The University of Mississippi Medical Center PGT Solutions And The University of Mississippi Medical Center

Who is MTL? Molecular Testing Labs Vancouver, Washington (360) 693-8850 www.moleculartestinglabs.com Medicare Approved Medicaid Approved (per State) CAP Accredited CLIA Certified Lab Director: Dr. Safedin Beqaj

What is Pharmacogenetic Testing? Pharmacogenetics refers to genetic differences in metabolic pathways which can affect individual responses to drugs, both in terms of therapeutic effect as well as adverse effects.[1] Pharmacogenetic testing is an outstanding opportunity to improve prescribing safety and efficacy. [2]  Pharmacogenetics is a very useful and important tool in predicting which drugs will be effective in various patients from all backgrounds, ages, and ethnicities. [4] In summary, here is a clear and concise explanation to your doctors or nurse practitioners: “ Our report gives you (the Dr. or NP) a definitive interpretation of how your patients metabolize the prescriptions you write for them.”

When is the best time to utilize PGT? Misconception: Q: As fellow sales representatives, we are often asked by physicians and nurse practitioners, “Who are the potential subjects and when is the best time to test the patients chosen?” A: Every person is a potential subject. Depending on personal insurance coverage, ALL persons should be tested. Because the patient’s DNA is tested, the patient pool can begin at 1 day old! Some doctors may imply they will only test their poly-pharmaceutical patients. Do NOT miss the opportunity to encourage the physician to test ALL patients regardless of prescription consumption! Wouldn’t it be wise to have metabolization results BEFORE dosing and prescribing the patient!?

Why use Pharmacogenetic Testing? ADR’s Over 106,000 deaths and 2.2 million serious events caused by adverse drug reactions (ADR’s) from prescriptions given in accordance with FDA regulations in the US each year.[2] ADR’s are the 3rd leading cause of death in the U.S. [3] These ADR’s are also responsible for 5-7% of hospital admissions, lead to the withdrawal of 4% of new medicines and cost society an amount equal to the costs of drug treatment.[3] Estimates indicate ADR’s cost $177 billion dollars in direct health care costs every year in the U.S. [3] Estimates show 50% of medications are ineffective or result in severe reactions, including death. [2]

Adverse Drug Reactions Defined Three outcomes for therapy: It works! Normal Response It doesn’t work (efficacy) } Adverse Drug Response It is toxic (safety) } Adverse Drug Response ADR’s – Huge Healthcare Costs: $177 Billion annually…. Which is why our Federal Healthcare System supports the science behind PGT

The Science Behind Pharmacogenetics

Cytochrome P450 Enzymes The super-family of Cytochrome P450 enzymes plays a crucial role in the metabolism of most drugs.

Pharmacogenetics: Inside Out Roughly 92% of all prescriptions are processed through the liver by the Cytochrome P450 pathway. This is where the CYP450 substrates begin metabolization… Pathway: Correlate: CYP2C9 Cardiac/Psych/Epilepsy CYP2C19 Cardiac/Psych/Pain CYP2D6 Cardiac/Psych/Pain/ADHD CYP1A2 Acetaminophen/Psych CYP3A4 Cardiac/Psych/Pain CYP3A5 Cardiac/Psych/Pain/Epilepsy

Pharmacogenetics: Inside Out In addition to testing metabolization pathways, MTL also tests for Risk Factors. These factors identify the patients’ medication “Sensitivity” and/or “Risk” levels. Risk Factor: Correlate: VKORC1 Anticoagulation/Warfarin Factor II Thrombophilia Factor V Leiden Cardiac/Thrombophilia MTHFR Hyperhomocysteinemia SLCO1B1 Cardiac/Statin Myopathy COMT Drug Response/Alz/Parkinson ApoE Cardiac/Hyperlipidemia OPRM1 Drug Response/Pain

Testing by Specialty

Cardiology The drug Plavix blocks platelet reception and is the second best selling prescription drug in the world, however, it is known to warrant different responses among patients. [6] Studies have linked the gene CYP2C19 to those who cannot normally metabolize Plavix, which is given to patients after receiving a stent in the coronary artery to prevent clotting. [6] Stent clots have a high likelihood to result in heart attack or sudden death, fortunately it only occurs in 1 or 2% of the population. That 1 or 2% are those with the CYP2C19 SNP.[7] This finding has been applied in at least two hospitals, Scripps and Vanderbilt University, where patients who are candidates for heart stents are screened for the CYP2C19 variants.[8]

Psychiatry We can predict quite accurately which anti-depressant a patient will best respond to by simply looking into their genetic code. This is a huge step from our previous way of adjusting and experimenting with different medications to get the best response. Antidepressants also have a large percentage of unresponsive patients and poor prediction rates of ADRs. In depressed patients, 30% are not helped by antidepressants. In psychopharmacological therapy, a patient must be on a drug for 2 weeks before the effects can be fully examined and evaluated. For a patient in that 30%, this could mean months of trying medications to find an antidote to their pain. Any assistance in predicting a patient’s drug reaction to psychopharmacological therapy should be taken advantage of. [5]

Pain Management Most common pain medications require activation of the enzyme CYP2D6 in order to be effective. Almost 50% of the patient base in America have genes which alter the function enzyme; meaning almost 50% of all patients will have varying levels of metabolizing the medicines prescribed. Pharmacogenetics will allow the prescribers to alter the dosage regimens in order to optimize the efficacy and safety of the prescribed medicine.

Primary Care Too much emphasis in the PCP world is focused on “fixing” as opposed to “preventing”. With pharmacogenetic testing, the PCP world can better understand how, what, and how much a patient needs to be prescribed for various events (asthma, ADHD, etc.) per patient specific. [12] Better understanding our patients through pharmacogenetic testing has lead to better patient care, better outcomes/efficacy, lesser rates of ADRs, and lowered healthcare costs

PGT Review

Takeaway Points: Provides clinicians with data supporting which prescribed medications will be most effective (safe) and/or least effective (dangerous) in treating the patient’s illness Reduces the potential for ADR’s Alleviates costly “Trial and Error” experiments Potentially reduces the number of medications taken by the patient Provides clear “Dosing” and “Alternative Medication” guidance MTL offers the most informative panel reports on the market

Panel Reports

Sales Script

New Account Set Up

Supply Requests

Wrap Up: Q & A