Jeffrey Fudin, PharmD, DAIPM, FCCP, FASHP
Dr. Jeff Fudin graduated from Albany College of Pharmacy & Health Sciences with a BS and PharmD. He is a Diplomate to the Academy of Integrative Pain Management, a Fellow to ACCP, ASHP, & FSMB, a member of several other professional organizations. He is CEO of Remitigate (remitigate.com), an opioid safety software development LLC. Dr. Fudin is a section editor for Pain Medicine & Co_Editor-A-Large for Practical Pain Management. He practices as a clinical pharmacy specialist (WOC) and director of PGY-2 pharmacy pain residency programs at the Stratton Veterans Administration Medical Center in Albany, New York and has academic affiliations with Western New England University and Albany Colleges of Pharmacy.
Let's look at pharmacogenetics.
Ever since cytochrome P450 was discovered in 1955, along with its role in drug metabolism, numerous variants or different versions of CYP450 isoenzymes with different metabolic capacities have been identified. The native CYP450 activity is determined by the genetic make-up of these enzymes and can be affected by drug-drug interactions, liver impairment, and age. Drug metabolism and the variability among patients in terms of drug response can sometimes be explained by the genetic variations within the CYP P450 enzymes. There are also several other phenotypical parameters that can be assessed that help justify dosing and predict response or lack thereof to analgesics, some of which include OPRM1 receptors and COMT.
For example, there can be 2 patients of the same gender, weight, height, and race on oxycodone ER 10 mg every 12 hours for a total daily dose of 20 mg. Patient A’s serum oxycodone level comes back as 15.1 ng/ml, while patient’s B serum oxycodone level comes back as 30.5 ng/ml. Both patients A and B are genetically tested, and the results are as follows:
|Patient A||Patient B|
|CYP3A4/3A5||Normal metabolizer||Normal metabolizer|
|CYP 2D6||Normal metabolizer||Ultra-rapid metabolizer|
Oxycodone is metabolized into its inactive metabolite noroxycodone by CYP 3A4 and into its active, potent metabolite oxymorphone by CYP 2D6. Patient B is an ultra-rapid metabolizer at CYP 2D6, which means that the concentration of oxymorphone will be higher in patient B than in patient A. This would explain why patient B’s serum oxycodone level is higher than expected and does not match patient A’s level.
As shown in the above example, the results of genetic testing can be used to explain unexpected serum drug levels and can be used as a tool to help guide future treatment. Although genetic testing can be extremely helpful, it is not always necessary. Clinicians must use their clinical judgment to determine which patients would benefit from a genetic test.
Recently, the FBI raided a genetic testing company based in Irvine, California, as part of a health care fraud investigation. The company, Proove Biosciences, was allegedly providing kickbacks to doctors who encouraged patients to use the company’s DNA test. According to the Pain News Network, physicians could make $144,000 a year in kickbacks from Proove Biosciences for promoting the use of its genetic test. Reportedly, patients were being pressured by these physicians who were receiving kickbacks to accept unnecessary genetic testing.
The opioid policy at one specific pain management facility in Montana stated, “all patients on dosing levels at or higher than the maximum policy dose MUST be submitted for genetic testing."
Not only were these patients forced to undergo genetic testing at this center, their insurance companies were being charged for the test. Patients receiving care at this center were under the impression that the genetic testing would be free of charge. Prescribers at this specific pain management center have been linked to the Proove Biosciences company. This recent investigation raises the ethical issues surrounding pharmacogenetics and genetic testing.
Consent, confidentiality, and inequality in health care are a few of the ethical issues surrounding genetic testing that should be addressed. Genetic testing should only be done with the consent of the patient and should not be required for access to certain pain management medications. As far as confidentiality goes, results of genetic testing should only be discussed with the patient and the health care professionals who are assigned to the case. Genetic testing can be a patient identifier and should therefore be considered protected health information under HIPAA and the Health Information Technology for Economic and Clinical Health Act.
Finally, the issue of inequality of health care should be considered when thinking about genetic testing. Genetic tests can be expensive, and not all patients can afford them. But though there are ethical issues surrounding genetic testing, it can be a great tool to customize patient therapy, if used appropriately.
Pharmacogenetic testing allows clinicians the opportunity to individualize medication therapy based on patient-specific factors, such as metabolism and genetic make-up. It can provide an explanation as to why certain therapies work better than others, the same drug may require higher or lower doses, and why some therapies do not work at all or are not well-tolerated. Overall, genetic testing provides the opportunity to customize and improve patient care, especially in the pain management setting.
It is disappointing that Proove Biosciences shed a negative light on genetic testing. Hopefully, the general population will recognize that that specific company and the practitioners involved are aberrations with low ethical standards. Genetic testing is a growing, promising field that can truly help improve patient care, if used appropriately.
The commentary was collaboratively written with Mr. Tyler Naginewicz, Dr. Kerry Archer, and Dr. Mena Raouf.
Tyler Naginewicz is a 2018 PharmD candidate at Western New England University College of Pharmacy in Springfield, Massachusetts, and has a bachelor's degree in pharmaceutical science. He is a pharmacy intern at CVS.
Kerry Archer is a PGY-1 pharmacy resident at the Stratton VA Medical Center in Albany, New York. She received her PharmD from the University of Buffalo (New York) School of Pharmacy and her bachelor's degree in chemistry from Fairfield (Connecticut) University.
Mena Raouf is PGY-2 pain and palliative care resident at the Stratton VA Medical Center in Albany, New York. He completed his PGY-1 residency at the VA Tennessee Valley Healthcare System in Nashville and his PharmD from the Albany (New York) College of Pharmacy and Health Sciences.