Big Ideas: Precision Medicine: Balancing the Promise and Pitfalls

From the president to your next door neighbor, people are increasingly aware of and excited about genetic medicine. But how should hospitals get involved?

This article first appeared in the December 2016 issue of HealthLeaders magazine.

Whether you call it precision medicine, personalized medicine, genetic medicine, or by a term yet to be coined, decoding DNA has begun to revolutionize the practice of medicine. In many instances, the science exists to quantify an individual's predisposition for a specific disease or target a precise mutation within a tumor's own genes.

The promise of such advances is so powerful that President Barak Obama earmarked $215 million of the country's 2016 budget to the Precision Medicine Initiative, intended to accelerate the development of new genetically based tests, tools, and treatments.

And the majority of U.S. adults are interested in being part of these discoveries, according to a study funded by the Foundation for National Institutes of Health. The study, published by PLOS ONE, revealed 79% of those surveyed support the idea of a national cohort study, while 54% would definitely or probably participate if asked.

What individuals crave even more, it seems, is insight into their own genetic profile, which can be bought for as little as $199 and some spit. The cost of full genome sequencing is now around $2,000, a modest expense compared to the $100 million it cost in the not-too-distant past.

Expanse of the unknown
But for all of the enticing questions genetic research can currently answer, it raises exponentially more.

When it comes to any genetic test, the healthcare community has before it two key questions, according to Lawrence Brody, PhD, director of the division of genomics and society at the National Human Genome Research Institute (NHGRI): "Do they enhance outcomes and do they make healthcare essentially more effective?"

"I think that's the bar most of us in our institute would like to be able to test," he says. "We're at a very intense phase of research where we're trying to figure out what we can learn in regard to treating patients and potentially in regard to preventing them from being patients in the first place."

Among genetic experts, there are two schools of thought surrounding the extent a person's DNA should be explored, says Brody. In the minority are proponents of sequencing a person's entire genome at a certain time, such as birth or age 18, and having that information available in a person's electronic medical record to be consulted as necessary throughout his or her life.

"We're not jumping on it yet because the technology for sequencing the genome keeps changing and there is definitely some worry that you would want to just sequence it again and again," he says. Another quandary raised by such broad testing is the multitude of genetic "variants of unknown significance."

In other words, while scientists have the ability to sequence the entire genome, they don't yet have the knowledge to evaluate it.

For those reasons, a more traditional point of view is that specific genes should be tested to answer specific questions. But even with that approach, it's possible to end up with answers to questions you didn't ask, also referred to as accidental or incidental findings.

"Often I'm pleasantly surprised that patients are smarter than their doctors and they recognize that they could be at genetic risk for disease A or disease B and they refer themselves."

For example, a person undergoes exome sequencing to understand an abnormal lipid profile, and incidentally learns about increased risk for an unrelated disease. "Now you've got a different kind of problem," Brody says.

The Cleveland Clinic approach
Nonetheless, the opportunities are vast for healthcare providers who are able to harness existing genetic expertise.

At Cleveland Clinic's Genomic Medicine Institute, for example, patients can receive personalized genetic healthcare for diseases ranging from cancers to cardiovascular diseases.

Charis Eng, MD, PhD, chair and founding director of the institute and a cancer geneticist, estimates that one-third of the patients in her subspecialty self-refer, while the rest are referred by other physicians. "We firmly don't discriminate," she says. "Often I'm pleasantly surprised that patients are smarter than their doctors and they recognize that they could be at genetic risk for disease A or disease B and they refer themselves."

Approximately 40,000 patients have benefited from personalized genetics visits during Eng's 11 years at the Cleveland Clinic, she says.

That said, there is a screening process patients undergo before genetic testing. The web-based screening tool, which Eng invented, she says, collects the patient-reported family health history, uses algorithms to assess risk, and pushes clinical decision support through the EMR to primary care physicians.

Patients deemed to be at genetic risks comparable to that of the general population can at that point receive reassurance with no further testing, while those at higher risk can be referred to the genetics department.

"We built the clinical practice so that we can see patients on the same day if necessary," Eng notes. "And that is rare in genetics in the country."

That access is possible because the team, made up of 2.5 full-time equivalent physician geneticists and nine FTE genetic counselors, is spread over several clinics throughout Cleveland Clinic's main campus and beyond. The team also practices some telehealth, which it plans to expand, and conducts shared medical appointments to address certain issues, such as predictive testing for a known mutation in a family member.

Addressing the DTC market
In some cases, patients visit the Cleveland Clinic with direct-to-consumer (DTC) genetic test results in hand. Eng and her team developed their strategy for managing the DTC factor when awareness of companies such as 23andMe began.

The first step focused on physician education. "The primary care doctors were afraid that patients would walk in and have this genetics test results document and they would have no idea what to do with it," Eng says. Eng and colleagues over seven months arranged seven continuing medical education presentations at various Cleveland Clinic locations with healthcare providers from primary care and OB-GYN clinics to discuss counseling, conflicts of interest, and other matters related to what she calls "nonclinically actionable recreation genetics."

Next, Eng and her team provided the physicians back-end support by providing two types of genomic counseling to which patients could be referred. One type is an in-depth genetics session that goes into family health history and includes a thorough evaluation and counseling, Eng explains. "The second is what we call a genomic counseling executive summary."

With the latter, the genetics team evaluates a patient's DTC test results and—unless it spots something actionable—provides a high-level overview. "At the time, most of the things we saw were completely nonactionable."

Getting involved
There are numerous reasons hospitals may want to get into genetics services, but that doesn't mean that organizations should start offering full exome sequencing just because the technology exists, Eng says.

"The key is to employ competent, well-trained genetics professionals," she says. "We went to training to take that family history, to talk to the patient, to examine the patient to see if there are any clinical red flags that suggest one disease or another or whether it's time to order a panel of genes."

One solution is for organizations to partner with existing genetic medicine centers, Eng says. There are still licensing and reimbursement problems to be resolved in increasing use of telehealth, she adds, but she expects they will be resolved in time.

And as the field of genetic medicine expands, part of the NHGRI's mission is to ensure its promise isn't limited to individuals with the willingness or means to pay, Brody says.

"One of the things we worry a fair bit about is having this information easily accessible, and not just for people who can afford $2,000 out of pocket," he says. "We really want to have this be equal access and not make any kind of health disparities."