Precision Medicine concept
Is the value of "personalized medicine" over-promised? Why is the quality of health care declining for many people despite the pace of innovation? Do patients and doctors have conflicting priorities? What is the best path forward?
"How do we generate evidence for value, which is what everyone is asking for?"
Some of the country's leading medical experts recently debated these questions at the prestigious annual Personalized Medicine Conference, held at Harvard Medical School in Boston, and LeapsMag was there to bring you the inside scoop.
Personalized Medicine: Is It Living Up to the Hype?
The buzzworthy phrase "personalized medicine" has been touted for years as the way of the future—customizing care to patients based on their predicted responses to treatments given their individual genetic profiles or other analyses. Since the initial sequencing of the human genome around fifteen years ago, the field of genomics has exploded as the costs have dramatically come down – from $2.7 billion to $1000 or less today. Given cheap access to such crucial information, the medical field has been eager to embrace an ultramodern world in which preventing illnesses is status quo, and treatments can be tailored for maximum effectiveness. But whether that world has finally arrived remains debatable.
"I've been portrayed as an advocate for genomics, because I'm excited about it," said Robert C. Green, Director of the Genomes2People Research Program at Harvard Medical School, the Broad Institute, and Brigham and Women's Hospital. He qualified his advocacy by saying that he tries to remain 'equipoised' or balanced in his opinions about the future of personalized medicine, and expressed skepticism about some aspects of its rapid commercialization.
"I have strong feelings about some of the [precision medicine] products that are rushing out to market in both the physician-mediated space and the consumer space," Green said, and challenged the value and sustainability of these products, such as their clinical utility and ability to help produce favorable health outcomes. He asked what most patients and providers want to know, which is, "What are the medical, behavioral, and economic outcomes? How do we generate evidence for value, which is what everyone is asking for?" He later questioned whether the use of 'sexy' and expensive diagnostic technologies is necessarily better than doing things the old-fashioned way. For instance, it is much easier and cheaper to ask a patient directly about their family history of disease, instead of spending thousands of dollars to obtain the same information with pricey diagnostic tests.
"Our mantra is to try to do data-driven health...to catch disease when it occurs early."
Michael Snyder, Professor & Chair of the Department of Genetics and Director of the Center for Genomics and Personalized Medicine at Stanford University, called himself more of an 'enthusiast' about precision medicine products like wearable devices that can digitally track vital signs, including heart rate and blood oxygen levels. "I'm certainly not equipoised," he said, adding, "Our mantra is to try to do data-driven health. We are using this to try to understand health and catch disease when it occurs early."
Snyder then shared his personal account about how his own wearable device alerted him to seek treatment while he was traveling in Norway. "My blood oxygen was low and my heart rate was high, so that told me something was up," he shared. After seeing a doctor, he discovered he was suffering from Lyme disease. He then shared other similar success stories about some of the patients in his department. Using wearable health sensors, he said, could significantly reduce health care costs: "$245 billion is spent every year on diabetes, and if we reduce that by ten percent we just saved $24 billion."
From left, Robert Green, Michael Snyder, Sandro Galea, and Thomas Miller.
(Courtesy Rachele Hendricks-Sturrup)
A Core Reality: Unresolved Societal Issues
Sandro Galea, Dean and Professor at Boston University's School of Public Health, coined himself as a 'skeptic' but also an 'enormous fan' of new technologies. He said, "I want to make sure that you all [the audience] have the best possible treatment for me when I get sick," but added, "In our rush and enthusiasm to embrace personalized and precision medicine approaches, we have done that at the peril of forgetting a lot of core realities."
"There's no one to pay for health care but all of us."
Galea stressed the need to first address certain difficult societal issues because failing to do so will deter precision medicine cures in the future. "Unless we pay attention to domestic violence, housing, racism, poor access to care, and poverty… we are all going to lose," he said. Then he quoted recent statistics about the country's growing gap in both health and wealth, which could potentially erode patient and provider interest in personalized medicine.
Thomas Miller, the founder and partner of a venture capital firm dedicated to advancing precision medicine, agreed with Galea and said that "there's no one to pay for health care but all of us." He recalled witnessing 'abuse' of diagnostic technologies that he had previously invested in. "They were often used as mechanisms to provide unnecessary care rather than appropriate care," he said. "The trend over my 30-year professional career has been that of sensitivity over specificity."
In other words: doctors rely too heavily on diagnostic tools that are sensitive enough to detect signs of a disease, but not accurate enough to confirm the presence of a specific disease. "You will always find that you're sick from something," Miller said. He lamented the counter-productivity and waste brought on by such 'abuse' and added, "That's money that could be used to address some of the problems that you [Galea] just talked about."
