Originally published Aug. 19.
The University of Florida's experience implementing a pharmacogenetic testing program for clopidogrel is becoming a blueprint for bringing personalized medicine strategies to the community healthcare setting.
A year ago, the UF Health Personalized Medicine Program launched a strategy in which all patients visiting its catheterization lab would receive a multi-gene test to determine whether they are likely to respond to the anti-platelet drug clopidogrel (Bristol-Myers Squibb's Plavix). UF researchers in partnership with Stanford University developed a custom chip based on Life Technologies' QuantStudio real-time PCR platform that interrogates seven CYP2C19 SNPs linked to clopidogrel response, and an additional 249 SNPs associated with a number of heart-related conditions and treatments (PGx Reporter 6/27/2012).
Test results related to clopidogrel response are stored in UF's health IT system and become a part of patients' electronic medical records. Then, if a patient has a genotype that indicates reduced response to clopidogrel, a UF physician prescribing the drug would receive a "best practices advisory alert" in the patient's EMR. Genetic test results for the other SNPs on the chip are stored with patients' consent for additional research and for future use in clinical care.
Approximately 12 months since implementing this program, UF has genetically tested 1,000 heart patients and has collected data on how having this information at the time has enabled doctors to make medical decisions that impact outcomes. According to UF, approximately 28 percent of those tested had a genetic variation for which cardiologists recommended a different medication. The university is planning to publish more detailed findings from the program in coming months.
In the meantime, UF has received a four-year, $3.7 million grant from the National Human Genome Research Institute to expand its own program so that doctors can learn to prescribe other genetically guided treatments, and to implement similar personalized medicine efforts at community healthcare centers across Florida. "If genomic medicine is going to work, it has to work in places besides an academic health center, or a university-based setting," Julie Johnson, director of the UF College of Pharmacy’s Center for Pharmacogenomics, told PGx Reporter. "So, how do we test those waters?"
Starting off, UF has decided to implement a PGx testing program focused on clopidogrel at two cardiology practices at Orlando Health, a private healthcare network serving 2 million residents in central Florida and thousands of international visitors. Clopidogrel PGx testing will be implemented for cardiac patients undergoing stent procedures.
According to Johnson, UF picked Orlando Health's cardiology practices as the first expansion sites because while they are part of a private community healthcare network, they have certain similarities with the university's system. First, and perhaps most importantly, Orlando Health has an EMR system in which patients' data is stored. "When we go to the community hospital setting that will be one of the criteria that we use to decide which hospital we implement [the genetic testing] program in," Johnson said.
Storing genetic testing results in patients' EMRs is a critical component of UF's personalized medicine program and likely a key reason for its success. In early efforts to implement PGx testing for clopidogrel and the anticoagulant warfarin, drugs which are often needed to immediately treat critically ill patients, by the time the genetic test results reached the doctor for personalizing treatment strategies, the medical decisions had already been made.
However, when implementing clopidogrel PGx testing within its system, UF made sure that the test was performed once a patient presented at the catheterization lab. Then, with a 24-hour turnaround of test results, the data were stored in the EMR, so the system would alert the doctors if and when they decided to administer clopidogrel to the patient.
"We do think [the EMR] is a crucial element. It can't just be doing the genetic test, providing that result back as a lab report," Johnson said. "After we've done the implementation for the year, we know that if that's all we did, it wouldn't really impact the care of the patient. For the most part, it's just not going to hit the radar of the cardiologist the way it does if we really link to the clopidogrel prescription and basically fire alerts to them about what they need to do as it relates to the genotype."
Additionally, Orlando Health, like UF, is a very large health system located in a big city. And although Orlando Health isn't university-affiliated, it does train medical residents. In fact, UF will first implement the genetic testing program within the cardiology practice at Orlando Health where some UF-affiliated cardiology fellows already work part of the time. "So, there is already a little bit of a connection with UF," Johnson said.
Still, Johnson is fully expecting hiccups and unanticipated stumbling blocks in plotting out a program in a community setting. When implementing the PGx testing program at UF, often the biggest challenge was aligning the various parts of a complex healthcare delivery system to work together toward a common goal: to integrate a new healthcare intervention as part of the standard of care.
For example, according to Johnson, UF worried most about the process of storing, analyzing, and retrieving the genetic testing data, and the university expended a great deal of effort to ensure that these bioinformatics aspects went smoothly. "It turned out to be not a problem at all. But that was probably because we spent a lot of energy and a lot focus on that," Johnson said.
But in the process of ensuring accuracy of the test and educating cardiologists, UF didn't spend as much time working with phlebotomists, the people who collect the very blood samples from patients for genetic analysis. "So, there was this new genetic test available and they were getting orders to draw blood for this test, but they didn't know what it was," Johnson recalled. "At one point, they thought that if [the test] was ordered over the weekend, they shouldn't collect [the sample]. I have no idea why they would think that, but it shows that there are lots of pieces of the healthcare system … that have to work and have to know what's going on to make [the genetic testing program] work."
