Pharmacogenomics (PGx) Overview & Counseling

Overview of Public Access to Genetic Testing & Pharmacist Counseling

• Categories of genetic testing and their purposes should be listed.
• Limitations of patient and healthcare provider access to PGx tests should be described.
• HCP roles in PGx based patient counseling should be distinguished.
• The pharmacist-centered counseling model and integration of PGx information into medication therapy management should be evaluated.
• The steps involved in a pharmacogenomic based patient counseling using an algorithmic approach should be correctly listed.

Integrating PGx

• A baseline understanding of the relevance of PGx should be obtained.
• Current understanding of supporting evidence related to patient care should be maintained.
• Willingness to provide genetic information for medication therapy optimization is important.
• The less reputable direct-to-consumer (DTC) options available should be distinguished.

HCP Education and PGx

• Minimum cursory knowledge is needed for application in clinical practice and patient education.
• Many HCPs are not comfortable with genetics but foresee its potential.
• Relevant HCPs in need of genomics education include Physicians, Nurses, Genetic Counselors, and Pharmacists.

PGx and Medication Therapy Management

• Pharmacists are medication experts, emphasizing the importance of dosage.
• Approximately 1.5 million preventable drug-related adverse events occur, costing > $177b related to death and injury.
• PGx is useful in preventing drug-related AEs like warfarin, clopidogrel, abacavir, and carbamazepine.
• PGx integration into current MTM paradigms is a logical extension to ensure the right medication for the patient and achieve the best outcomes, which is personalized medicine.

PGx Information Dissemination – Drug Labels

• Genomic data is found on drug labels.
• Reference the FDA Table of Pharmacogenomic Associations.
• About half of the labels refer to human normal or cancer genetic information.
• Most information concerns recommendations, not mandates, e.g., warfarin.
• Prescribers are not required to obtain PGx data, but guidance exists to help utilize it from CPIC.

Genetic Testing

• Genetic testing is performed/needed from professional and patient perspectives
• Patient perspective drivers include:
  • Identity-Seeking (Who's Yo Daddy?)
  • Disease Risk-Testing
  • Curiosity-Driven Testing/Searching for Better Lifestyle
• Professional perspective applications include various HCP ordered tests:
  • Pre-implantation genetic diagnosis (PGD)
  • Prenatal testing
  • Carrier testing
  • Predictive genetic testing
  • Diagnostic genetic testing
  • Pharmacogenetic testing

Public Access to Testing – Consumer and HCP

• Direct-to-Consumer (DTC) Pharmacogenomic Tests are commercially available.
• Proponents of DTC testing believe it increases health awareness, access to tests, patient privacy, and freedom of choice.
• Opponents highlight a lack of inclusion of HCP in the decision-making process, with patients ill-equipped to understand and interpret complexities.
• DTC Testing is Not Regulated, raising questions about counseling reliability and variability between companies' results.

Patient/Public Perspective

• Patients may be using the information to make decisions about relationships that are not based on medical advice

DTC Regulation

• Centers for Medicare and Medicaid Services (CMS) regulate clinical labs
• Food and Drug Administration (FDA) regulates test kits
• Federal Trade Commission (FTC) regulates false and misleading advertising
• State DTC testing varies: permitted, limited, or not permitted.
• Analytical validity assesses how well a test predicts the presence or absence of a variant.
• Clinical validity assesses how well genetic variants relate to the presence, absence, or risk of a specific disease.
• Clinical utility assesses whether a test provides useful information for diagnosis, treatment, management, or prevention of disease.

Example DTC Companies

• Healthspek
• Assurex
• PGT
• Harmonyx
• genesight
• 23andMe
• MILLENNIUM
• Navigenics
• genele
• DNA
• IDENTIGENE
• HOMEDNA
• kailos

DTC Testing Method

• Order a genetic testing kit from the kit or from your pharmacist.
• Follow the instructions included.
• Use included postal label to return the kit
• Send the kit back, wait and Interpret results

Testing Methodologies

• Refer to the Jackson Laboratory Methods Reference Paper.

When to Use and When Not to Use Methodologies

• Single Gene Sequencing
• Deletion/Duplication Analysis
• Targeted Mutation Analysis
• Multi-Gene Panels
• Whole Exome Sequencing
• Chromosome Analysis
• Chromosomal Microarray
• Fluorescent In Situ Hybridization

Interpreting the Results

• Calculation of "average population risks" differs for each company based on how they define the relevant population(s) on which to interpret relative risks.
• Different risk estimates are based on the gene chip used.

