DNA Sequencing for All? Pros, Cons & Questions From One Health System’s Foray Into Precision Medicine

In 2018, Geisinger launched a pilot population health genomic screening program offering free DNA sequencing to 1,000 patients enrolled in its associated insurance plan. The Danville, Pa.–based system’s longer-term goal is to extend the offer to all of its 1.5 million patients. 

The DNA sequencing program grew out of Geisinger’s MyCode Community Health Initiative—a precision health research project wherein patients have all of their genes sequenced. One part of the project—the Genomic Screening and Counseling (GSC) program—looks at 61 genes, including 59 described by the  American College of Medical Genetics and Genomics (ACMG) as “highly actionable or medically relevant.” When MyCode researchers detect changes in these genes, the information is confirmed in a clinical laboratory, provided to the patients and used in their healthcare, says Christa Lese Martin, PhD, Geisinger’s associate chief scientific director. 

Geisinger’s population health pilot program and its MyCode project are separate programs, explains Michael G. Lesko, DO, chief of cardiology for Geisinger’s western region and system director for preventive cardiology. “The goal of the pilot is to see what the return will be. Will we get a lot of patients we can act on and in the end impact their health and reduce their costs over their lifetime if we find something early? It’s an almost pure form of preventive medicine, while MyCode is a bigger research project.”

CVB interviewed members of Geisinger’s precision medicine team about their plans for the program, early insights and challenges as well as questions still to be addressed. The following are excerpts from conversations with Martin and Lesko; Amy Sturm, MS, Geisinger’s director of cardiovascular genomic counseling; and Megan McMinn, MS, LGC, a genetic counselor embedded in the cardiology division for the past two years. 

Why did Geisinger decide to invest in widespread DNA sequencing? 

Martin: Geisinger is an attractive site for genetics work for a couple of reasons. First, we’ve been using the Epic electronic health record since 1996, so we have more than 20 years of patients’ electronically documented health information. Second, the majority of our patients are from central and northeastern Pennsylvania—regions where people don’t move around a lot. 

When you’re studying genetic disorders, it helps to have intact families in the same healthcare systems, where you also have longitudinal data. Our chief scientific officer, David Ledbetter, PhD, who is a geneticist, saw the opportunity for a precision health program here. We had early success with the genomics screening and results aspects of our research. The information we obtained affected patients and their family members. When Dr. David Feinberg came on-board as our CEO in 2015, he saw the value and challenged us to go beyond research and extend the benefits to all of our patients. [Feinberg left Geisinger in 2018 for a position at Google.]

What are some challenges you’ve had to address?  

Lesko: The biggest thing is that this is all new science. We’re discovering things all the time and working through them. For example, protocols. How do we do surveillance on patients who have positive results but don’t have the disease? And you have to be aware that there will be patients who come in with positive testing but, by the nature of genetics, statistics and penetrance, won’t necessarily go on to have the disease. 

We also figured out that we needed more genetic counselors. We now have Megan practicing with us in cardiology. She helps us with MyCode results and clinical cardiovascular genetics referrals.

How many genetic counselors do you have now? 

McMinn: We have approximately 25 counselors. Many are clinical counselors by training who now also have a research aspect to their jobs. About eight of them are actively returning results to patients or seeing them in clinic afterward. 

What’s it like being a genetic counselor embedded in cardiology?

McMinn: It’s been wonderful, in part because Dr. Lesko has been a great champion for genetics. We need providers who are pushing for genetic counseling services and preventive care. We historically have treated disease once it happens, but medicine is shifting toward preventive care. To do that, we’re using genetics to try to catch individuals who are risk before disease occurs. It’s been a good experience to build provider relationships and share the care of patients receiving genomic results.

What’s involved in offering DNA sequencing in your clinics? 

Martin: Based on the success of the MyCode GSC program and its impact on our patients’ health, we launched genomic screening as part of routine clinical care in several primary clinics. Currently, our population health genomic screening test is focused on ACMG’s list of actionable genes—including many related to cardiac disease and cancer. 

Getting the clinics set up and operationalizing our processes is part of my role. It requires training the staff, preparing patient education materials and ensuring the physicians or other providers know how to offer the DNA test to patients who come in for routine appointments. It also includes the follow-up after the test is ordered—drawing blood samples and sending them to the laboratory—and then the process for navigating negative vs. positive results, with the genetic counselors getting involved to help the physicians disclose results to patients.

What support and education have you offered to help your cardiology clinicians get comfortable with genomics? 

Sturm: We’ve offered CME events for cardiologists to learn about all of the different genetic conditions that MyCode gives results for, which are the same conditions they are on the lookout for in their regular general cardiology clinics. But you can’t just give a presentation to a group of cardiologists and expect that they’re going to know everything they need to know, or that they’ll need going forward. It’s really about developing active, ongoing relationships. Having a genetic counselor embedded in cardiology has worked well. Megan is in clinic with them, helps them learn the red flags to watch for in clinical and family histories and then connect what they’re seeing to the patients with the genetic risk variants once results come in. Seeing patients together has gone a long way toward establishing a relationship between cardiology and genetic counseling. 

We’ve also integrated one-page “just-in-time” education about the risk conditions into Epic so that it’s right there in the EHR at the point physicians get new genetic risk results. When they open a risk result notification, they are able to see succinct specific management recommendations and education on the risk condition. It’s like a genetics resource center, with clinician education support at the point of care. Maybe they’ve never seen this MyCode genetic risk result before, but they still have easy access to information that gets them to, “Oh, these are the tests I might need to order next.” 

