Part II of IV: Precision Medicine and Pharmacogenomics. How pharmacogenomics is improving patient care

Transcription

1 Part II of IV: Precision Medicine and Pharmacogenomics How pharmacogenomics is improving patient care March 2018

2 Author Kelly Chillingworth, RPh, MHA/Ed, CGP Senior Pharmacy Consultant Lockton Benefit Group Pharmacogenomics is the study of a patient s specific gene set to predict their response to a medication or medication class. It is not the prediction of the likelihood of disease development or progression, but simply a report of how a medication will work in a patient s body when treating a previously diagnosed condition. It is important for patients, health plan members, employers and payors to understand the difference between genetic testing as it applies to disease predisposition and this application of genetic testing to predict a body s response to a drug. 2

3 Combating adverse drug reactions Precision Medicine and Pharmacogenomics March 2018 The educated public likely understands the Food and Drug Administration (FDA) requires drug makers to submit data and studies before a drug can be approved, marketed and sold for use in a specific disease population. The process is thorough and can take many years from the point of molecular development through FDA approval. Despite this painstaking process, the prescribing community still must make their best guess or judgment call regarding drug therapy to find the right drug for the right patient at the right time. The goal is to treat the patient with the smallest amount of drug to limit side effects, maximize adherence and achieve the best clinical outcome. With so many well-trained, well-intentioned healthcare providers and so many novel drug choices, what could go wrong? The FDA cites studies estimating there are more than 2,216,000 serious ADRs in hospitalized patients, causing over 106,000 deaths annually. If true, then ADRs are the 4th leading cause of death ahead of pulmonary disease, diabetes, AIDS, pneumonia, accidents, and automobile deaths. The FDA goes on to note one out of 5 injuries or deaths per year to hospitalized patients may be as a result of ADRs. Finally, a two-fold greater mean length of stay, cost and mortality has been reported for hospitalized patients experiencing an ADR. 1 It is counterintuitive that a therapy intended to treat or cure a condition can cause a devastating and uniquely new situation for that patient. It is also incredibly disappointing when the subset of adverse drug events (ADEs) that could have been prevented occur despite controls in the healthcare system. As reported by the US Department of Health and Human services, ADEs account for nearly 700,000 emergency department visits and 100,000 hospitalizations each year. 2 ADEs account for nearly 700,000 ER visits AND ,000 Hospitalizations PER YEAR. 2 To combat the prevalence of ADEs, healthcare practitioners need to find and implement additional controls and safety measures, including the use of pharmacogenomic testing prior to the selection of a drug for patient consumption. Prescribers, nurses and pharmacists are trained to care for other human beings, to do no harm and to use all available information to make decisions regarding patient care, diagnostic accuracy, drug selection and drug administration. However, the reality is there are more than 10,000 prescription medications on the market, and nearly one-third of adults in the US take five or more medications. 2 As patients age, medication load increases as well as the risk of drug-drug interactions, drug-disease interactions and ADRs caused by decreased drug clearance and metabolism. To mitigate drug error risks, the most progressive healthcare facilities employ collaborative care teams, dual signoff on prescriptions and drug administration, and a rounding clinical pharmacist who accompanies prescribers during the assessment and prescribing phase to assist with drug selection and patient counseling. Even all these safeguards are not enough to prevent ADRs completely. Pharmacogenomic testing is one more important tool in the care team s toolbox. 3 Lockton Companies

4 Disease states impacted by pharmacogenomics Pharmacogenomic tests are intended to accomplish several things: Predict response to specific drugs and help prescribers select the right drug the first time. 3 Highlight the likelihood of side effects to specific drugs in specific patients prior to drug selection. Prevent wasting time and using unnecessary resources, especially in serious, timesensitive cases. Prevent complications from choosing an ineffective agent. The disease states most commonly impacted by pharmacogenomic testing include cancer, bleeding and clotting disorders, psychiatric disorders, and diseases with genetic mutations. A full list of categories is found in the table to the right. Common medications contained within these categories and well-known to the layperson include warfarin (generic Coumadin ), Plavix and tamoxifen. Pharmacogenomic testing of patients who need these common medications can help a prescriber know, prior to prescribing, if a person will respond appropriately and, possibly, if the patient will experience extreme intolerance or side effects. A complete list of all approved drugs with current guidance relative to biomarker links and pharmacogenomic testing can be found on the FDA website. The package labels of many new drugs on the market, numerous upcoming drugs in the pipeline and older drugs that have been on the market for decades now call for genetic or biomarker testing. Many of these are orphan drugs, or drugs used to treat rare conditions that occur in less than 1 percent of the US population. These therapies are targeted and very expensive. Payors and pharmacy benefit managers should reflect labeling parameters and prescribing guidelines in the coverage criteria to manage trend and appropriate drug spend. Therapeutic area* Infectious diseases Oncology Psychiatry Pulmonary Gastroenterlogy Rheumatology Neurology Inborn errors of metabolism Cardiology Dental Endocrinology Anesthesiology Dermatology Urology Gynecology Hematology Transplantation Toxicology Source: ScienceResearch/ucm htm

