NEW YORK (GenomeWeb) – As if enrolling 1 million participants into the Precision Medicine Initiative and keeping them engaged over many years isn't ambitious enough, the National Institutes of Health also wants to make sure that 75 percent of this cohort represents groups historically underrepresented in biomedical research.
Though the NIH is still figuring out how to define this "underrepresented" category, this is an audacious goal that if achieved, could transform the life sciences research landscape, say experts. But some doubt the NIH's ability to succeed in the current political climate.
The PMI launched by President Barack Obama aims to collect all kinds of data from participants, and allow researchers to use that information to make discoveries about what causes diseases and to advance personalized treatments. Genomic information is one type of data that the NIH wants to collect, but because not a lot of people have had genetic testing, the plan is to test participants — genotyping at first, then whole-genome sequencing once the technology is cheaper — and return results.
This is already a difficult task given the scale of the project. But in order to include significantly more individuals who haven't previously had the chance to partake in biomedical studies, recruiters have to traverse a minefield of highly sensitive, explosive issues that have kept these groups at bay — economic status, low health and science literacy, differences in priorities and values, ingrained religious and cultural beliefs, racial biases, and fear of genetic discrimination. In addition to this, the current political climate – in which government authorities are cracking down on illegal immigration and even legal immigrants from certain countries, Congress is in the process of repealing the Affordable Care Act, and the White House just issued a plan to slash the NIH budget by nearly $6 billion – could prove to be additional obstacles for the PMI.
Joon-Ho Yu, a senior fellow at the University of Washington researching culturally tailored strategies for returning genetic tests results, has been interviewing community healthcare organizations about participating in a project like PMI, and has found they are preoccupied right now with addressing patients' concerns about the Trump administration's reforms. Although staff at these organizations want to recruit participants in a PMI-type effort, he has gotten the sense in discussions with them that joining a research study may not be a priority for some of the underrepresented populations that the NIH wants to recruit.
"It's going to be tough," said Yu in an interview. However, the PMI won't advance precision medicine like it wants to without them.
It's been long known that doctors and researchers rely largely on data from studies that are conducted on white males. Though the Revitalization Act in 1993 required federally funded research studies to prioritize enrollment of women and minorities, less than 2 percent of the 10,000 cancer trials conducted with the National Cancer Institute's support included sufficient numbers of minority participants. In genetics research 90 percent of individuals used in genome-wide association studies are of European ancestry. But the status quo can't remain if the goal of biomedical research is to use genetics and other data to make treatments more personalized to the individual.
Even when some of these differences are known, researchers don't have a good understanding of how genetics works in concert with other factors like environment and lifestyle to cause disease. In wanting to overcome these disparities in biomedical research, the NIH assured early on that the PMI would be open to anyone living in America who is willing to undergo a health exam, donate a sample, and share their data. Specifically, the NIH said it would include not only racial and ethnic minorities, but more women, people of different ages, from rural areas, inner cities, in prisons, and even those with disabilities and psychiatric conditions that impair their ability to give consent for research.
Racial and ethnic minorities comprise nearly 40 percent of the US population, and genetics influences their ability to respond to drugs and risks for diseases differently than in Caucasians. For example, as many as 79 percent of Pacific Islanders and 50 percent of East Asians have genetic alterations that keep them from properly metabolizing the blood thinner Plavix, but only 2 percent of Caucasians are poor metabolizers of this drug. In the overall US population, BRCA mutations that increase the risk of breast and ovarian cancers show up in between 1 in 300 people to 1 in 500 people. But among Ashkenazi Jews, 1 in 40 people carry a BRCA mutation. In another example, although it is well known that having one or two copies of the APOE4 variant increases the risk of Alzheimer's in Caucasians in the US, this association has not been consistently replicated among African Americans, even though they tend to get Alzheimer's at similar rates as whites.
"This is the great unknown," former Intel executive Eric Dishman said at a recent NIH workshop on returning genetic test results to PMI participants. "In other words, when we're done, we're going to have data on all of us," said Dishman, who is leading NIH's program to recruit 1 million participants. Not everyone is like him, he acknowledged, "with money, speaks English, has access to CEOs and senators, and can get the resources I need to help interpret my data."
The disparities go far deeper than that. Among certain communities, research, more specifically genetic research, isn't much discussed. Within the low-socioeconomic sectors of the Latino community in the US, for example, altruistic participation in research isn't really a high priority. "Food, water, shelter … they fight for those three building blocks," said Norma Cuellar, president-elect of the National Association of Hispanic Nurses, in an interview.
There is a stigma attached to finding out they have a disease and there is limited appreciation for the fact that genetic testing can help prevent disease, she said. Some Latinos are interested in learning their genetic information, research shows, but they also have concerns about being discriminated against based on that data. If testing reveals something bad, they don't want to burden their families with this knowledge. And a religious upbringing can foster a fatalistic attitude, Cuellar said, that if they're going to die or get a disease, it's God's will.
The high percentage of undocumented Latinos in the US adds another layer of complexity to recruitment efforts. There are 55.5 million documented and 11.1 million undocumented Latinos in the US. Of the undocumented Latinos, 52 percent are Mexican, and 8 million are in the US workforce.
Although within PMI, the stated goal is to include anyone living in the US, the Trump Administration's plans to build a wall on the US-Mexico border, deport illegal aliens who have committed crimes, and beef up customs and border security, certainly won't encourage Latinos to trust a government study that asks them for biological samples, plans to analyze their DNA, and wishes to track their health and lifestyle through questionnaires. "We would already have had a difficult time in recruiting Latinos. But then to add everything that Trump has done is going to make it even more difficult," she said.
