NEW YORK — The National Institutes of Health's All of Us Research Program has started offering more than 155,000 participants access to disease risk and pharmacogenetic results based on blood samples they've shared with the program, All of Us announced Tuesday.
While the program had begun releasing genetic results for ancestry and a small number of nonclinical genetic traits in late 2020, this marks the first time All of Us is returning health-related genetic results directly to participants. The program, a landmark precision medicine research project the NIH kicked off more than four years ago, released its first set of genomic data for use by researchers earlier this year.
Returning health-related genetic results to participants was a significant undertaking, said Anastasia Wise, director of scientific return to participants and impact at All of Us. It included working with the program's institutional review board on protocols for returning results, seeking guidance from community partners to ensure information is shared in a way that's easy to understand and returned with an eye toward diversity and inclusivity, and obtaining an investigational device exemption (IDE) from the US Food and Drug Administration. All of Us received the long-awaited IDE from the FDA in 2020; at the time, All of Us officials had estimated the program would start returning health-related genetic results in late 2021.
"We really wanted to make sure that we are providing [a] responsible return to our participants," Wise said of the two years All of Us has spent developing its return protocols. Before giving back results, All of Us wanted to ensure participants would feel as if they had the support needed to understand them, she said.
In this first phase of health-related genetic results return, participants who provided a blood sample to All of Us and said they wanted to receive genomic information have the option to obtain a report on their risk of hereditary diseases — based on the analysis of 59 genes included in the American College of Medical Genetics and Genomics (ACMG)'s secondary findings list — and a pharmacogenetics report analyzing seven genes that can affect how people respond to certain medications, based on guidelines from organizations like the Clinical Pharmacogenetics Implementation Consortium and the FDA. Participants can opt to receive one of the reports, both, or neither, and results and information about All of Us can be shared with participants' healthcare providers.
All of Us is individually reaching out to the more than 155,000 participants who are eligible to receive the two reports. So far, nearly 10,000 participants have been invited to receive health-related genetic results, according to an All of Us spokesperson, and more than 56 percent of participants have responded with interest. Early participants have expressed roughly equal interest in both reports.
All of Us, in a news release, described the two reports as "actionable" but also stressed that participants shouldn't make health decisions without additional clinical testing and consultations.
The results returned to patients are research results, and positive findings should be confirmed with a clinical test, Wise said.
Part of responsibly returning health-related genetic information to participants involved setting up protocols for guiding participants to next steps after receiving a concerning test result.
Participants view results through an online portal, which also includes some basic information about genetics. All participants, regardless of their results, have the option through All of Us to schedule an appointment with a genetic counselor for free to discuss their results and next steps. Summaries of those discussions are documented and shared in the online portal, which can be sent to a participant's healthcare provider. Providers can also schedule consultations with a genetic counselor.
In some cases, participants may be required to speak with a genetic counselor to receive their results over the phone; that could be the case if results are complex or, in rare cases, if the program can't generate a result.
All of Us expects 2 to 3 percent of participants will receive a pathogenic or likely pathogenic variant result through the disease risk report. Participants who learn they're at an increased risk of a disease will have the option to undergo a clinical genetic test through Color Health — the company providing genetic counseling services for All of Us — to confirm the test results. That clinical genetic testing is free for participants.
For participants who opt to receive a pharmacogenetic report, All of Us expects almost all participants to receive at least one result that could inform prescriptions. The program advises participants not to make any changes to medications without consulting a healthcare provider and undergoing clinical testing. Participants have the option to receive clinical genetic testing through All of Us, if they would like to confirm their results.
As genetic testing has become more common, it's possible that a participant may have already received results for one of the conditions or medications tested for by All of Us, for example through a direct-to-consumer testing firm like 23andMe or through a clinical genetic testing firm like Color or Invitae.
In some cases, such results could be discordant, depending on how tests are conducted or if a test generates a false positive or false negative result.
"We can't speak to the results that a participant might have had in a different clinical or commercial application of a genetic test, but our genetic counselors can talk to participants about some of the reasons why those results might be discrepant and some of the next steps that they might want to talk to their healthcare provider about," Wise said. All of Us doesn't have an estimate for how many participants they expect to receive results that are discordant with previous tests outside of the program.
The All of Us online portal also includes information on possible benefits and risks of receiving genetic results for participants to consider before they even request a report.
"They might get information that's unexpected," Wise said. Also, participants need to know how this information could affect things like insurance coverage — while the Genetic Information Nondiscrimination Act protects individuals from discrimination in health insurance, for example, life insurance and long-term disability insurance can take genetic test results into account and may ask for them.
"We want to make sure that they're aware of all of this information before they make the decision" to receive results, she said.
All of Us began returning the first set of health-related genetic results to participants earlier this autumn, said Geoffrey Ginsburg, chief medical and scientific officer at All of Us, at a summit hosted by the Personalized Medicine Coalition last month. All of Us plans to continue rolling out access to health-related genetic results to additional participants throughout 2023, including broadening access to participants that provided saliva samples and returning reports to those who are newly enrolled in the study, according to the program.
Also, Ginsburg said at the conference that All of Us plans to initiate pediatric recruitment in early 2023; today, participants must be over the age of 18.
All of Us will also add new health-related genetic results to the disease risk and pharmacogenetic reports as evidence continues to emerge. The program doesn't currently have plans to add polygenic risk scores to the results shared with participants but will continue to consider such research and what types of results could be valuable for participants, Wise said, adding that returning information directly to participants is a core tenant of All of Us.
Participants are providing a multitude of data related to their biology, lifestyle, and environment. "In return, we really want to be very respectful of providing participants themselves this information back, based on what their own personal preferences are," Wise said. It's part of "building trust" with participants, many of whom come from populations who have historically been underrepresented in medical research, she added.
Following a beta phase of enrollment, NIH began recruiting participants for All of Us in 2018 with a goal of enrolling at least 1 million participants from diverse backgrounds to share electronic health record, health survey, and fitness tracker data, as well as biosamples for analysis. Such biomedical data is made available to researchers through a cloud-based research hub, which the NIH hopes will fuel a new generation of precision medicine studies.
So far, more than 560,000 people have consented to join All of Us, more than 394,000 of whom have completed enrollment, according to a program webpage. Nearly half of the program's participants identify with a racial or ethnic minority group, and 80 percent are from historically underrepresented populations.
Representatives from nearly a dozen national and community partners — such as the National Alliance for Hispanic Health, the American Association on Health and Disability, and PrideNET — served on a cultural awareness committee to review materials shared with participants as part of the recent return of genetic results and to ensure language was culturally appropriate and inclusive, Wise said. That has included making changes to the way the program's disease risk report breaks out population-level risks — initially, it broke down such information for males and females but has since switched to describing the category as sex assigned at birth.
All of Us is also conducting surveys with participants who receive health-related genetic results to better understand how they're using the information and whether the program is meeting their needs.
Information returned to participants needs to be "inclusive of all of the diverse populations that are part of the All of Us Research Program," Wise said.