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After DNA-10K, NorthShore Looks to Expand Genomics Integration Into Primary Care

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CHICAGO – NorthShore University HealthSystem has wrapped up its DNA-10K pilot to integrate genetic testing into primary care, and the five-hospital system is looking to expand testing to more clinics, in partnership with genetic testing firm Color and molecular clinical decision support technology vendor ActX.

Notably, the program demonstrated success in identifying patients at elevated risk for hereditary cancer and cardiovascular disease, as well as for enabling pharmacogenomics at population scale.

With patients' consent, results from the genetic testing are imported into NorthShore's Epic Systems electronic health records platform to inform clinical decisions. The Evanston, Illinois-based health system said this month that 99 percent of eligible primary care physicians ordered genetic tests for their patients. In an internal survey of ordering physicians, more than half indicated that the DNA-10K program provided a "direct clinical benefit" to their patients, according to the organization.

More than 99 percent of patients had at least one actionable pharmacogenomics-related finding from their tests, based on the ActX decision support database.

"We've learned that there's definitely interest from our patients, that a significant portion want to pursue this information and they want their caregiver, namely the primary care physicians, engaged in this process," said Peter Hulick, medical director of the Mark R. Neaman Center for Personalized Medicine at NorthShore. He said that DNA-10K's organizers were hoping for and mostly expecting exactly that.

"We believe that in order to really achieve our vision of having genomics integrated in the care of the patient, you have to be able to engage the primary care physicians," Hulick added.

NorthShore ran the pilot at 14 internal medicine, family medicine, and Ob/Gyn clinics from April 1, 2019 to Jan. 24, 2020.

DNA-10K launched as a partnership between NorthShore and Color to see if they could make genetic testing a routine part of primary care at population scale.

NorthShore and Color previously ran a pilot in which they signed up 1,000 patients in less than two months, representing an enrollment rate of more than 40 percent. However, about 60 percent of those who registered decided not to go through with the genetic testing, the partners said last year.

Participants in DNA-10K provided blood samples for Color to run a 74-gene next-generation sequencing panel in its CLIA-certified, CAP-accredited lab to identify variants associated with the risk of hereditary cancer, hereditary cardiovascular risk, and drug response. A low-pass, consumer-grade whole-genome test also looked for "recreational" information such as who might be genetically predisposed to experiencing a bad aftertaste from eating cilantro.

Color then returned results to patients via their primary care physicians. Patients in the program were given access to board-certified genetic counselors and pharmacogenomics-trained pharmacists to help them interpret results and develop personalized care and screening plans.

In January, Color and NorthShore announced that they had successfully enrolled 10,000 participants in DNA-10K. A survey showed that more than half the physicians who ordered testing said the results were clinically beneficial to patients. Additionally, patients expressed significant interest in DNA-10K, which may have played a role in attracting more than 800 new patients to the NorthShore system, Color estimated.

The organization recruited participants for DNA-10K by providing information about the testing opportunity through its NorthShore Connect patient portal for those coming in for primary care appointments.

Working with Color, NorthShore prepared two posters about DNA-10K for the American College of Medical Genetics (ACMG) meeting in March that was forced to go virtual because of the COVID-19 pandemic.

Of the more than 35,000 patients who had appointments for preventive care during that time, 81 percent opened at least one message regarding DNA-10K, NorthShore said in one of the poster abstracts. Half responded to express interest, and one-quarter, or 8,792, consented to a blood draw.

The testing found pathogenic variants in 462 patients, or about 8 percent of the 5,784 individuals who had results reported as of Feb. 20.

Amy Lemke, program director for outcomes research at the Neaman Center for Personalized Medicine, also has completed two studies on DNA-10K. One looked at DNA-10K patients one month and six months after receiving genomic test results, and the other assessed the experiences of primary care physicians, according to Hulick. Both have been submitted for peer review, Hulick said.

For pharmacogenomics, NorthShore has been a client of ActX since 2016, when the health system launched in-house PGx testing via a custom microarray panel and brought in the IT vendor to provide genomic clinical decision support.

Seattle-based ActX provides a genomic decision support system called GenoAct that is integrated into the Epic EHR to read the discrete data that Color sends from its sequencing lab. The hospital system loaded the genetic data onto the ActX platform after testing was complete on the 10,000 patients. By virtue of the integration with Epic, the data became available through the EHR.  

ActX CEO Andrew Ury called GenoAct a complex, customizable knowledge system that delivers real-time decision support based on discrete, machine-readable genetic data.

The ActX technology provides support on germline testing results, though NorthShore opted for just pharmacogenomics within the context of DNA-10K. In the program, every time a prescription order goes into Epic, ActX creates alerts if the patient's DNA screen indicates that the drug would not work or cause side effects.

"They were studying this population to see how doctors and patients reacted," Ury said.

The company has integrated with 10 different EHR vendors, Ury said, though NorthShore's DNA-10K was the largest project it had worked on.

Ury said that the experience helped the firm learn how to ingest large amounts of data quickly; at one point, the Chicago-area health system was adding data on more than 2,000 patients per day. "We certainly learned some lessons as we loaded thousands of people a day, but we had to make it easier for them to do it," Ury said.

ActX allows its clients to choose the alerts they want and to change the wording of alerts to fit institutional conventions. "NorthShore has probably done more customization of our content than most others," Ury said.

