By Gary Evans, Medical Writer
Trying to address “big data” threats to privacy and step out of the long shadow of human research travesties, the National Institutes of Health (NIH) recently launched its ambitious All of Us project.
The NIH is seeking 1 million Americans reflecting a broad diversity of racial and socioeconomic conditions to volunteer as research subjects. The Precision Medicine Initiative (PMI) will use whole genome sequencing and other cutting-edge tools to create, aggregate, and analyze individual health data for years into the future.
How high are the stakes? The NIH launched the initiative on May 6, 2018, in multiple cities with a marketing and messaging campaign across the social media spectrum. The NIH is trying to reach out to ethnic and racial minorities that have previously been largely left out of clinical research or directly harmed by it. As Francis Collins, MD, director of the NIH, observed in an interview, you better be ready to talk about Tuskegee if you ask an African-American to volunteer for research.
Extending the research into these communities falls in large part to Dara Richardson-Heron, MD, the chief engagement officer for the All of Us project.
“Our mission is to find 1 million or more people who reflect the rich diversity of our nation,” she said at an opening ceremony in New York City. “We’re seeking adults of all ages, races, ethnicities, sexual orientations, socioeconomic, and health statuses to join us in this unprecedented effort. We are seeking people from every corner of the U.S. because we know all too well that where a person lives has a tremendous impact to reflect on their overall health.”
Many communities have a significantly higher disease burden than others, with health disparities well-known “but not at all well understood. Research has the potential to be a powerful change agent,” she said.
The NIH is anticipating that some will view this recruitment with hesitancy, if not downright suspicion.
“There have been unspeakable instances where unethical testing and research was performed often under the guise of ‘medical treatment,’” Richardson-Heron conceded. “In other cases, whole communities have not been invited to participate in research. Our program is different. We are fully acknowledging concerns head-on because we must. We are also collaborating with our participant partners to build a program with policies and processes in place to make sure that the transgressions of the past are never, ever repeated.”
The program promises to “oversample” communities that have historically been underrepresented in medical research, which is a commendable goal, a human research legal scholar tells IRB Advisor.
The NIH “will have to overcome a long history of distrust of medical research among many minority communities,” says Carl H. Coleman, JD, a professor of law at Seton Hall University in Orange, NJ. “This distrust is likely to be exacerbated by recent revelations about misuses of personal information by Facebook and others, which could make people reluctant to share the kind of data the researchers intend to collect.”
In an opening ceremony in New York City, Collins said All of Us is among the most ambitious NIH research projects ever undertaken.
“More than almost anything we have done, this program has the potential to shed new light on how to manage disease and keep people healthy,” Collins said. “I know that is a bold statement, but I truly believe this program will be a game-changer for medical research, and ultimately for human health.”
Speaking at a similar ceremony in Detroit, Eric Dishman, director of All of Us, was no less enthusiastic.
“This is one of the most important research programs in human history — this has never been done before,” he said.
That may not be much of an exaggeration, given the level of medical technology applied to an unprecedented population that is expected to be at least half representative of diverse demographics. In a personal aside, Dishman said access to whole genome medicine essentially saved his life.
“I am alive today because I was lucky enough to be one of the early prototype patients eligible for precision medicine,” he said. “At 19, I was diagnosed with a rare form of kidney cancer and told I would be dead within nine months.”
He survived the following two decades, undergoing rounds of chemotherapy that did not find its cancerous targets.
“I was eventually running out of options and a colleague of mine helped me get access to whole genome sequencing and to get my complete electronic health record together,” Dishman said. “Armed with this new data, doctors could understand my unique form of cancer and find the treatment that was ‘for me.’”
Cancer-free, he became eligible for a kidney transplant.
“I am heathier standing before you today at age 50 than I was at 19,” he said. “That’s the power of precision medicine.”
A former Silicon Valley entrepreneur, Dishman frequently addresses the other major concern about the project: protecting the medical data volunteered by research participants.
“This is one of our biggest concerns and highest priorities to make sure that we safeguard your data and maintain positive trust with you,” he said. “If we lose that, we have the potential for losing the whole program.”
All of Us uses the PMI Privacy and Trust Principles and PMI Data Security Policy Principles and Framework, he said. The program has entered into a hacker challenge program, where computer experts probe the data set for weaknesses that could lead to a breach, he explained.
“They get what is called a ‘bounty’ — they get paid for finding holes in our systems that we can then fix,” he said.
All of Us is using commercial security systems “that constantly improve as the hackers get better,” he said. “We are holding all our partners accountable for security at the same level that we are on our systems.”
That said, the NIH program has policies to immediately alert participants regarding any security breakdown or data breach.
“There is no such thing as a 100% guarantee,” Dishman said. “If a company or an organization is promising that your data can never be hacked, then they are not being direct, transparent, and completely honest with you.”
This, again, is an uphill battle akin to the linked effort to restore trust from some communities, Coleman noted.
“The program includes strong safeguards to protect privacy and data security, but simply telling people that these safeguards exist will probably not be sufficient without larger efforts to engender greater trust in the research enterprise overall,” Coleman said.
The plan is to eventually enroll children, but currently the program is only open to adults 18 and over. Of course, there are scientific and ethical hurdles to clear to involve research on children, including the development of detailed pediatric protocols and addressing the informed consent issues.
Study participants — a term favored over “subjects” in the explanatory language of the project — will be asked to submit basic identification and medical information. Some will be asked to go to participating clinics for physical measurements and a medical workup that could include blood draws and testing needed for whole genome sequencing. According to the NIH, some of the goals of the program are:
• develop ways to measure risk for a range of diseases based on environmental exposures, genetic factors, and interactions between the two;
• identify the causes of individual differences in response to commonly used drugs;
• discover biological markers that signal increased or decreased risk of developing common diseases;
• develop new disease classifications and relationships;
• empower study participants with data and information to improve their own health;
• create a platform to enable trials of targeted therapies.
The large-scale cohort will not be focused on a single disease, but instead will be a broad resource for researchers working on all manner of inquiries.
This year marks the 15th anniversary of the international whole genome project, which spelled out the 3 billion letters in “the human DNA instruction book,” Collins said.
What if we could look at the genetics of a million people “and combine that with other information about them, their environmental exposures, diet and exercise habits, and their health histories?” he asked. “Looking at all those factors would enable us to create a priceless resource that would speed up the research needed to deliver healthcare more precisely.”
Human research on populations over time has been shown to yield medical breakthroughs, like those realized by the Framingham Heart Study in Framingham, MA, that started in 1948.
“Researchers have followed several thousand residents for decades,” Collins said. “They discovered that smoking, cholesterol, and high blood pressure are major risk factors for heat attack and stroke. Believe it or not, before that we didn’t know those things. All of Us will be 40 times larger than Framingham.”