NEW YORK (GenomeWeb) – A new project spearheaded by Genome British Columbia and the BC Pharmacy Association (BCPhA) aims to assess whether pharmacists can drive adoption of genetic testing among doctors and help provide patients greater access to personalized medicine.
Through the effort, called "Genomics for Precision Drug Therapy in the Community Pharmacy," Genome BC aims to study whether pharmacists can use their intermediary role in the healthcare delivery process by identifying when patients may benefit from pharmacogenomic testing and then work with doctors to facilitate testing and precision therapeutic decisions that improve patients' outcomes.
"This project really puts the pharmacist in a central position as the front line healthcare provider," Corey Nislow, study leader and associate professor at the University of British Columbia's Faculty of Pharmaceutical Sciences, told PGx Reporter. "This is the individual that has access to the [patient's] cardiology, oncology, [and] asthma drugs, and sees the whole picture and can provide an integrated information package back to the patient."
In this project, UBC researchers led by Nislow will focus on using genetic testing to personalize the dose of the anticoagulant warfarin. Estimated to cost $400,000, the funds for the study will come from Genome BC and BCPhA. "The pharmacy association really came to us and saw this as an opportunity," Nislow said. "There is an enthusiasm for this project from the patient side and the provincial [government] side."
In the first 18 months of the two-phase project, researchers will retrospectively test approximately 200 patients receiving warfarin for 15 variants associated with metabolizing the drug on an Illumina next-generation sequencing platform. "The goal of the project in the first phase is to really work out the details of empowering community pharmacists to inform patients about pharmacogenomics, what it can and can't do," Nislow said.
In this part of the project – in which one pharmacist from 20 pharmacies across British Columbia will participate – researchers hope to work out logistical details such as establishing procedures for sample collection, educating pharmacists on how to work with physicians and consent patients for testing, and gauging the validity of the NGS platform by benchmarking results against standard allele-specific PCR testing. Although pharmacists will collect samples from patients and researchers will sequence them for variants associated with warfarin metabolism, at this point in the project patients' data will be de-identified and used for learning purposes only.
"We're keeping this part of the project focused on warfarin variants because the goal of the project is not so much to gather as much pharmacogenomic information as possible on each patient, but to work out the process," Nislow said. "By focusing on the warfarin variants, it allows us to avoid all the thorny issues of incidental findings and everything that follows from that."
UBC researchers have access to data from 200 matched controls that they can compare against the patients taking warfarin and receiving testing in the study. Nislow said that researchers will also conduct economic modeling to figure out whether NGS testing and the involvement of pharmacists to identify genetic testing opportunities improves patient outcomes and lowers healthcare costs.
If the first phase proves successful, in the second part of the project UBC researchers hope to roll out the prospective genetic testing effort to include more pharmacists and patients. In this part of the study, researchers hope to actually inform patients' warfarin doses with the help of genetic testing and refine the protocols for how data from NGS testing can be used in this process. "The decision to use NGS was a practical one," Nislow said, noting that for the project researchers will be sequencing samples at a depth of 50x. "We have a number of exome and whole-genome sequencing projects underway at [UBC], so we have the infrastructure to do [the testing]."
Warfarin is a highly variable drug in that too much or too little of it can result in severe, and at times life-threatening, excess bleeding or clots. The drug is consistently at the top of lists for treatment-related adverse events require patients to visit the emergency room or be hospitalized. An analysis of medical claims for atrial fibrillation patients who received warfarin between January 2003 and December 2007 found that the cost per patient with warfarin-related intracranial bleeding was nearly $42,000 and more than $40,000 for each patient with a major gastrointestinal bleed.
Proponents of PGx testing believe that testing patients for warfarin metabolism markers could help healthcare providers administer the most appropriate dose more quickly. The US Food and Drug Administration updated the label for warfarin twice, in 2007 and 2010, informing doctors that patients with certain variants of CYP2C9 and VKORC1 genes may require adjusted warfarin doses when they start therapy. But warfarin genetic testing hasn't been widely adopted in the US due to limited availability of rapid testing, conflicting data from randomized controlled trials, and deficiencies in the healthcare system that have hindered providers from preemptively testing at-risk patients and storing the results for when they need to be initiated on warfarin.
However, Nislow and his colleagues are hoping that the more integrated Canadian healthcare system will be able to overcome these barriers and that based on the results of this project, researchers will be able to implement pharmacist-guided PGx testing for many more drugs beyond warfarin. This is another reason why they decided to go with an NGS platform. "We're not positioning this to look just at warfarin. The window for prescribing warfarin is probably a couple more years," he noted. Indeed, there are newer anticoagulants on the market that are more expensive than generic warfarin but without the severe dosing variability risks.
"If we have significant statistical confidence [in this project] with warfarin, then that'll give us confidence to go back to the exome data and re-query it for every additional drug that that particular [patient] might be prescribed," Nislow said. He couldn't at this point say which other drug/gene combinations researchers might consider reporting back to doctors and patients, but the data from this project may help Genome BC figure out what other PGx data should be reported to patients.
Ultimately, if this project is successful, Nislow hopes that other Canadian regions will employ similar pharmacist-guided PGx testing programs. "We're taking a data-driven approach," he said. "So, if the data say that this can be a benefit to the patient and a benefit to the cost structure of the healthcare system, I would hope that it rolls out nationwide."