The other neat thing is encrypted texting, which allows clinicians to text one another and reach out with questions in a HIPAA-compliant way. For example, a nurse in clinic with a new patient who has a cardiomyopathy risk result might text me to ask, “Is the test I need to order to get this workup going to include an echocardiogram?” Our clinicians have access to genetics expertise to easily and quickly help them take care of each patient. 

Lesko: I look at it as something that has re-inspired me in my career because it is so new. I’m excited about the opportunities ahead of us, including the potential to pivot healthcare from the system where we just treat patients after they get disease. We are going to impact patients before they get the disease because we’ll know from genetic testing what their risks are.

MyCode is returning results on single genetic risk variants. In the future, we also could look at polygenic risk scores for certain types of disease, like coronary artery disease. When that starts to flow, there’s  potential to be screened from a genetic standpoint to give percentages—your specific likelihood of developing diabetes or breast cancer, for example. And then your provider could offer personalized precision medicine, directing you toward the screenings or lifestyle changes that will make the difference over your lifetime.  

What about the learning curve? How long does it take to learn the language of genomics?  

Lesko: We’ve been doing this for two years and are still learning. We have a lot of work to do, but we will get there. And the students being trained today will be so much better at it. It’ll come naturally to them. I suspect genetic testing will be as important to today's trainees as my stethoscope was to me.

What are the costs associated with offering free DNA testing? Is there a plan for return on the investment? 

Martin: We’re still figuring out some of the answers, but it helps that Geisinger is an integrated healthcare system with its own health plan. The plan’s administrators have been interested in how genomics might be used to keep our patients healthy. They awarded us a $1 million quality-improvement grant for the DNA sequencing pilot, and a private donation also is supporting the pilot.

How much will it cost per patient? In the long run, will we save healthcare dollars by doing this type of testing upfront instead of paying for chemotherapy or surgeries when patients get sick? These are among the questions we aim to address. 

Another thing that will help, particularly with the longer-term goal of testing all of our patients, is that costs are coming down as the technology improves. Our current methodology is exome sequencing only, which typically costs $500 to $600 per patient. As we plan, some guesswork is inevitable—could we get the price down to $200 per exome, or even $100? It becomes easier to accept when you’re in the price range of other types of screening tests. 

A lot is still unknown, but figuring it out with the first few thousand patients while partnering with our insurance company is a first step, one that lets us keep our fingers on the pulse of several moving targets. 

Any early takeaways? 

Sturm: One is that at least half of the individuals we’ve found to be at genetic risk for breast cancer didn’t previously know about their risk. Our program was able to identify that and return that information. It’s even higher for cardiovascular disease. The majority of patients at risk who have been shown to have cardiovascular risk variants hadn’t  previously had clinical genetic testing that had identified it. And one of the conditions, familial hypercholesterolemia, is associated with a very high risk for heart attack, stroke and premature death. We have several papers in the pipeline. 

Are there downsides to offering free testing? Does it open the door to unnecessary downstream testing?

Martin: That concern is one of the reasons we limited the pilot to patients enrolled in Geisinger’s health plan. We didn’t want any cascade testing to get passed on to other companies or to patients themselves. Our health plan has committed to paying for cascade testing. If there’s an indication for a family member, then the testing for the family member is paid for. 

Sturm: And research has shown that cascade testing for many conditions is cost-effective. You can identify a person with the risk and then identify his or her at-risk relatives, but you also can identify people who are not at risk and therefore don’t need any type of screening for that particular condition. You can release the right patients from screening. The idea, especially with a lot of cardiovascular conditions, is that it’s recommended to test in childhood or early adolescence because many can have onset in the pediatric or teenage years. 

The idea is that we can do cascade testing at young enough ages, identify people who have the risk and implement preventive care. In some cases, it’s as straightforward as taking a daily medication to bring the risk back to close to that of the general population. That’s how we could prevent severe outcomes like cardiac arrest and myocardial infarction, which are much more costly to the medical system and to society.

We’re conducting large, NIH-funded studies looking at a range of questions. For example, do individuals with cardiomyopathy genetic risk variants develop, or not develop, the disease? And we’re working with a Geisinger health economist to study the cost-effectiveness of this type of population health sequencing. 

In general, what has been the response of patients and families to the offer of free DNA sequencing?

Sturm: We’ve conducted qualitative interviews with patient participants, and overall they have responded favorably to receiving their results. Over 90 percent say they have informed family members of their results, and most responded that they were happy they received the results.

Martin: We’re receiving positive feedback from physicians, too. At first, physicians kept asking, why are you doing this? Until they had their first patient where we found a result. Then they saw how they, as physicians, were able to change healthcare management because of the genetic  finding. 

For example, a physician whose patient in her early 80s was found to have a change in the breast cancer gene asked, “Well, that’s interesting, but what’s it going to do for her health?” But then she showed up to get her results and brought her two daughters, and they each have children. It helped the physician realize it really is more about taking care of a family than an individual patient. That doctor now campaigns for this program because he sees how it is changing care—such as offering earlier screening tests for cancer to try and prevent disease instead of treating it. 

McMinn: For as many champions, there are just as many who are skeptical, especially when we are seeing individuals who haven’t yet had disease present. As we move along, we’re seeing more providers accepting genetic results, but we do have a barrier to push through until we have a good body of evidence for people who are genotype positive with negative clinical history.

Lesko: It also helps that Geisinger is an integrated healthcare system with a health plan. We’re all very aware that the success of Geisinger depends not only on our clinic but also on keeping our patients healthy. This is pure preventive healthcare. We’re finding patients before they develop disease and we’re able to help them, especially with the explosion of new treatments coming out of research like this. For example, we’ve been working on familial hypercholesterolemia. We really believe that with genetic testing and genomic risk scoring we could potentially cure coronary artery disease or vascular disease in our lifetime. That’s what we’re working toward.