Wayne Jenkins, president of Orlando Health Physician Partners and senior VP of Orlando Health, also predicts there will be unique logistical challenges in implementing clopidogrel PGx testing within its cardiology practices. The issues Jenkins expects will need to be addressed specifically within Orlando Health's system will likely have to do with how testing is done, how data is imbedded within patients' medical records, and how that information gets back to and is acted upon by the physicians.
"There are basic logistical issues when you want to institute any new process, whether it's genomic or otherwise," Jenkins said. "Then, the other challenge is to educate the physicians and the people acting upon the tests results, so they view that [new process] as the new standard and start utilizing that."
Generally, Johnson expects that doctors in the community setting may need more education around PGx testing than academic physicians who have had exposure to such testing through the research setting. Cardiologists at UF have grand rounds and conferences every week where they learn about emerging medical concepts, but the educational opportunities may be different for doctors within a large, private healthcare network. "That's part of the learning curve," Johnson said. "How do you disseminate this information for these people practicing in different settings, and is the way you do that different based on their schedules and how they receive new information?"
Implementation of PGx testing for clopidogrel outside of academic settings isn't without controversy. The US Food and Drug Administration in 2010 added a black box warning to clopidogrel's label alerting healthcare providers that people with certain CYP2C19 genotypes are 'poor metabolizers' of the drug and should be given a different dose or an alternate treatment. However, several large meta-analyses of cardiac patients prescribed clopidogrel have yielded conflicting conclusions about the association between CYP2C19 genotypes and clopidogrel response (PGx Reporter 3/28/2012). These studies have led some prominent cardiologists to assert that the FDA prematurely updated clopidogrel's label recommending genetic testing.
In general, UF's cardiologists have embraced PGx testing for clopidogrel. "There are definitely some who feel more negative about it, won't order the test, and don't feel that the level of evidence is where it should be for them to use it," Johnson said. "Overall, reception of [clopidogrel PGx testing] has been positive, but not 100 percent positive. We anticipate it will be similar as we move out to these other settings."
At Orlando Health, Jenkins also expects not all cardiologists will embrace PGx testing for clopidogrel. "Like anything, it's never a uniform opinion," Jenkins said. "There may be some that say that they absolutely want to do this and there may be others not ready to do that."
Another consideration when UF expands its PGx efforts out into community practices will be how to inform patients about genetic testing. At UF, before treating patients, healthcare providers garner their consent to receive clinical care from the hospital. Because PGx testing for clopidogrel is part of that clinical care at UF, there isn't a separate consent process for that specific testing.
"We went back and forth a lot on whether genetic testing would be part of clinical care, whether there would be a separate consent [process] for the genetic testing, and whether they would all be part of research," Johnson said. "We spent several months discussing this with our ethicists, with our cardiologists, and our institutional review board. In the end, we felt, based on the [FDA's] black box warning, based on the feelings of our cardiologists, the decision was that we [get the] consent our patients for clinical care, and we don't separately [get] consent, for example, for lab work."
The university has a research component that gauges additional SNPs associated with various cardiac conditions, and patients were separately asked whether they wanted to partake in that. Specifically, UF would ask some patients for permission to store their biological sample and information about other genetic markers for potential clinical use in the future.
According to Johnson, between 85 percent and 90 percent of patients UF asked to participate in research agreed to do so. Of those who didn't consent, a few opted out because they were unwilling to specifically engage in further genetic testing, but most just didn't want to participate in research, she said.
The consent process for implementing genetic testing will differ for each system, and this is something UF will have to work on with its partner hospitals. "It's possible that as we have conversations with Orlando Health, we'll come to a different conclusion" about how to consent patients for genetic testing, Johnson said. "We're not assuming that at every site they'll have the same attitude in terms of whether genetic testing will be part of clinical care."
Although Orlando Health hasn't yet decided its consent policy yet with regard to the PGx testing program, Jenkins anticipates that its cardiology practices will probably also consider PGx testing as part of clinical care, based on FDA's black box warning.
If the implementation at Orlando Health is successful, UF hopes to extend the genetic testing program into other community hospital settings. For example, Florida State University has a program to train medical students within a network of primary care physicians and smaller community care hospitals. Johnson and her team are hoping to select a community hospitals within this network to implement the clopidogrel PGx testing program.
"We're going to be taking everything that we learned and everything that we did … here at UF and really try to plot that into their health system," Johnson said. "We know that there will be certain challenges that are really unique to those health systems. But we also think that in many ways we've already done the hard part."