Innovative Approaches to Tackle Polypharmacy Challenges at Point-of-Care

by David Jacobs and Kenneth Ramos

Introduction

First do no harm … this wisdom from the past echo’s loudly today as we concern ourselves with patient safety and adverse drug reactions (ADRs) among the elderly. These areas of clinical practice represent major causes of death, exceeding many of the better recognized causes of mortality. While medicines can have life-altering benefits, a more precise way of selecting and prescribing medications  continues to lag behind other advances in current practice. To this end, we will make the case for a precision medicine approach based on dedicated medical management teams aided by a shared display tool powered by algorithms and underlying integrated data sets. We cite statistics that show how pressing this need has become to treat aging populations on multiple medications (polypharmacy).

The Era of Polypharmacy

Precision medicine approaches remind us that one size does not fit all. A person’s drug response can vary by way of drug–drug and drug–food interactions, gender, age, and disease states. Large interpersonal variabilities of up to 1000-fold exist in response to the same dose of medication.¹ Genetic polymorphisms can define pharmacodynamic and pharmacokinetic profiles, yet this knowledge is not consistently incorporated into standard of care.

How might the provision of precision care better hit the bullseye in the management  of chronic diseases, especially as it relates to polypharmacy? Conventionally, polypharmacy refers to taking five or more medications concurrently. An estimated 15 million patients 65 or older (total population 49 million) have been identified as facing a polypharmacy challenge. Polypharmacy patients often have at least two comorbid chronic diseases, and nearly 50% of older adults are using at least one medication that is not necessary.^2,3 Hospitalized patients average five to eight medications and the number surpasses nine in 40% of nursing home residents. In an increasing number of extreme cases, polypharmacy can approximate 20 drugs posing risks for major adverse drug outcomes. The more medications on board, the higher the risk to patient safety and compromised clinical outcomes.

This growing polypharmacy crisis in the United States especially impacts older individuals often with diminished hepatic and renal functions that place them at increased  risk of ADR-related hospitalizations. A major reason for the crisis is the prevalence of hepatic

“To this end, we will make the case for a precision medicine approach based on dedicated medical management teams aided by a shared display tool powered by algorithms and underlying integrated data sets. We cite statistics that show how pressing this need has become to treat aging populations on multiple medications (polypharmacy).”

cytochrome enzyme mediated drug-drug interactions, a cause which has been estimated to be as high as 80% of the population,² with elder adults known to be at higher risk of adverse effects. Polypharmacy is associated with decreased medication adherence, urinary incontinence, reduced activities of daily living, and loss of physical and cognitive functions. Increased falls occur along with accompanying morbidity and mortality.^4,5 Approximately one in twenty polypharmacy outpatients seek medical care for ADRs,⁴ resulting in health care expenditures increasing by 30%.⁶

“This growing polypharmacy crisis in the United States especially impacts older individuals often with diminished hepatic and renal functions that place them at increased risk of ADR-related hospitalizations.”

Interoperability among electronic health record systems  continue to fall short imposing a clear limitation in the provision of care and the refinement of medical services. The burden of polypharmacy and medication reconciliation often negatively impact primary care clinicians who may not have sufficient data at point-of-care. Primary care clinicians thus face a major polypharmacy challenge due to the combined failures of integration of electronic health records from different providers and the absence of a central “clearing house” that can reconcile medication orders and use.

Steps to Address the Challenge

Can we identify options compatible with current clinical workflows to address these challenges? As a first step, we posit that the creation of interdisciplinary precision management clinics can help deploy innovative strategies to tackle polypharmacy challenges. We propose one of the primary metrics in such settings should be the reductions polypharmacy challenges determined systematically by tracking incremental changes in clinical outcomes following medication adjustments.

Key to a strategic long-term solution is a medical management team approach that capitalizes on the contributions of case coordinators, nurses, pharmacists, physicians, and others – all who can engage patients in and out of the clinical setting and garner meaningful information such as phenotypic, functional, and social determinants of disease. These data can be collected as computable actionable data  prior to a visit so that what happens between visits is readily integrated with data collected at the visit for better optimization of medical care and communication between providers and patients.

Tools that can support the activities of the medical management team could include an online dashboard that draws the attention of providers and patients to identify those at heightened risk of ADRs. The dashboard would include data on medication reconciliation, medication and treatment adherence, pharmacogenomics and pharmacokinetics data (as appropriate), and other relevant modifier data that can impact medication use, safety, and efficacy. The dashboard should be developed as a patient-centric clinical tool for optimization of care and subject to scheduled cycles of validation and optimization.

Data collected and integrated into the dashboard would be selected to answer important questions related to the adoption of precision approaches into primary care and the management of issues such as non-adherence versus drug metabolism, optimization of workflows, and recognition of overloaded metabolic pathways in polypharmacy cases.

