After the Human Genome Project was completed in 2003, the study of Pharmacogentics became popular. It was discovered that many patients metabolize differently, some 85+% of clinical medications travel down 5 pathways in the Cytochrome P450 family and a patient can metabolize normal, rapid, ultra rapid, slow or ultra slow, resulting in a widespread difference in therapuetic outcomes due to pharmacokinetics...
The PGx test was developed in 2004 which genotypes for metabolizer status, but the test cost some $300,000 and was simply not practice for the clinical setting.
Because of Next Generation Sequencing, the price of the PGx test was lowered in 2013 to the point to where Medicare, Medicaid (most states) and the commercial carriers now pay for the test!
Why? Why would most insurance companies within a year decide to pay for a one-time genetic test? To save money! The FDA estimates that the PGx test will save the healthcare industry over $136 Billion annually. Currently there are over 2.2 million adverse drug effects (ADE’s) annually resulting in over 106,000 deaths. ***93,000 of which are deaths occurred while a resident of a nursing home community! This has a higher cost than all cardiovascular and diabetic costs combined.
- 50% of patients with depression do not respond to the first treatment
- 30% discontinue treatment due to intolerable ADE’s
- 70% who receive medications for depression are nonadherent – with ADE’s being the most common reason
- 58% of patients receive relief from pain medications
- 30% of pain patients have a genetic opioid (GOMD) metabolic defect
- 700,000 patients are treated in ER as a result of ADE’s
- 9.7% of ADE’s cause permanent damage to patients
- $47 Billion in annual hospitalization costs related to ADE’s
- $76.6 Billion annual cost of drug therapy morbidity or mortality
Sources – US Institutes of Medicine and Journal of American Medical Association:
The PGx test gives actionable data to physicians using science to help eliminate ADE’s and improve patient outcomes by KNOWING (before prescribing) how each patient metabolizes and what medication to prescribe and at what dose – resulting in improved outcomes while saving the healthcare industry billions of dollars!
- The AMA calls it “The Future of Medicine“
- Vanderbilt calls it “Personalized Medicine“
- Cornell/Columbia call it “Precision Prescribing“
- Eli Lilly calls it “Tailored Therapuetics“
Why, within the past 18 months, does Cornell/Columbia, Georgetown, Harvard, Mayo Clinic, Stanford, Vanderbilt (just to name a few) all order the PGx test for their patients? Why has the St. Jude Children’s Hospital made it mandatory on all patients, as well as Vanderbilt for their cardiology patients? Why has the AMA made a non-marketing informational brochure on this topic and distributed nationally?
How does this benefit the patient and the physician?
We are all different! We have different DNA and respond differently to medications. Only 70% of Caucasians metabolize normally (the reason why many drug studies are performed in northern Europe). Some 40% of African Americans, 50% of Asians and 80% of Polynesians do NOT metalobize normally! Out of 100 patients in a waiting room, only 46% metabolize normally while 35% are intermediate, 13% are poor and 6% are ultrarapid metabolizers.
The PGx test saves the “trial and error” process (and saves money from ADE’s). It gives actionable data to the physician so the right medication at the right dose will be prescribed the first time to achieve the desired therapuetic results. As an example, the FDA has “black boxed” Plavix. Patients with reduced-function alleles have a 3.5-8 times greater risk for major adverse cardiovascular events. This can be prevented by simply ordering the test for each patient (there is no way of knowing how each patient will react to Plavix and there is a huge legal implication if a physician does not order the test).
This test will bring to pass “the goal to cut the cost of sequencing an entire human genome to $1,000 or less” (Francis S. Collins, M.D., Ph.D. – Director, National Institutes of Health).
The point of personalized medicine is to:
- develop better efficacy,
- better outcomes,
- fewer adverse events, and
- lower systemic costs.”
Example. The drug manufacturer of Coumadin has a table in the package insert indicating exactly how to dose based on the patient’s allelels. Question. How does a physician know what allelel the patient has inherited from mom and dad?
Answer. Order the PGx test (the only way to know).
Concern. Does this cost the patient money? For Medicare, (Medicaid in certain States) and some PPO patients the answer is NO... Some HMO’s do not cover the test, as well as patients who have not yet met their deductible. Most labs have a financial assistance program (FAP) which limits the out-of-pocket costs to the patient. This is a “one and done” test. The patient takes a summary of the test to share with every physician they may visit for the rest of their lives
QUESTION: Did you know that Adverse Drug Reactions (ADRs) are the 4th leading cause of death of Americans—ahead of pulmonary disease, diabetes, pneumonia, accidents, automobile deaths, and AIDS? (www.FDA.gov)
QUESTION: ...or that 1 in 5 injuries or deaths in hospitals are caused by ADRs...or that the cost of $136 billion/year is greater than the total cost of cardiovascular or diabetic care...or that the mean length of stay, cost, and mortality rates of ADR patients are DOUBLE those for control patients? (www.FDA.gov)
Ask your doctor if they are offering this simple, safe, and painless test. If not, ask us how easy it is to add it to their practice.
DOCTOR: Contact us to learn how you can enroll in a program to have your patients’ DNA tested to show how they will metabolize most drugs. There is no cost to you and no obligation. We make it very simple and easy for your practice and for your patients. No blood! Just a buccal swab.
FACTS: Serious Adverse Drug Reactions (ADRs) happen to more than 2 million Americans each year. They send 770,000 into the hospital. And 100,000 of them end in death—each year! (www.FDA.gov)
The majority of ADRs are caused by genetic variations that we can now detect.