Do Patients and Providers Have Conflicting Priorities?
Distrust in the modern health care system is not new in the United States. That fact that medical errors were the third leading cause of death in 2016 may have fueled this mistrust even more. And the level of mistrust appears correlated with race; a recent survey of 118 adults between 18 to 75 years old showed that black respondents were less likely to trust their doctors than the non-Hispanic white respondents. The black respondents were also more concerned about personal privacy and potentially harmful hospital experimentation.
"The vast majority of physicians in this country are incentivized to keep you sick."
As if this context weren't troubling enough, some of the panelists suggested that health care providers and patients have misaligned goals, which may be financially driven.
For instance, Galea stated that health care is currently 'curative' even though that money is better spent on prevention versus cures. "The vast majority of physicians in this country are incentivized to keep you sick," he declared. "They are paid by sick patient visits. Hospital CEOs are paid by the number of sick people they have in their beds." He highlighted this issue as a national priority and mentioned some case studies showing that the behaviors of hospital CEOs quickly change when payment is based on the number of patients in beds versus the number of patients being kept out of the beds. Green lauded Galea's comment as "good sense."
Green also cautioned the audience about potential financial conflicts of interest held by proponents of precision medicine technologies. "Many of the people who are promoting genomics and personalized medicine are people who have financial interests in that arena," he warned. He emphasized that those who are perhaps curbing the over-enthusiasm do not have financial interests at stake.
What is the Best Path Forward for Personalized Medicine?
As useful as personalized medicine may be for selecting the best course of treatment, there is also the flip side: It can allow doctors to predict who will not respond well—and this painful reality must be acknowledged.
Miller argued, "We have a duty to call out therapies that won't work, that will not heal, that need to be avoided, and that will ultimately lead to you saying to a patient, 'There is nothing for you that will work.'"
Although that may sound harsh, it captures the essence of this emerging paradigm, which is to maximize health by using tailored methods that are based on comparative effectiveness, evidence of outcomes, and patient preferences. After all, as Miller pointed out, it wouldn't do much good to prescribe someone a regimen with little reason to think it might help.
For the hype around personalized medicine to be fully realized, Green concluded, "We have to prove to people that [the value of it] is true."
(Left to right) Vickie Naylor, Bernadine Clay, and Donna Maxey read a memory prompt as they take part in the Sharing History through Active Reminiscence and Photo-Imagery (SHARP) study, September 20, 2017.
In 2020, a first-of-its kind study in JAMA linked Alzheimer’s incidence to “neighborhood disadvantage,” which is based on SDOH indicators. Through autopsies, researchers analyzed brain tissue markers related to Alzheimer’s and found an association with these indicators. In 2022, Ryan Powell, the lead author of that study, published further findings that neighborhood disadvantage was connected with having more neurofibrillary tangles and amyloid plaques, the main pathological features of Alzheimer's disease.
As of yet, little is known about the biological processes behind this, says Powell, director of data science at the Center for Health Disparities Research at the University of Wisconsin School of Medicine and Public Health. “We know the association but not the direct causal pathway.”
The corroborative findings keep coming. In a Nature study published a few months after Powell’s study, every social determinant investigated affected Alzheimer’s risk except for marital status. The links were highest for income, education, and occupational status.
Clinical trials on new Alzheimer’s medications get all the headlines but preventing dementia through policy and public health interventions should not be underestimated.
The potential for prevention is significant. One in three older adults dies with Alzheimer's or another dementia—more than breast and prostate cancers combined. Further, a 2020 report from the Lancet Commission determined that about 40 percent of dementia cases could theoretically be prevented or delayed by managing the risk factors that people can modify.
Take inactivity. Older adults who took 9,800 steps daily were half as likely to develop dementia over the next 7 years, in a 2022 JAMA study. Hearing loss, another risk factor that can be managed, accounts for about 9 percent of dementia cases.
Clinical trials on new Alzheimer’s medications get all the headlines but preventing dementia through policy and public health interventions should not be underestimated. Simply slowing the course of Alzheimer’s or delaying its onset by five years would cut the incidence in half, according to the Global Council on Brain Health.
Minorities Hit the Hardest
The World Health Organization defines SDOH as “conditions in which people are born, work, live, and age, and the wider set of forces and systems shaping the conditions of daily life.”
Anyone who exists on processed food, smokes cigarettes, or skimps on sleep has heightened risks for dementia. But minority groups get hit harder. Older Black Americans are twice as likely to have Alzheimer’s or another form of dementia as white Americans; older Hispanics are about one and a half times more likely.
