How Precision Dosing Technology Helps Prevent Adverse Events

While the eyes of the health care world have understandably been focused on mitigating COVID-19 over the past year, it is important that we remain focused on a critical patient safety issue that can lead to escalating costs and worse outcomes: adverse events (AEs).

Prior to the pandemic, AEs were responsible for 100,000 deaths every year, representing the fourth leading cause of death in the United States. AEs result in an annual increase of approximately $136 billion in the nation’s health care costs, a large percentage of which is avoidable.

The AE problem persists in spite of numerous initiatives, such as an effort by the US Centers for Medicare and Medicaid Services to establish policies, value-based purchasing programs and other financial incentives, to mitigate it.

However, new technology has emerged to help prevent AEs. Precision medicine, and more specifically, precision dosing technology, uses multiple patient-specific factors to individualize medication doses, helping clinicians reduce medication errors that lead to AEs.

Common Factors Driving AEs
One major cause of AEs is a one-size-fits-all approach to drug dosing that is all too common in our health care system. For example, 78% of 181 drugs approved from 2013 to 2017 had only 1 approved dosing regimen, according to a recent study from the FDA.

Further, just 39% included response-guided dosing instructions in the labeling. Contributing to the problem is that many drugs are tested in fewer than 1000 patients, meaning that differences in drug effects are often not thoroughly studied in different patient populations.

Another frequent factor driving AEs is polypharmacy, or the simultaneous use of multiple drugs for treatment. Many current tools, including the Beers criteria for potentially inappropriate medication use in older adults, the Medication Appropriateness Index, and the Screening Tool of Older People’s Prescriptions (STOPP), have not demonstrated the ability to significantly decrease risk.

In other cases, the limitations of the tools available to clinicians at the point-of-care via electronic health record (EHR) systems may lead to AEs. For example, some EHRs’ dose-range-checking alerts are unsophisticated and do not account for individual patient variability in drug response.

Clinician fatigue caused by EHR alerts and pop-ups also contributes to the likelihood of AEs in hospitals. In one notable and regrettable instance a hospitalized teenager was given a 38-fold overdose of an antibiotic, in large part because the ordering physician had been advised by colleagues to "just ignore the alerts" from the EHR.

Model-Informed Precision Dosing to Lessen AEs
Precision dosing technology, called model-informed precision dosing (MIPD) leverages data from existing patients to create and predict another patient’s response to a specific dose of a drug, which greatly aids clinicians in making better dosing decisions. MIPD enables providers to target the optimal dose for individual patients based on unique characteristics, reducing the likelihood of AEs.

MIPD approaches to dosing make real-world patient data more available to clinicians, helping to reduce AEs that result from medications having been tested only in limited populations. MIPD also helps limit alert fatigue for providers because the technology requires active participation from clinicians.

For example, rather than ignoring an alert that pops up in the EHR, with MIPD, clinicians actively assess a patient’s unique pharmacological profile, coupling data specific to the patient with machine learning and pharmacology models that determine the individual patient’s optimal dosing regimen.

MIPD is especially beneficial when used with narrow therapeutic index (NTI) drugs, which are “drugs where small differences in dose or blood concentration may lead to serious therapeutic failures and/or adverse drug reactions that are life-threatening or result in persistent or significant disability or incapacity,” according to the FDA. Many therapeutic areas stand to benefit from precision dosing, including anti-infectives such as vancomycin, immunosuppressants, chemotherapeutics, and biologics.

For example, MIPD has already shown benefits in the treatment of bacterial infections in pediatric patients with vancomycin by lowering the risk of AEs, allowing clinical teams to administer correct doses more quickly and accelerating treatment times. MIPD has also proven effective in dosing of busulfan, a chemotherapy agent for hematopoietic cell transplants, as a study in Frontiers in Pharmacology revealed that using MIPD to personalize busulfan therapy enabled providers to more accurately and precisely reach desired therapeutic ranges for dosing.

New Technology to Solve an Old Problem
Although many of the challenges facing health care, such as AEs, may have received less attention during the COVID-19 pandemic, they didn’t disappear and still require innovative solutions. By using multiple patient-specific factors to individualize medication doses, precision dosing technology holds the potential to enhance patient safety, promote better outcomes and lower health costs.

About the Authors

Michael Neely, MD, is a Professor of Pediatric and Clinical Scholar at the University of Southern California and the Children’s Hospital of Los Angeles (CHLA). He is the director of the Laboratory of Applied Pharmacokinetics and Bioinformatics at the Saban Research Institute, CHLA.

Sirj Goswami, PhD, is CEO and co-founder of InsightRX. Dr. Neely serves on the InsightRX Scientific Advisory Board.