WARNING: The only way to determine prior to drug administration whether a patient is an Ultra-Rapid metabolizer is by the use of a Pharmacogenetic DNA test ... We are NOT all the same!
Quotes From Others:
"The goal of personalized medicine is to individualize health care by using knowledge of patients' health history, behaviors, environments, and, most importantly, genetic variation when making clinical decisions.
American Medical Association
"The power in tailored therapeutics is for us to say more clearly to payers, providers, and patients - 'this drug is not for everyone, but it is for you.' This is exceedingly powerful."
John C. Lechleiter, Ph.D. President & CEO, Eli Lilly and Company
"Today, one of our biggest goals is to cut the cost of requencing an entire human genome to $1,000 or less. This advance will pave the way for each person's genome to be sequenced as part of the standard of care, leading to a revolution in the practice of medicine."
Francis S. Collins, M.D., Ph.D.
Director, National Institutes of Health
Pharmacogenomics has been characterized as "getting the right dose of the right drug to the right patient at the right time."
L. Lesko, Regulatory Perspective on Warfarin Relableing with Genetic Information
The concept of personalized medicine is not new: The practice of medicine has always been about treating each individual patient, and clinicians have long observed that different patients respond differently to medical interventions. What is new is that paradigmatic developments in scene and technology offer new promise for developing targeted therapeutics and tools for predicting who will respond to a medical therapy or who will suffer ill effects.
Margaret A. Hamburg, M.D.
Commissioner of Food and Drugs
U.S. Food and Drug Administration
Other Updated Information Regarding Pharmacogenetic DNA Testing!
STATISTIC: The CYP2D6 pathway is where many pain management and psych drugs metabolize. Only 55% of the population are Normal Metabolizers in 2D6—and 10% are Ultra-Rapid metabolizers! TEDxStanford
DRUG SEEKER: A patient who does not metabolize pain medications at the normal rate may be mis-classified as a “drug seeker” and draw the attention of DEA because of his/her complaints that the pain drugs are not working!
(Dr. Russ Altman at TEDxStanford)
LABELS: FDA and EMA (European Medicines Agency) require labels on hundreds of drugs regarding Pharmacogenetic testing being suggested, recommended, or required for those drugs. (www.PharmGKB.org)
PERSONALIZED MEDICINE: Pharmacogenetic testing is the foundation for Personalized Medicine, the end of the “one-size-fits-all” theory of medicine.(AMA)
FOLIC ACID: Much of our food is “enriched” with it; but a common MTHFR genetic variation renders many people unable to properly process (methylate) it resulting in numerous ailments that are often diagnosed incorrectly in the absence of the information we provide. Failure to recognize MTHFR mutations can have life-threatening consequences. FDA
INTERACTION: Some drugs are Inhibitors or Activators (Inducers) of other pathways and can reduce an Intermediate Metabolizer to a de facto Poor Metabolizer or elevate a Rapid Metabolizer to a de facto Ultra-Rapid metabolizer causing other drugs to fail to work or even to become toxic. (FDA)
FDA is encouraging the development of pharmacogenomic tests for use in optimizing pharmaceutical therapies.
(Guidance for Industry and FDA Staff: Pharmacogenetic Tests and Genetic Tests for Heritable Markers 3 )
RISK MANAGEMENT: Standard of Care based on custom (i.e., what other doctors are doing) is giving way...to a more objective 'reasonableness' standard...a jury might find in some circumstances that the current practice of all or most physicians in a certain context was below the SOC that could and should be achieved.
(Personalized Medicine. 2011;8(4):457-467)
LIABILITY: ...if a pharmaceutical company discovers pharmacogenomically relevant information during the FDA approval process and discloses that information in the drug insert, with a few noted exceptions, the requirements of the Learned Intermediary Doctrine are satisfied, and the liability passes to the physician. (UCLA Journal of Law & Technology)
MAYO CLINIC: The promise of Pharmacogenomics - providing the right drug, for the right patient, at the right dose.
(Mayo Clinic Public Service Announcement Video)
INTERACTION: It is important that PGx analysis consider drug-to-drug as well as drug-to-gene factors. (Pharmacological Reviews)
ADHERENCE: Pharmacogenetics can reduce unwanted side effects and thus improve patients’ adherence to their prescribed drug regimens. (Nature.com)
COMPOUNDING: In a research article published in International Journal of Pharmaceutical Compounding, the author emphasizes the importance of patients’ genetic information in compounding pharmacy. (Dr. C. Mailloux)
INFANTS & CHILDREN: Pediatric patients, especially all newborns and infants, are particularly at risk for experiencing drug-related adverse events. (PubMed, Fabiano V.)
INPATIENTS: In one year, 106,000 hospitalized patients die because of Adverse Drug Reactions (ADRs) though under the expert care of the hospital staff. (JAMA)
PEDIATRICS: ...adverse drug reactions (ADRs) in children can have a relatively more severe effect when compared to adults (NCBI)
DOWN SYNDROME: Mothers-to-be with MTHFR mutation should adjust diet to reduce risk of Down Syndrome. (Amer. Jrnl. Clinical Nutrition)
PERIOPERATIVE: Inadequate pain relief and adverse effects from analgesics remain common in children and adults during the perioperative period...and serious side effects from perioperative opioids occur frequently in approximately 50% of patients. (Medscape)