily fluids. Partly based on various studies that ask research participants what they want, Botkin says various research results are “clearly of value to many participants—sometimes [for] healthcare decisions, in many circumstances for curiosity, [or] to support the relationship they develop with investigators.”
“I was markedly surprised and pleased at this report and how robust it is around acknowledging a new age of researcher–research participant partnership,” says Kathy Hudson, who recently left her post as NIH’s deputy director for science, outreach, and policy, and is now CEO of the People-Centered Research Foundation in Washington, D.C. It’s “a farewell to paternalism that I [find] really refreshing.”
A huge hurdle, however, is that the research enterprise isn’t well set up for returning many results. Doing so can be a burden for research groups, both logistically and in terms of cost. And the regulations governing return are convoluted and confusing.
The NASEM report tackles these problems in a series of 12 recommendations that urge systemic changes. Right now, research studies on human tissues are conducted in a range of labs with different quality-control measures, and there is no single accreditation process that applies across them. One big difference between labs that process tests ordered by doctors—say, for cholesterol levels—and those that process tests for research studies is that the research labs are not geared to return results to individual patients. For example, they might not be set up to keep a test result tightly matched to a particular person, the way a clinical lab, which receives special certification, must do.
Among the most sweeping recommendations in the NASEM report is that NIH help implement a certification system for research labs that process human samples, which would help govern how they are analyzed and reported; labs awarded certification can then return certain DNA findings and other information to participants who want them.
A certification process like this could help ease conflicting rules that researchers now grapple with. On one hand, CMS forbids returning results from labs that don’t have “clinical” certification, which many research labs don’t. On the other hand, participants who request their results through the Health Insurance Portability and Accountability Act of 1996, which preserves health privacy, have a right to receive them. What are research teams to do in this situation? “We know that investigators and institutions are feeling in a bind,” Botkin says.
A new certification system could help resolve that, as could the panel’s recommendation that CMS amend its rules forbidding return of results from nonclinically certified labs, to allow those certified under potential new research lab rules to give them back to participants, too. It could also make less likely some problems plaguing consumer genetic testing: Some companies claim to analyze raw data but don’t use a clinically certified lab, and the results they return can be wrong.
The NASEM report suggests other ways to ensure accuracy and transparency—something participants have often complained is missing. It urges researchers to carefully consider what will be returned before their study starts, in part based on input from potential participants, and to seek funding accordingly. Among other things, says Botkin, this is critical to keeping research participants happy—and, by extension, helping a range of studies recruit enough people to succeed.
Although the goals sound admirable, “The devil is in the details about what it means, taking into account what participants want,” says Ellen Wright Clayton, an expert in law and genetics at Vanderbilt University in Nashville. She has long worried about how returning large swaths of research results will play out for patients, doctors, and payers, and is part of a consortium called eMerge that’s studying this. Because a research volunteer told of a potential prostate cancer biomarker will turn to their doctor for help, it’s those physicians, not the researchers, who deal with the fallout, Clayton points out, even though the doctors didn’t order the tests. “It’s going to be a real challenge to return these results ethically,” she adds, in part because there just aren’t enough genetic counselors to support those receiving hard-to-interpret results. Although some will surely be helped, she says, “we can count on this being disruptive change.”