Interpreting Results – Step by Step

• Mr. Pectoris, a 70 y/o Caucasian male with DM2, HTN, and HLD, recently diagnosed with a STEMI, had a stent placed and started on Clopidogrel.
• His PCP, Dr. NoGenetics, receives a phone call from KnowYourGenes about Clopidogrel pharmacogenomic testing, and calls for help.
• Consideration is given to whether the test should be ordered, and how to use the results.

Considerations as A Pharmacist

• Check Pharmacogenomics Resources like Lexicomp and CPIC Guidelines for Clopidogrel recommendations based on CYP2C19 genotypes.
• Evaluate the PGx Test, considering general aspects and possible tests.
• Gene Association PPV represents the percentage of patients who test positive for the allele and will be affected.
• NPV represents the percentage of patients who test negative for the allele and will NOT be affected.
• Frequency of variant gene is categorized by race/ethnicity.
• Clinical Utility: What evidence exists to show that doing this test will improve patient outcomes?

PGx Testing Benefits

• CMS currently covers CYP2C19 and CYP2D6 on an evidence and case-by-case basis.
• CYP2C19 is medically necessary for patients with ACS undergoing PCI who are initiating or reinitiating clopidogrel (Plavix) therapy.
• CYP2D6 is medically necessary to guide treatment and/or dosing for individuals for whom initial treatment is planned with amitriptyline or nortriptyline for depressive disorders or tetrabenazine doses greater than 50 mg/day, or re-initiation of therapy with doses greater than 50 mg/day2.
• Pharmacy Benefits Managers often require prior authorizations, mostly for oncology drugs covered with concurrent results of Companion Diagnostic Tests (PharmDx, IVDs).

HCPs and Patient Counseling

• Physicians order tests, counsel patients, and exercise final medical judgment.
• Nurses treat, educate, provide advice, assist with sample collection, and administer/follow up on treatment.
• Genetic Counselors review patient history, translate complex information, and help patients deal with emotional aspects.
• Pharmacists are medication experts and incorporate PGx information to guide counseling and ensure safe use.

The Pharmacist and PGx Guided Counseling

• Pharmacists are well-positioned to counsel patients on medications affected by pharmacogenomics.
• Roles include collecting patient data, providing medication information, enabling understanding of requirements, and serving as advisors, with thorough counseling.

Pharmacist Directed Patient Counseling and PGx

• When PGx information available, can be logically incorporated into medication counseling. -For example: Your patient is a CYP2D6 PM and is being treated with a drug metabolized mainly by CYP2D6 and other alternatives exist

Integrating PGx Into Clinical Care

• Use a systematic approach to evaluate decisions about genetic tests / to apply PGx data.
• Utilize Algorithmic methods for evaluation, addressing two questions:
  • Is the drug necessary?
  • Are there alternative substitutes?
• If the answer to question 1 is NO, then there is little utility to testing.

One Algorithmic Method

• Is the drug necessary (Necessary)
• Is there an alternative therapy (Alternative)
• Is there a regulated Validated Test (Validated Test)
• What is Turn Around Time for Test (Turn Around Time)
• Is there appropriate evidence for results (Evidence)
• Is there appropriate HCP acceptance (Acceptance)
• How will the patient pay for the test (Reimbursement and Payment)
• How will you document test results (Evaluation and Documentation)

DTC Testing

• DTC testing can offer health-related information, ancestry data and fun personal facts.
• One area of DTC testing can be agreeableness, related to a polymorphism in the Clock gene, rs6832769
• Another area is having a great marriage, the OXTR rs53576 reveals marital satisfaction.

General

• Clinical documentation of PGx information is challenging to do.
• Other sections can apply e.g. DDI section for clopidogrel and PPI combo therapy based on genotypes.
• The solution is to develop a systematic process for each EMR and Dispensing System.
• Points to consider include if the question is right
• How to properly set up alerts for the clinic in regards to which medications and specific therapies.
• Consider which variants genes to test and how to test them.

Concluding Thoughts

• Pharmacists are uniquely positioned to counsel patients on medication affected by PGx, while physicians, nurses, and genetic counselors are also important.
• A systematic process for assessing PGx data is key to closing the gap between science and clinical practice.