Pharmacogenomics to Increase the Effectiveness and Safety of Drug Treatments

Reducing Health Care Costs With Pharmacogenomics: The Teacher’s Retirement System of Kentucky (TRSKY) Story

When we are sick, we seek relief as quickly as possible. Fortunately, medical science has developed an extensive pharmacopeia for treating a very large number of pathologies. Although popping a pill, drinking an elixir, or getting an injection often provides relief or a cure, these solutions can come with side effects. One of the side effects that has the highest impact on the patient and healthcare costs is when a drug produces an unwanted effect or injury – also known as an adverse drug event (ADE). ADEs can range from unexpected side effects to life-threatening reactions. In fact, according to the US Health and Human Services (HHS) Office of Disease Prevention and Health Promotion (1), annually, adverse drug effects can:

Account for an estimated 1 in 3 of all hospital adverse events
Affect about 2 million hospital stays each year
Prolong hospital stays by 1.7 to 4.6 days
Account for over 3.5 million physician office visits
Result in an estimated 1 million emergency department visits
Drive approximately 125,000 hospital admissions

In addition to causing additional discomfort and stress for those affected, these obviously drive up health care costs.

Genotypes, Drug Metabolizing Enzymes (DMEs) and Drug Effectiveness

A less obvious problem is that the response to a medicine often depends on the genotype of the recipient. Most modern drugs are acted on by drug metabolizing enzymes (DMEs). Enzymes that fall into this group are required to clear the drug from the system or are required to convert a precursor molecule into a biologically active molecule. However, not all individuals are equipped with the same set of DMEs. Some individuals may completely lack functional copies of the enzymes needed to convert a drug precursor into the biologically active molecule, rendering the treatment ineffective. Some individuals may have enzymes with lower functional activity, meaning the precursor molecule is converted to functional drug at a lower rate, effectively lowering the dose of the treatment. Alternatively, individuals might have lower activity of the enzymes that degrade a drug, resulting in higher circulating concentrations of the biologically active molecule. Some individuals may convert a drug into a toxic product as a result of their inborn metabolism and others might be more sensitive to its side effects.

Pharmacogenomics – Analyzing the Link Between DME Genotypes and Drug Metabolism

Pharmacogenomics is the field that analyzes the link between DME genotypes and drug metabolism. There is increasing interest among patients, medical practitioners, governmental health services and insurance providers to use pharmacogenomics to increase the effectiveness and safety of drug treatments. Finding the most effective, safe and economical treatment options involves making sure the recipient’s genotype can metabolize the drug as intended.

Using Pharmacogenomics to Optimize Administration of Medication

Seeking Effective Treatments and Reducing Costs

Although modern medicines can be highly effective, they can also be expensive. In the US alone, spending on pharmaceutical treatments is around $350 billion annually (2). In the current climate of finding ways to decrease healthcare costs, it is therefore important to rapidly determine the treatment and dosage that treats the pathology most effectively. Recently, in an effort to reduce medical costs and provide a greater return on investment, a pilot program was initiated by the Teacher’s Retirement System of Kentucky (TRSKY). The TRSKY is a pension fund serving 34,000 retirees, ranging in age from 65-107. Seventy-five percent of members had high blood pressure or heart disease, 58% had high cholesterol, 50% had pain or inflammation, and they took an average of 15 prescriptions to help alleviate these and other conditions. However, it was not clear that the prescription regimens that the members were on were safe, necessary, or that they would even work. Answering these questions could improve outcomes for the individuals, and by reducing unnecessary doctor/hospital visits, reduce the overall costs for the fund.

Teacher’s Retirement System of Kentucky (TRSKY) Pilot Program

Geneticists, Doctors, and Pharmacists Working Together

To focus on improving medication safety and efficacy for its members, TRSKY collaborated with Coriell Life Sciences to utilize genetic testing and personalized therapy analysis delivered to physicians through expert pharmacist consultation. The study began by collecting more detailed medical information on about 5900 members who participated in the study. Initial analysis found that cutting potential misdirected medical spending on medications could potentially save over $16 million dollars. This increased efficiency included identifying patients taking the wrong dose, determining which patients should stop a medication, and notifying patients for which better alternatives were available.

The second step was to collect genomic samples from the participants. Coriell Life Sciences sent out an at-home collection kit and extracted the genomic DNA from the returned kits at their laboratories. They then analyzed the genomic sequences, with particular attention paid to DME allele configurations and other pharmaceutically important loci. Once the results were generated, members then met with geneticists, doctors and pharmacists to explain the report and communicated to the individual members the medication action plan.

Lower Hospitalizations, Reduced Hospital Admissions, Reduced Spending on Medications

Success was measured several ways. The study found that 57% of the participants could have their medical dose optimized, 33% had better alternative medicines, and 10% should stop taking one of their prescriptions entirely. Another metric was to track a factor called MA3: a measure of medication adherence, medication appropriateness, and medication adversity. After delivery of the Medication Action Plans, there was a 28% reduction in MA3-related risk incidents. Fiscally, there was a 17% reduction in cost-to-plan spending after 6 months, compared to a 2.5% increase in those who did not participate in the study. Finally, those who took actions based on their personalized medication action plan reported much improved performance efficacy of the drugs that were prescribed for them.

Based on these results, the insurance underwriter for the TRSKY fund calculated that if they tested every member, they could expect a $21.7 million reduction in annual health care costs. Satisfaction with the results of the pilot study was indeed universal.

Benefits of Preemptive Pharmacogenomics

Knowing DME Genotypes Can Increase Medication Efficacy and Safety, Decrease Discomfort and Reduce Cost

This example shows the value of preemptive pharmacogenomics for controlling health care costs. In short, by knowing the patient’s DME genotypes, the appropriate drug, correct dose, and biologically active version can be matched to the individual. In many cases, this information will increase efficacy, increase safety, decrease discomfort, and reduce costs. Pharmacogenomics therefore has enormous potential to improve the healthcare system for all participants.

References

https://health.gov/our-work/health-care-quality/adverse-drug-events#ref1
Rajkumar, SV. The high cost of prescription drugs: causes and solutions. Blood Cancer J. 10(6): 71 (2020). doi: 10.1038/s41408-020-0338-x