A few years ago in Flagstaff, Arizona, public health researchers conducting a childhood obesity study in a Latino neighborhood, noted "a generalized climate of fear" during and after the enactment of SB 1070 — a controversial anti-immigration law that the American Civil Liberties Union said invites racial profiling of Latinos and other minorities who look or sound "foreign." In that Flagstaff neighborhood without a major grocery store chain, where residents largely depended on fast food joints and gas station marts for their dietary needs, researchers noticed people were afraid to go out in public, let their kids run around outdoors, and there was a sharp drop in use of healthcare services.
Similarly, the PMI will not be immune to current political controversies. During the heated presidential race last summer, Vanderbilt University's Consuelo Wilkins traveled around the country hosting community engagement meetings about the PMI and found that it really resonated with some communities, particularly African Americans, that Obama was a champion for the PMI. In other places, where Obama was less popular, his involvement with the project was a reason for some to not support it.
Based on this feedback, Wilkins and her colleagues at Vanderbilt, which will organize the data coming in from volunteers within PMI, decided to deemphasize Obama's connection in their materials and focus on what the program offered. "We didn't want that to cloud their ability to give informed consent," she said.
Although these engagement meetings took place well before the Trump Administration took office, when individuals from underrepresented communities learned about the PMI, some also wondered if politics would impact its future success. "We did get questions about whether or not this program would still be supported by a new administration, whoever that might be," said Wilkins. "We also got questions specifically that if there was a Republican in office, would [PMI] still be supported."
Last year, Congress passed the 21st Century Cures Act, which contained $4.8 billion in funds to the NIH over a decade, and $1.4 billion for the PMI. But the Trump Administration's fiscal 2018 budget proposal released last week called for cutting the NIH budget by 20 percent to $25.9 billion. This creates uncertainty around future funding for the PMI as well, although Dishman has tried to reassure that the PMI is managing its budget conservatively.
The NIH must feel a lot of pressure to get the project established, "get bodies in the door," and show that this is going to work, Yu reflected. The PMI is slated to launch alpha and beta phases in the coming months and open for national enrollment in the fall. But Yu worried that a tightening of the NIH's budget could slow recruitment plans within the PMI, particularly in underrepresented communities, and limit the project's ability to return genetic test results.
During the recent NIH workshop, many genetics experts advised the institutes to return results within the PMI that guidelines bodies agree are actionable. But even then, resource poor communities may not be able to act on that information. For example, a young, African-American medical director at a community health clinic told Yu during an interview that there may be significant barriers to a Medicaid patient's ability to benefit from finding out that he's at genetic risk for Long QT syndrome, a heart condition that can cause sudden death. He doubted that the patient would be able to access a specialist and that Medicaid would probably not pay for a defibrillator if needed.
In thinking about what results to return to PMI participants, Yu advised the NIH to consider how that information would impact the most vulnerable populations first. "It's not just about getting the genomic information in hand," he said. "But these groups want to have a better sense of what benefits they might garner from this information, and they want to know what support they'll have to realize those benefits."
Participants will be able to enroll in the PMI via healthcare provider organizations or they can directly enroll through a website. The NIH and the Health Resources & Services Administration has awarded $100,000 to six community-based organizations in underserved populations, such as the San Ysidro Health Center near the US-Mexico border, to support recruitment efforts.
But healthcare providers serving these communities see patients infrequently. When they do see patients, there may be a laundry list of issues to address, and no time to discuss participating in the PMI. One consequence of this could be that providers end up enrolling relatively healthy people even within these underrepresented populations, and Yu worries this could hinder the PMI from collecting the kinds of data that would truly inform precision care in these communities.
Ultimately, what doctors, nurses, and researchers on the ground came back to over and over again is the need to foster trust within these communities. In the engagement meetings Wilkins held around the country, people were most concerned about privacy and trust. "There is, in general, a lack of trust in the government, and that was a year ago," she said. "Certainly, some of the more recent policies and decisions aren't fostering trust among vulnerable, disadvantaged, and immigrant communities."
People in these meetings asked who would have access to their data, if the government would own their data, and what the government could do with their information. For example, could the government use it to track them? Could it be used to discriminate against them or be used in legal proceedings?
When researchers approach people about participating in genetic studies, it's not uncommon for them to refuse, citing some of these same fears. And while current laws do limit who can access an individual's health data, a Republican-sponsored bill making its way through the House, H.R. 1313, has many groups worried that it would leave people more vulnerable to genetic discrimination in the workplace. If this bill passes, it could hurt recruitment in genetic research studies, like PMI, some experts have said.
Given all these considerations and challenges, Yu couldn't help but wonder if this is the right time for the PMI, and whether the project's laudable goals were feasible in the current political climate.
Cuellar, however, urged the NIH to push ahead. "I think it's the right time. If anything, this needed to be done yesterday," she said. "We need to do it because it's difficult."
Cuellar is not alone in thinking the PMI may be able to reach these communities. A positive example comes from Englewood, an economically downtrodden community in Chicago's South Side where Whole Foods opened a branch last fall.
Ahead of it's opening, there was much debate about whether locals would frequent a grocery store many think of as a high-end establishment. But that Whole Foods — part of the $20 million Englewood Square Project funded through city subsidies, a federal tax credits program launched by President Bill Clinton, and $500,000 in crowdfunding — has attempted to become a resource for the neighborhood by offering lower priced items and selling products from local vendors.
"Turns out we're so happy, because that is also near one of our clinics," said Robert Winn, associate vice chancellor for community-based practice and director of the University of Illinois Cancer Center, at the NIH workshop.
Winn is part of the Illinois-based healthcare provider consortium that will be recruiting participants within the PMI. As a result of the Whole Foods and other initiatives, he said there has been "movement around the political folks and the community folks" about participating in the project. "So, there is hope," Winn said.