This is due in part to higher rates of diabetes, obesity, and high blood pressure within these communities. These diseases are linked to Alzheimer’s, and SDOH factors multiply the risks. Blacks and Hispanics earn less income on average than white people. This means they are more likely to live in neighborhoods with limited access to healthy food, medical care, and good schools, and suffer greater exposure to noise (which impairs hearing) and air pollution—additional risk factors for dementia.
Related Reading: The Toxic Effects of Noise and What We're Not Doing About it
Plus, when Black people are diagnosed with dementia, their cognitive impairment and neuropsychiatric symptom are more advanced than in white patients. Why? Some African-Americans delay seeing a doctor because of perceived discrimination and a sense they will not be heard, says Carl V. Hill, chief diversity, equity, and inclusion officer at the Alzheimer’s Association.
Misinformation about dementia is another issue in Black communities. The thinking is that Alzheimer’s is genetic or age-related, not realizing that diet and physical activity can improve brain health, Hill says.
African Americans are severely underrepresented in clinical trials for Alzheimer’s, too. So, researchers miss the opportunity to learn more about health disparities. “It’s a bioethical issue,” Hill says. “The people most likely to have Alzheimer’s aren’t included in the trials.”
The Cure: Systemic Change
People think of lifestyle as a choice but there are limitations, says Muniza Anum Majoka, a geriatric psychiatrist and assistant professor of psychiatry at Yale University, who published an overview of SDOH factors that impact dementia. “For a lot of people, those choices [to improve brain health] are not available,” she says. If you don’t live in a safe neighborhood, for example, walking for exercise is not an option.
Hill wants to see the focus of prevention shift from individual behavior change to ensuring everyone has access to the same resources. Advice about healthy eating only goes so far if someone lives in a food desert. Systemic change also means increasing the number of minority physicians and recruiting minorities in clinical drug trials so studies will be relevant to these communities, Hill says.
Based on SDOH impact research, raising education levels has the most potential to prevent dementia. One theory is that highly educated people have a greater brain reserve that enables them to tolerate pathological changes in the brain, thus delaying dementia, says Majoka. Being curious, learning new things and problem-solving also contribute to brain health, she adds. Plus, having more education may be associated with higher socioeconomic status, more access to accurate information and healthier lifestyle choices.
New Strategies
The chasm between what researchers know about brain health and how the knowledge is being applied is huge. “There’s an explosion of interest in this area. We’re just in the first steps,” says Powell. One day, he predicts that physicians will manage Alzheimer’s through precision medicine customized to the patient’s specific risk factors and needs.
Raina Croff, assistant professor of neurology at Oregon Health & Science University School of Medicine, created the SHARP (Sharing History through Active Reminiscence and Photo-imagery) walking program to forestall memory loss in African Americans with mild cognitive impairment or early dementia.
Participants and their caregivers walk in historically black neighborhoods three times a week over six months. A smart tablet provides information about “Memory Markers” they pass, such as the route of a civil rights march. People celebrate their community and culture while “brain health is running in the background,” Croff says.
Photos and memory prompts engage participants in the SHARP program.
OHSU/Kristyna Wentz-Graff
The project began in 2015 as a pilot study in Croff’s hometown of Portland, Ore., expanded to Seattle, and will soon start in Oakland, Calif. “Walking is good for slowing [brain] decline,” she says. A post-study assessment of 40 participants in 2017 showed that half had higher cognitive scores after the program; 78 percent had lower blood pressure; and 44 percent lost weight. Those with mild cognitive impairment showed the most gains. The walkers also reported improved mood and energy along with increased involvement in other activities.
It’s never too late to reap the benefits of working your brain and being socially engaged, Majoka says.
In Milwaukee, the Wisconsin Alzheimer’s Institute launched the The Amazing Grace Chorus® to stave off cognitive decline in seniors. People in early stages of Alzheimer’s practice and perform six concerts each year. The activity provides opportunities for social engagement, mental stimulation, and a support network. Among the benefits, 55 percent reported better communication at home and nearly half of participants said they got involved with more activities after participating in the chorus.
Private companies are offering intervention services to healthcare providers and insurers to manage SDOH, too. One such service, MyHello, makes calls to at-risk people to assess their needs—be it food, transportation or simply a friendly voice. Having a social support network is critical for seniors, says Majoka, noting there was a steep decline in cognitive function among isolated elders during Covid lockdowns.
About 1 in 9 Americans age 65 or older live with Alzheimer’s today. With a surge in people with the disease predicted, public health professionals have to think more broadly about resource targets and effective intervention points, Powell says.
Beyond breakthrough pills, that is. Like Dorothy in Kansas discovering happiness was always in her own backyard, we are beginning to learn that preventing Alzheimer’s is in our reach if only we recognized it.