If four full 737s were crashing daily resulting in total loss of life, there would be a public outcry and immediate governmental intervention. Yet, we lose an equivalent number of people daily — 275,000 American lives annually — to adverse drug events (ADEs). This public health crisis largely goes unnoticed because it happens to one mother, one son, one sister, and one friend at a time in homes, clinics, emergency rooms, nursing homes, and hospitals. Outdated surveillance and reporting systems mean many more ADEs go unrecorded. Most ADEs occur when medications are administered and taken correctly, contrary to the popular belief that this is most frequently due to non-adherence. The impact is worse for women, who are twice as likely to experience ADEs, and for non-White patients. This is because clinical trials for the generic drugs we primarily prescribe were conducted years ago and mostly included only White males of European ancestry.
While some medication harm may be unavoidable, studies indicate that half or more can be prevented by prioritizing education, equitable healthcare access, and technology, which will require legislative action.
The growing public health crisis
In 2016, the last time it was measured, we spent $528 billion on non-optimized medication, a staggering figure that exceeds the cost of the drugs themselves or any major chronic disease. The more medications a patient takes, the higher the risk of ADEs. Currently, over 40 million patients take five or more medications daily. With the “silver tsunami” of baby boomers aging into Medicare, this number is expected to double by 2040. The time to act is now.
Despite investment in precision medicine, pharmacogenomics (PGx) testing is still underutilized as a tool for reducing avoidable medication harm. PGx testing helps determine which drugs and doses are likely to be safe and/or effective based on each patient’s genetic makeup. It is precision medicine for medications. Unlike other genetic variations that are usually uncommon, PGx variations occur in over 99% of patients. A single, comprehensive, multi-gene test can help maximize the safety and efficacy of many commonly prescribed medications used in mental health, pain management, cardiovascular care, cancer care, and more. Drug-gene interactions are very similar to drug-drug interactions – in fact, the FDA has stated in drug development guidance that they are similar in scope and should therefore receive similar attention. The key differentiator is unlike drugs, genetics cannot be altered.
Consider the 1,300 patients that die each year, not from cancer, but from the fluorouracil or capecitabine treatment itself. For 5-7% of patients with DPYD PGx variants, standard doses of these medications can be toxic with a 25.6 times increased risk of treatment related death. Or, consider the 8% of patients with certain PGx variations impacting citalopram and escitalopram metabolism that are 34.3% more likely to become suicide victims because the drugs are processed out too quickly to provide treatment benefit or so slowly that they increase adverse effects leading to treatment discontinuation. Perhaps also consider the patients who continue to receive clopidogrel without PGx testing despite an FDA black box, first added in 2010, warning that patients with certain PGx variants are more likely to have another heart attack or stroke.
The promise of PGx testing
Biomarker testing, including PGx testing, can help turn this tide. Numerous studies have confirmed that optimizing prescribing with PGx testing reduces emergency room visits, hospitalizations, and healthcare costs. A large trial in several European countries across various specialties and care settings showed a 30% reduction in clinically significant adverse drug events in just 12 weeks. A recent meta-analysis in adult cancer patients showed a 53% reduction in significant adverse events with use of PGx testing. And despite the lack of widespread adoption, medical liability risks are increasing when evidence-based PGx testing is not discussed with and offered to patients. So why isn’t it standard of care? Numerous hurdles stand in the way of PGx testing becoming the standard of care, including:
- Inconsistent insurance coverage: A significant barrier to equitable access and adoption of biomarker testing, including PGx testing, is inconsistent insurance coverage that has not kept pace with professional guidelines and advances in the evidence. This has led to further socioeconomic, racial, and ethnic disparities in accessing quality care.
- Lack of education and clinical decision support: Both provider and patient education and prioritization of integrated clinical decision support are necessary to realize the benefits of genomic medicine, including PGx-guided medication management.
- Pharmacists’ lack of recognition as healthcare providers: Although many states recognize pharmacists as healthcare providers, they are not yet acknowledged as providers at the federal level. This lack of federal recognition hinders reimbursement for pharmacists, despite their provision of numerous and essential direct-care patient services that align with their training, including PGx-guided medication management.
Support biomarker legislation and prioritize PGx education
To address insurance coverage barriers, biomarker legislation has been enacted in sixteen states including Arizona, California, Georgia, Illinois, Maryland, Texas, and New York, and introduced in eleven others. The National College of Insurance Legislators (NCOIL) endorsed model biomarker legislation in the summer of 2023, setting the stage for expected nationwide adoption. Typically, this legislation requires state insurance providers, including Medicaid and commercial payers, to cover tests that guide treatment decisions based on medical and scientific evidence including testing covered by CMS NCDs, Medicare Administrative Contractor LCDS, or nationally recognized clinical practice guidelines and consensus statements. Medicare LCDs have covered certain evidence-based PGx testing since 2020.
Clinicians must prioritize educating themselves about PGx testing and incorporate it into their practice to improve patient safety and care. Free resources can be found at NIH Inter-Society Coordinating Committee for Practitioner Education in Genomics (ISCC-PEG). Healthcare professionals in states that have not enacted biomarker legislation can learn how to support state efforts at ACS CAN.
Other legislative actions and advocacy efforts to improve drug safety and reduce ADEs are also in the works. They include:
- Right Drug Dose Now Act of 2024 – You can urge your congressional representatives to support this act – learn more and sign support at Fourth Cause. Reintroduced by Swalwell and Crenshaw at the end of March, this bipartisan act would:
- Require an assessment and update of the National Action Plan for Adverse Drug Event Prevention;
- Create a healthcare provider educational campaign on preventing adverse drug events, in part by using evidence-based PGx information.
- Incentivize updates to electronic health record systems to ensure that healthcare providers are alerted to interactions between medications and genes when making prescribing decisions;
- Enhance reporting systems that would assist with the reporting of PGx-associated adverse drug events
- A second associated bill authorizes sustained funding for PGx implementation research and guideline development.
- Pharmacy and Medically Underserved Areas Enhancement Act – The bill would enable pharmacists to deliver Medicare Part B services that are already authorized by their respective state laws. Learn more at ASHP.
The Hippocratic oath of “first do no harm” can’t stop with direct patient care; the healthcare industry and its key stakeholders must address persistent public health problems systematically. We have the tools to reduce medication harm by half or more; it is long past time to make this a public health priority. Common-sense legislation needs to be passed to ensure we move beyond an outdated system for medication management and safety that is no longer serving providers or the patients they care for.
Editor’s note: The author on the PGx committee of the NIH Inter-Society Coordinating Committee for Practitioner Education in Genomics (ISCC-PEG), a member of the PGx workgroup for the American Cancer Society Cancer Action Network (ACS CAN) and serves on the steering committee for STRIPE, the FDA collaborative community for PGx.
Photo: z_wei, Getty Images
Kristine Ashcraft has worked in pharmacogenomics since 2000 and was named one of the 25 leading global voices in precision medicine. She is the Founder and President of YouScript (an Aranscia Company), an award-winning clinical decision support tool that has integrated PGx-guided personalized prescribing in the clinical workflow for over a decade. Kristine has 25+ years of experience in various C-level, board, customer success and business development roles. She has authored multiple publications on the clinical and economic benefits of pharmacogenomic testing and serves on numerous PGx advisory groups including the STRIPE Steering Committee, the FDA collaborative community for pharmacogenomics, CPIC, and the American Cancer Society Cancer Action Network PGx task force.
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