Health System Lab Is Genotyping To Identify Best Drugs for Patients

Pharmacogenomic tests for surgical inpatients

CEO SUMMARY: One essential element of precision medicine will be the regular use of pharmacogenomic testing to provide additional guidance to physicians when selecting the most appropriate therapeutics and optimal dose for each individual patient. Despite the reluctance of private payers and Medicare to reimburse for pharmacogenomic tests, Avera Institute for Human Genetics (AIHG) in Sioux Falls, S.D., has used pharmacogenomic testing over the past six years to support clinical care and improve patient outcomes.

PHARMACOGENOMIC TESTING is one of laboratory medicine’s new frontiers. Physicians and pathologists know that patients metabolize medications at different rates. Pharmacogenomic testing is also expected to play an integral part in personalized and precision medicine.

Yet today, few health systems gather this information on every patient, due partly to the cost of genotyping and partly because research into the clinical value of this information is ongoing.

As most clinical laboratory scientists know, currently few health insurers pay for such testing. In 2015, the federal Centers for Medicare and Medicaid Services stopped paying, saying such assays were screening tests. Despite these concerns, Avera Health, a health system in Sioux Falls, S.D., has put itself at the forefront of personalized medicine.

The health system’s largest hospital, 545-bed Avera McKennan Hospital and University Health Center in Sioux Falls, performs pharmacogenomic testing on all surgery inpatients. The tests determine how well these patients metabolize pain medications.

In addition to inpatient surgical pain patient testing, AIHG also performs pharmacogenomic testing for psychotropic, anti-platelet, statins, and other medications. AIHG staff work with Avera McKennan providers and the pharmacy department to gather information that proves to be useful for about half of the patients tested, especially when evaluating the drug-drug-gene interactions.

“Avera Health seeks to determine the economic value of pharmacogenomic testing to a health system,” stated Krista Bohlen, PharmD, the Director of Personalized Pharmaceutical Medicine at the Avera Institute for Human Genetics. A research pharmacist on the genetics research team, Bohlen said Avera is collecting data on the cost effectiveness of the program and is planning to publish those results in a peer-reviewed journal this year.

Avera’s interest in pharmacogenomics testing began in 2006. “Since then, we have regularly pursued genetics research opportunities by genotyping human subjects involved in registries and other projects,” explained Bohlen. “Then, in 2009 and 2010, we added a study for pharmacogenomic testing for psychotropic medications for behavioral health patients.

CLIA Certification

“We started a research protocol for testing CYP2C19 for the antiplatelet agent clopidogrel in 2011,” she said. “Next, in 2013, the AHIG lab earned its CLIA certification and we started performing clinical pharmacogenomic testing for pain patients.

“Our administration recognized the potential of pharmacogenomic testing to improve patient care and to reduce costs through quicker treatment success and fewer adverse effects,” Bohlen added.

Early work on pharmacogenomic testing was funded by Avera Health, through a desire to promote research and recognition that someday, such testing would be reimbursed. “We pursued research to show the value to treating physicians, along with patients and researchers,” Bohlen said.

Seeing the potential

By 2013, Avera reached the important milestone of placing pharmacogenomic testing results into Avera Health’s electronic me ical record system [Meditech]. “Now, treating physicians had that data at the point of care,” said Bohlen. “This meant our lab test results could have clinical impact in real time versus the retrospective research we’d done up to that point.”

Three studies are underway involving patients with depression who were tested with Avera’s psychotropic genotyping panel. These studies include information about clinical outcomes from the EMR as well as data from validated patient questionnaires.

“We hope to show how appropriate use of pharmacogenomic testing improves patient outcomes,” emphasized Bohlen. “Along with improved patient outcomes, we hope to demonstrate that such tests also reduced the overall cost of care for these patients.

Multiple Co-morbidities

“With depression patients, there are often multiple co-morbidities,” she observed. “Thus, for our studies, we started with depression patients who fit certain criteria—meaning those who would not have many confounding effects from other medications.”

“To do all this, a team was assembled that includes clinicians from pharmacy, the clinical laboratory, a nurse practi- tioner from clinical implementation, a nurse-project leader and a variety of other staff,” noted Bohlen. “These are the people who implemented our program of pharmacogenomic testing for individual patients in the specific clinics. We have a significant opportunity to improve care in the 300 Avera hospitals, clinics, and other facilities in our five states.

“Researchers have looked at the impact on patients when they undergo a panel of tests for depression,” she added. “Our studies intend to add to that research by answering these questions: Do these patients get better; meaning is there an improvement in their depressive symptoms? And, how often do patients get put on the right medication?

Selecting right Medication

“Pharmacogenomics is a tool that helps clinicians to narrow their choices for medications from as many as 20 or more down to maybe eight to 12 medications,” Bohlen said. “Such testing allows physicians to target the right medication for each patient while doing their best to avoid adverse effects.

“Once our laboratory reports the test results, then physicians follow the dosing guidelines published by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and Pharmacogenetics Working Group of the Royal Dutch Association for the Advancement of Pharmacy,” she said. “In addition to these guidelines, we also evaluate primary literature.”