ActX relies on machine learning supplemented and verified by human curation. "Ultimately humans make the decisions on content," Ury said.

As a result of participating in DNA-10K, the vendor also was able to improve its own workflow.

Normally, a NorthShore clinician orders a genetic test through the EHR, then Color runs the panel and returns a result electronically. A copy of the result gets sent to ActX, adding the patient to the latter's system. But in the case of DNA-10K, the tests had already been run, so there was no new order.

"Rather than NorthShore identifying the patients in advance, we had to find a way to automatically recognize the patients and load them properly into Epic without the benefit of having an ordering event," Ury said.

Some of this technology is proprietary, so Ury was reluctant to discuss, but he said that the company wrote some new software to capture the data.

Once the names were in the system, the program ran smoothly, according to Ury.

"People are not yet widely delivering pharmacogenomics at scale," Ury said. "This is a demonstration that scaled quite smoothly from the point of view of the doctors, the patients, and the system to be able to show that you can handle thousands of patients a day."

Epic Systems released a genomics-specific add-on to its core EHR last year, allowing users to store discrete genomic data that could be actionable at the point of care.

For germline testing, NorthShore gets genomic coordinates of pathogenic or likely pathogenic variants in Epic as a discrete data element that the EHR vendor calls the "genomic indicator," Hulick said.

"We populate the genomic indicator for the germline result and then all the pharmacogenomic results," Hulick said.

"All those patients have genomic indicators assigned to each of the pharmacogenomic elements as well as any of the positive findings from the germline genes that were tested for in terms of inherited cancer or cardiovascular risk," Hulick said. "That's the whole key to driving these clinical pathways so that we can push out real-time information as [medical knowledge] is updated."

"The whole idea is: How do you reach patients globally in the health system as this information gets updated? We all know it's going to evolve over time both from the science and from our clinical understanding."

Looking back, moving forward

In 2015, NorthShore made a substantial commitment to precision medicine, including the opening of a pharmacogenomics clinic.

A decade earlier, NorthShore, back when it was a three-hospital organization called Evanston-Northwestern Healthcare, was among the first integrated delivery systems anywhere to adopt a single instance of Epic across multiple hospitals for inpatient as well as outpatient departments. Verona, Wisconsin-based Epic originally made its name in ambulatory care.

The organization also was one of the very first to reach the top of a scale from the Healthcare Information and Management Systems Society (HIMSS) that measures adoption of advanced EHR functionality. Swedish Covenant Health in Chicago, which joined NorthShore in early 2020, also was an early adopter, based on the HIMSS scale.

Since DNA-10K ended, NorthShore has looking at how to expand education about genomic testing and pharmacogenomics to patients and clinicians alike. The health system has about a dozen clinical champions representing internal medicine, family medicine, and Ob/Gyn, Hulick said.

Hulick said that he has heard numerous stories about patients learning that they had inherited a risk for diseases including various cancers and hypercholesterolemia.

"Now we can get them on the right care pathway," Hulick said. "It's not enough just to implement a program that gives access to testing. You have to continue to work on activating patients around this information, and that is a large focus of what we were doing" now.

NorthShore expanded its partnership with Color this year to 30 additional clinics and to include polygenic risk scores for type 2 diabetes and coronary artery disease. While testing within DNA-10K was free to enrollees, new patients have to pay $175 for this service. Color sells its panel online to the general public for $250.

Hulick said that NorthShore is trying to develop clinical pathways that incorporate genomic information, with the goal of better "activating" patients for preventive care and lifestyle adjustments. For example, women at elevated risk for hereditary breast cancer should be getting regular mammograms and breast MRIs.

"Just like people have health maintenance for a routine screening, we need that reminder and that engagement both on the provider and patient side, for situations that call for enhanced screening," Hulick said.

Hulick did note that plenty of people still have concerns about the privacy of genetic information. "We need to continue to educate on the benefits of having this information," particularly because the Genetic Information Nondiscrimination Act does not cover all risks, he said.

Some expansion plans got put on hold by the pandemic, but the fact that primary care clinics in Illinois were closed for routine care for nearly two months this spring allowed NorthShore's personalized medicine center to take a step back and assess its progress.

"Part of what COVID has allowed us to do is to begin this more structured program that we have for them to educate them on genetics more thoroughly and also about how this intersects with what we tried to do with DNA-10K," Hulick said. "Now as we come out of COVID, we can prioritize patients who need more acute screening earlier and get them into that protocol that they need."

DNA-10K did not incorporate family history, but previous research by the personalized medicine center did. Hulick said that he is combining learnings from both rounds of research to combine genetic testing with screening for family history in order to improve preventive care.

The organization also is trying to provide equal access to all populations at its facilities. The recently acquired and renamed Swedish Hospital on Chicago's North Side draws a different patient base than some other NorthShore facilities in affluent though racially and ethnically diverse suburbs.

"With our recent partnering with Swedish Hospital that's something that we're looking at to make sure we understand the communities we're in and how to approach them with something like genomics, which can be a daunting topic for some," Hulick said.

Although the program is no longer called DNA-10K, NorthShore is still going forward with the same procedures as it tries to make genomics an integral part of primary care.

"This is an ongoing commitment of personalized medicine. While certainly, and rightfully so, COVID has taken a lot of attention, we're still moving forward with this." Ultimately, Hulick would like to see how personalized medicine intersects with COVID-19 and other infectious diseases.