NEW YORK – The US National Institutes of Health's flagship precision medicine project is looking at new ways of generating funding, such as through collaborative studies with paying partners, as it faces a shrinking budget.
The All of Us Research Program was established by the 21st Century Cures Act and launched in 2018 with a goal of enrolling 1 million participants who would share medical, genetic, and lifestyle data and fuel research to improve the understanding of disease risks and advance new precision medicine strategies. To date, it has recruited more than 834,000 participants, according to a report released last week by a program working group.
From the start, there was a focus on diversity within All of Us and an emphasis on enrolling participants who, due to their race, disability status, income, sexual orientation, or other factors, historically have been underrepresented in biomedical research. So far, 87 percent of participants are from underrepresented backgrounds, per the report. Nearly half of participants, 47 percent, are from a racial or ethnic minority group.
But the program, which is funded through Congress, this year received notably less funding than previous years, and those cuts are expected to continue.
The program received $357 million for the 2024 congressional fiscal year ending Sept. 30, representing a $184 million cut to its budget from FY2023. Further cuts are expected in FY2025 and FY2026, which will be the final year for which the Cures Act had authorized funding. The Cures Act, which passed in December 2016, stipulated a decade of funding for All of Us.
Under budgetary pressure, All of Us has had to reduce spending on enrolling new participants, said All of Us CEO Josh Denny. "Our first priority is our existing participants, data, and samples," including protecting the program's core activities like its biobank and electronic data, explained Denny, an adjunct professor in the department of biomedical informatics at Vanderbilt University Medical Center.
Within All of Us, for example, organizers had planned to begin recruiting pediatric participants in 2023. While they succeeded in enrolling the first pediatric participant before the end of the year, they soon had to stop due to budget cuts. Since then, organizers have resumed a limited recruitment effort at five sites, but they will have to halt enrollment again if the budget continues to drop in 2025, Denny said.
Congress hasn't finalized funding for FY2025. Denny said that if Congress agrees to President Joe Biden's FY2025 budget proposal, which included a request for $541 million for All of Us, the program would be able to officially move forward with pediatric enrollment and other activities. That would restore the program to funding levels seen in FY2022 and FY2023.
In the report published last week, the reflection and advancement working group, part of an All of Us advisory panel, emphasized the importance of recruiting a sufficient cohort of pediatric participants and that this could mean enrolling more than the planned 1 million participants. In fact, the working group, after reviewing the program's progress and opportunities for future expansion amid financial uncertainty, recommended that All of Us consider additional funding sources, including public-private partnerships.
"To move forward with its goal, All of Us will need to rethink its strategy and operational model to manage sustainability, be less dependent on shifting budgetary allocations, and grow with the demands of the market," the working group wrote. It noted that All of Us data could be a powerful resource for responding to national health emergencies.
Maintaining engagement
One of Denny's big concerns is that with a shrinking budget, it may become challenging to maintain engagement with participants. All of Us researchers ask participants to provide biological samples for genetic analysis and take periodic surveys about their health. In turn, participants receive certain clinically actionable genetic test results and updates about how their data is contributing to precision medicine research. Within the program, more than 144,000 participants so far have received health-related genetic test results.
The program partners with hospitals and engages with groups like the National Alliance for Hispanic Health, Asian Health Coalition, and Pyxis Partners, a social impact firm that works with organizations like the Black Greek Letter Consortium, to facilitate enrollment and establish relationships within diverse communities.
The budget cuts the program is facing in FY2025 could interfere with these engagement efforts and jeopardize researchers' ability to follow participants over time and recruit them into new studies. "It's really important, longitudinally, that we keep participants engaged," Denny said. "This is an ongoing relationship we have with participants."
The All of Us program is also piloting a series of virtual regional symposiums to solicit feedback from participants while community partners and researchers discuss the value of the program.
The working group stressed in its report that the "diversity of the All of Us cohort — unmatched by any other large cohort in existence — is its primary strength." The authors added that, for continued success, All of Us must not only keep recruiting new participants but also maintain engagement and collect additional data with existing participants.
The program should expand the amount and type of data collected on participants, including incorporating new environmental and biomarker data, and engage participants in new studies, according to the report. It is also important that participants feel "pride" in participating in All of Us and that their involvement is advancing research, the working group wrote.
Program organizers and partners should continue to meet with participants to get feedback and share updates, including having "frank discussions" about the program's finances and how priorities are set. "There should not be a rapidly growing 'ghost' cohort of participants whose level of data does not support routine use in research," the working group wrote. "Stable, predictable funding for engaging these participants regularly through ancillary studies and ongoing data collection is critical to avoid squandering this investment and infrastructure."
Amid financial pressures on the program, it's critical to keep in mind the importance of ongoing engagement with participants, agreed Russ Altman, co-chair of the reflection and advancement working group and professor of bioengineering, genetics, and biomedical data science at Stanford University. These efforts should be prioritized, and any cuts to them should be minimal, Altman said.
"One of our goals was to make it very clear that [cuts to these engagement efforts] could be a disaster and an existential threat to the project," he said of the working group's report. "If some of those groups stop participating, or the whole group loses trust, then we have a resource that doesn't have nearly the scientific value and therefore won't have the impact on health that we're hoping for."
He added that while there are other biobank projects, the All of Us program is distinctive in its decision to return information — such as certain actionable genetic test results — to participants, and this is one way the program directly benefits participants. Not all biobanks provide such information back to participants.
Toward sustainability
Given the financial uncertainty of the program's budget, the working group urged All of Us leadership to diversify its funding and become less dependent on appropriations from Congress, although this would remain its core funding stream.
All of Us could strike partnerships to conduct ancillary or collaborative studies with other organizations, including with private sector companies and consortia willing to pay to access data and recruit participants for their own trials, as well as fund additional data collection on participants. This approach will require upfront and transparent communication with participants who might be hesitant to share their data with for-profit companies and may wish to opt out.
"We think that there's messaging that you can do to anticipate these concerns," Altman said. "Not after, but before [these studies roll out], you're transparent about what the deal is, what the reasoning was for why this is a good deal, what the benefits to the resource will be, and what the costs to the resource will be."
All of Us has so far launched four such ancillary studies: Nutrition for Precision Health, Exploring the Mind, Environmental Health and Exposomics, and COVID-19 Serology. The Nutrition for Precision Health study, for example, is a five-year study funded by the NIH Common Fund. There are an additional dozen potential ancillary studies in development.
If industry partners are willing to fund new ancillary studies, that could bring in additional financial support, Denny said.
By collaborating with All of Us, researchers can save time and money by accessing biosamples and identifying participants for clinical trials more quickly, he added. The working group also suggested in the report that the data generated within All of Us could be of interest to commercial entities' drug discovery efforts.
"We're having a number of conversations now, and there's a lot of interest from a lot of different kinds of partners," Denny said, though he declined to share details on what types of collaborations could be accomplished with public-private partnerships. "In doing this, we'll always be thinking about our participants, protecting their data and our core values of the program."
Already, All of Us is at an "inflection point" in terms of the number of research projects leveraging its data, Denny said. Registered researchers can access and analyze certain All of Us data through the Researcher Workbench, a cloud-based platform. Publications citing All of Us data have increased year over year, with more than 600 papers referencing the data to date, according to the report. And as of August, there were more than 12,500 projects underway on the Researcher Workbench.
"Publications [and] use of the data are really taking off," Denny said. "We're set to capitalize on the tremendous investment that's been made so far, and really see this pay off."