Avera’s journey to bring pharmacogenomics testing from research to bedside was not without challenges. Laboratory Operations Manager Trisha Lauterbach, MLS (ASCP) CM, CHT (ABHI), said one early challenge was implementing a smooth transition from paper orders to electronic test orders. Other challenges overcome included: entering structured lab results into the EMR, managing a clinically useful turnaround time, and developing clinical decision support that used flags triggered by new lab test results and the medications being ordered.

overcoming hurdles

A key hurdle was logistics. “Any pharmacogenomic testing program like this needs a rapid turnaround of results from the lab,” Lauterbach explained. “For example, if the specimen is collected by 8 a.m., our lab would want to deliver the results by that afternoon or—in some cases—within 24 hours so the results are available to the physician at the point of care.

“To do this, our lab does the genotyping and then enters the result into the EMR so that the physician knows the recommendation for which medications may be best metabolized,” she explained. “Having this information in the EMR means physicians can take this action without having to go outside of their normal workflow.”

Bohlen continued, “This allows the doctor to get the patient on the right medication that same day. We want the patient to be stabilized and make sure the medication is effective for pain before the patient is discharged, especially in our efforts to prevent readmission,” she said.

“In addition, we had an EMR system that wasn’t initially designed to handle pharmacogenomic results,” noted Bohlen.

Avera McKennan Health’s Molecular Lab Team Gets Positive Feedback Directly from Patients

RESEARCHERS AT THE AVERA INSTITUTE FOR HUMAN GENETICS are collecting data to use in peer-reviewed studies that demonstrate the value of the institute’s pharmacogenomic testing program. Later this year, they plan to publish the data.

In the meantime, the staff has been collecting testimonials about the value of pharmacogenomic testing from patients themselves, stated Krista Bohlen, PharmD, the institute’s Director of Personalized Pharmaceutical Medicine.“We see patients who need a knee replacement and maybe they’ve already had one knee replaced,” added Bohlen. “These patients may be worried about having another replacement surgery because the pain was so bad the first time. They tell us that the pain medications they’ve had in the past have not worked well.

“This is where the pain genotyping panel is useful to identify the best medication for these patients,” she stated. “Following the surgery, they tell us how surprised they were that the medication we prescribed was more effective for them. They will say things such as, ‘So this is what actual pain relief is like!’“It’s a similar experience for patients who have depression,” continued Bohlen. “Physicians outside of Avera Health might have tried up to eight different medications and still had poor results. But then when we run our psychotropic test panel, we can help choose the most effective medication and avoid adverse effects. This testing helps us to get to treatment success sooner for these patients.”

“To resolve that, our EMR analysts implemented results reporting and clinical decision support alerts into the workflow for providers.

“Today, we have alerts built into the EMR so that it operates as a clinical decision support system,” commented Bohlen. “For example, if a provider tries to prescribe a medication that is inappropriate based on the pharmacogenomic test result, the system will issue an alert with alternate recommendations.”

a reimbursement Challenge

Fair reimbursement was another hurdle to overcome. “The theory behind this program is that there are benefits to doing preemptive pharmacogenomic testing, but a big barrier to such testing is getting health insurance companies to pay for these tests,” observed Bohlen. “For that to happen, we need more data on patient outcomes and further data to confirm that testing helps prevent adverse drug events.

“Second, we need to demonstrate to payers that clinicians used these tests to put patients on the recommended medications,” she added. “With such data, health plans may be more willing to pay for these tests.

“Right now, health insurers don’t pay for pharmacogenomic screening tests,” Bohlen said. “So we also have to work through prior authorizations if the drug we identify as being the most appropriate for that particular patient is not on their list of approved medications

“If the patient’s insurance company doesn’t recognize the alternate medication as a tier-one drug, then it might not pay for the prescription or charge a higher co-pay or co-insurance,” noted Bohlen. “We use our specialty pharmacy patient advocates to help identify the anticipated co-pay and coverage to help the clinical team decide which medication to pre- scribe given the financial barriers.”

A significant part of Avera’s journey was improving efficiency and reducing cost. To accomplish that, the lab changed its testing protocol. “We started using polymerase chain reaction (PCR) testing instead of microarray technology,” Lauterbach explained. “Microarray provides significantly more data, but the turnaround time can be up to five days and is costlier.

Timeline for Avera’s PGx Test Initiative

FOR MORE THAN 10 YEARS, MOLECULAR GENETIC testing has been performed at Avera Institute for Human Genetics. Here is a timeline for this innovative program.

2006:
AIHG is founded. Funding is from a federal grant. Institute works with Netherlands researchers to learn how environment and genetics affect the development of certain traits and diseases among twins.

2009:
Initiates pharmacogenomic testing research study involving psychotropic medications for behavioral health patients.

2011:
Initiates research study with phar- macogenomic testing on patients who were prescribed clopidogrel, the anti-platelet medication.

2013:
Initiates research study with pharmacogenomic testing for pain patients. CLIA certification.