5 What are the barriers to the universal application of pharmacogenomics? A 2015 discussion among genetic experts states a main reason why pharmacogenomic tests are not universally considered in a physician practice is because the patient s genetic (pharmacogenomic) information is not available at the time of prescribing. 4 This barrier places patients at risk, as seen in the following example referencing Plavix (clopidogrel), a commonly prescribed blood thinner used prior to a stent procedure and for patients with a history or risk of clotting. CYP2C19, an isoenzyme in the cytochrome P450 system, has been suggested to be integral in the biotransformation of clopidogrel (Plavix ). Loss-of-function CYP2C19 alleles, carried by up to 30% of individuals, have been associated with increased adverse outcomes in clopidogrel-treated patients. 5 In other words, 30 percent of the US population cannot properly process Plavix and will experience adverse drug reactions, such as blood clots. This is an urgent concern since Plavix was in the top 50 drugs prescribed and filled in the US in Time is another barrier to the adoption of pharmacogenomic testing prior to prescribing. It takes the prescribing community time to adopt new technology and time to learn how to apply it. On average, new findings in healthcare can take 17 years to become a standard of practice. 7 It is hard to believe that a healthcare system as advanced as the US is still operating this way, but the reality of the situation is illustrated in the table to the right. LANDMARK CLINICAL TRIALS AND CURRENT RATE OF USE FOR SELECTED PROCEDURES Clinical procedure Flu vaccination Thrombolytic therapy Pneumococcal vaccination Diabetic eye exam Beta blockers after MI Landmark trial Current rate of use % % % % % Mammography % Cholesterol screening Fecal occult blood test Diabetic foot care % % % Source: A Balas, institute of Medicine, in Yearbook of Medical Informatics Lockton Companies 5

6 Pharmacogenomic testing is a new and imperfect science. It requires significant time, energy, effort and resources to learn about the science and how to apply it to a distinct population. In addition to the time it takes for the healthcare community at large to adopt new clinical procedures, another challenge surrounding the adoption of pharmacogenomics includes the sheer lack of time available for physicians and staff to spend on the tasks of learning and training. A primary care doctor in the US spends an average of 13 to 22 minutes with each patient and sees an average of 19 patients per day. 8,9 In 2002, family doctors reported having a panel of about 2,300 patients. 10, 11 These practitioners were polled years prior to the development and implementation of many of today s quality measures and certainly well before new and updated tests and procedures. The report stated that family doctors would have to spend 21.7 hours per day to provide all recommended acute, chronic and preventive care for a panel of 2,500 patients. 12,13 More recently, physicians have reported they spend, or waste, from 10 hours a week up to two-thirds of their time doing paperwork. 14,15 The baby-boom generation is predicted to grow the over-65 population by 55 percent by Patients over 65 can demand two to three times more healthcare services than a younger patient. Increased access to insurance through the Affordable Care Act has put additional demands on family practitioners. When the nation s aging population is combined with a shortage of primary care doctors, demands on physician time become harder to manage. With so little flexible time, it becomes difficult for providers to learn about and implement new practices and technology. This dynamic first played out in Massachusetts with the 2007 implementation of Commonwealth Care, a program resulting from an insurance mandate spearheaded by Governor Mitt Romney. While the uninsured rate in the state eventually fell below 3 percent, the program led to a 30- to 45-day wait for a patient to see a primary care doctor. Additionally, over half of Massachusetts physician practices could no longer accept new patients. Alice Coombs, president of the Massachusetts Medical Association, said it best, Insurance coverage does not equal access to care. 16 As potential changes to the Affordable Care Act play out in Congress, brokers and employers will need to pay close attention to the issue of access to care. Slow pharmacogenomic testing adoption may also result from the difficulty in turning pharmacogenomic test results into action items a physician s office can manage. Should the office test the entire patient population? Should just a subset of patients be tested? Who are the patients that should be tested? Will and should the patient receive genetic counseling prior to testing? Who writes the prescription for the test? 6

7 Precision Medicine and Pharmacogenomics March 2018 Pharmacogenomic test and lab vendors are becoming more sensitive to these questions and other barriers to the adoption of pharmacogenomic testing, and they are working hard to improve the processes, as well as the deliverables and reporting outputs. Conclusion The science is not perfect in every case, but in situations where it s proven to have a financial or clinical return on investment, physicians should strongly consider employing pharmacogenomic testing prior to prescribing drug therapies. 17 Pharmacogenomic testing is an exciting new tool for prescribers worldwide. Application of this science has the potential to be widespread and highly effective in helping doctors choose the right drug for the right patient at the right time. It is not intended to predict disease but instead to predict a patient s response to a drug used to treat an existing disease. Current reporting can be confusing and outside the scope of a physician s realm of experience. Also, adoption of any new healthcare technology and implementation in day-to-day practice takes years. Many payors are not currently covering pharmacogenomic testing, which forces payment issues and coverage decisions onto an individual or a self-funded employer group. Lockton is working with several vendors to find best-in-class partners for clients and will continue to educate teams regarding the options available in the marketplace. 1Scope & Cost of Adverse Drug Reactions U.S. Food & Drug Administration Preventable Adverse Drug Reactions: A Focus on Drug Interactions. 2Agency for Healthcare Research and Quality Patient Safety Network 3https:// 4Michael J. Knauer, Eleftherios P. Diamandis, Jean-Sebastien Hulot, Richard B. Kim, Derek Y.F. So. DOI: /clinchem Published September Michael J. Knauer, Eleftherios P. Diamandis, Jean-Sebastien Hulot, Richard B. Kim, Derek Y.F. So. DOI: /clinchem Published September https:// 7https:// ⁸Erin Brodwin and Dragan Radovanovic, Apr. 6, 2016, 1:12 PM. 9Bernstein, Larry. 5/22/ Erin Brodwin and Dragan Radovanovic, Apr. 6, 2016, 1:12 PM Bernstein, Larry. 5/22/14. see-each-day/?utm_term=.3543af4feefb 12 Erin Brodwin and Dragan Radovanovic, Apr. 6, 2016, 1:12 PM Bernstein, Larry. 5/22/14. see-each-day/?utm_term=.3543af4feefb Lockton Companies

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