The utility of the proposed approach is exemplified in the psychotropic  domain,⁷ where initiation of standard dosing regimens with commonly prescribed antidepressants is followed by lengthy trial and error regimens before the desirable clinical response can be achieved. In a modified precision management scenario, the provider would know from the outset if the patient is an ultra-rapid or a slow metabolizer for the CYP enzymatic pathway in question and use this knowledge to more readily identify the drug of choice. If the clinical dashboard identifies a patient that is receiving several medications competing for a common pathway, proper adjustments can be made proactively to avoid ADR. As more data are entered, the clinical decision support tools can continue to be refined.

We submit that implementation of a precision approach can help to accommodate clinical work flows currently in practice. The intervention can be implemented in a conventional clinic setting, as well as using telehealth services and virtual tools. The latter approach is particularly attractive as providers continue to grapple with the impact of the SARS-CoV-2 pandemic. In fact, the distribution of services, data capture and analysis using electronic technologies can facilitate long-distance,  patient-clinician  interactions and the delivery of inter-disciplinary education, intervention and monitoring. Remote delivery of a pharmacogenomic service is advantageous in rural settings where access to specialized services can be limited. The overall approach will build on the activation of a dedicated management team aided by computer-based algorithms that integrate multiple data sets contributing to fewer ADR’s, better treatment regiments, reduced costs, and making medicine more preci.

Kenneth S. Ramos, M.D., Ph.D., is the Alkek Chair of Medical Genetics at Texas A&M University Institute of Biosciences and Technology. He also serves as Assistant Vice Chancellor for Health Services and Associate Vice President for Texas A&M Health. A member of the National Academy of Medicine, Dr. Ramos has worked closely with colleagues throughout the world to steer the changing landscape of medicine and healthcare and provide academic, executive, administrative, and scientific leadership in the areas of genomic and precision medicine. Translational research in his laboratory focuses on repetitive genetic elements, while his clinical investigations focus on the development and characterization of diagnostic and prognostic biomarkers of cancer and pulmonary disease and pharmacogenomics.

David Jacobs. M.D. is Chief Medical Information Officer for Goldblatt Systems, a health science company in Arizona that focuses on using a clinical semantic network with electronic health records and laboratory-based data focused on pharmacogenomics. He has been with the company since 2016 involved in the development and execution of a polypharmacy solution at the point of service for clinicians. Prior to that Dr. Jacobs practiced medicine in the areas of in-patient post-acute care and outpatient interventional pain management. During his tenure as medical director of an acute inpatient rehabilitation hospital, Jacobs became acutely aware and interested in the challenge of polypharmacy to the senior rehabilitation population and its impact on their functional outcomes, where he developed system-wide approaches to this issue prior to having tools and technology, such as electronic decision support or pharmacogenomic testing.

References

1. Genetic variability in susceptibility and response to toxicants, Magnus Ingelman-Sundberg Toxicology Letters, 120 (March 2001) 259-268
2. The challenge of managing drug interactions in elderly people, Louise Mallet, Anne Spinewine, Allen Huang, The Lancet, July 14, 2007, DOI:https://doi.org/10.1016/S0140-6736(07)61092-7
3. Clinical consequences of polypharmacy in elderly, Hanlon J, Hajjar Expert Opin Drug Safety. 2014 Jan; 13(1): 10.1517/14740338.2013.827660. Maher RL , Hanlon J, Hajjar ER. Expert Opin Drug Safety. 2014 Jan; 13(1): 10.1517/14740338.2013.827660.
4. Adverse drug events in the outpatient setting: an 11-year national analysis, Bourgeois FT, Shannon MW, Valim C, Mandl KD Pharmacoepidemiol Drug 2010 Sep; 19(9):901-10
5. Fall-risk screening test: a prospective study on predictors for falls in community-dwelling elderly, Tromp AM, Pluijm SM, Smit JH, Deeg DJ, Bouter LM, Lips P J Clin 2001 Aug; 54(8):837-44.
6. Potentially inappropriate medication use in elderly Japanese patients, Akazawa M, Imai H, Igarashi A, Tsutani Am J Geriatr Pharmacother. 2010 Apr; 8(2):146-60
7. Antidepressant prescribing in the precision medicine era: a prescriber’s primer on pharmacogenetic tools, Chad Bousman, Malcolm Forbes, Mahesh Jayaram, Harris Eyre Charles F. Reynolds,Michael Berk, Malcolm Hopwood, and Chee Ng. BMC Psychiatry. 2017; 17: 60.

Author Contributions:

All authors made substantial contributions to the conception and design of the work and participated in drafting and revising it critically for important intellectual content. All authors approved of the final version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Conflict of Interest:

Author David Jacobs is employed by the company Goldblatt Medical System. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.