2014:
Clinical pharmacogenomics launched with scanned lab results and per- sonalized pharmacogenomic reports in the EMR.

2015:
Initiates electronic ordering, structured lab results, and clinical deci- sion support alerts in the Avera EMR. Initiates pharmacogenomic testing for pain medications for all surgical inpatients at Avera McKennan.

2016:
Obtains CAP accreditation. Providers regularly order clinical pharmacoge- nomics testing for pain, psychotropic, and anti-platelet medications.

2016:
Avera Institute for Human Genetics partners with The Netherlands Twin Register (NTR) to expand scientific collaboration between Avera and VU to learn how environment and genetics affect the development of certain traits and diseases among twins. Avera Twin Register, South Dakota’s only genetics registry of twins, is launched.

“With PCR, the turnaround time is 24 hours and the cost is significantly less than microarray,” she noted. “That’s a big difference because PCR enables us to do the testing almost in real time at a fraction of the cost.”

Bohlen agreed, explaining that the cost of testing was one of the biggest challenges the team faced initially. “Now that the costs are going down and this testing is more comparable to the costs of other lab tests, reimbursement is not such a significant barrier, especially if patients are willing and able to afford out-of-pocket costs if insurance denies the claim,” she added. “We are continuing to monitor the advantages that can accrue to the patient and to the health system as well.”

a Need for Collaboration

“To get the whole process to work efficiently, AIHG needed to develop a multidisciplinary approach to delivering care,” said Lauterbach. “As an example, for inpatient surgeries at Avera McKennan, pain genotyping blood samples are drawn in the morning on the day of the surgery and resulted by that afternoon. We enter the structured laboratory results into the EMR and our team then interacts with physicians and pharmacists on the pain team.

“In that way, there’s a lot of interaction—or a lot of passing the baton, if you will—from the laboratory staff to the pharmacy staff; then to the patient’s physician and clinical pain team,” she said. “The clinical implementation strategy is the key factor to making this work.”

“Our multidisciplinary team allows us to improve patient outcomes during the patient’s hospital stay by implementing the results, monitoring the alternate therapy, educating the patient, and ensuring the patient can afford the alternate medication in the outpatient pharmacy setting,” added Bohlen.

Benefits of Integrated Care

“Our lab can affect care quickly because we bundle the pharmacogenomic test panel with other testing the patient needs immediately before surgery,” noted Bohlen. “It’s a big benefit for Avera to be a completely-integrated health system.

“Our laboratory is available to do everything from the most basic molecular genetic tests to whole genome sequencing. And it’s right in the same hospital and health system, so we can deliver the results into the EMR in real time. Our tests are not being sent out so we don’t have all that additional overhead or intermediate cost.”

As with any multidisciplinary program, communication and education are critical components.

“Educating all providers in the value of pharmacogenomics and how to utilize results is needed to ensure that these tests are ordered and used in patient care,” Bohlen said. At Avera, education for providers started with discerning which patients would benefit the most and how they would benefit, how to find the lab results and discussing recommendations with patients, what strategies to use for patients with significant polypharmacy, and then evaluating the insurance and reimbursement strategies.

elements For Success

“Ultimately, we can have tremendous science behind it,” concluded Lauterbach, “but this program will not work if the turnaround time is too long, if providers don’t know how to use or find the results, or if they have to pass along a cost of over $1,000 to the patient.”

The decade of experience in research and the clinical use of pharmacogenomic testing is why the teams at Avera Institute for Human Genetics and Avera Health are demonstrating that this testing does contribute to improved patient care.

Avera’s Genetic Institute Joins Twins Research Program

WHEN THE AVERA INSTITUTE FOR HUMAN GENETICS (AIHG) was established in 2006, it began developing key collaborations, the first of which was the Netherlands Twin Register (NTR).

In the late 1980s, researchers at the Vrije University in Amsterdam started one of the first biobank efforts. The Netherlands Twin Register (NTR) was established in 1987 and designed to provide insight into how genetics and the environment influence individual differences. The NTR examines the contribution of hereditary predisposition to such characteristics as personality, development, disease, and risk factors for disease.

Since the NTR began, over 7,000 sets of twins between ages 15 and 70 and 28,000 sets of twins between birth and age 15 have registered. “In fact, the Avera Institute for Human Genetics started with a federal grant and worked with Dr. Dorret Boomsma and researchers from the Netherlands Twin Register,” Bohlen told THE DARK REPORT. Through this partnership, AIHG has analyzed thousands of DNA samples from the NTR.

Last year, the institute announced a new partnership with the NTR to expand the scientific collaboration between Avera and VU to learn how environment and genetics affect the development of certain traits and diseases among twins. As part of this new partnership, the institute also started the Avera Twin Register, South Dakota’s only genetics registry of twins.

Contact Krista Bohlen, PharmD, at 605- 322-3050 or krista.bohlen@avera.org; Trisha Lauterbach, MLS, at 605-322-3091 or trisha.lauterbach@Avera.org.

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