Description

Background and Rationale Medication prescribing is one of the most common medical interventions. In the U.S., 81% of adults report taking at least one medication in the past week, and 50% take prescription medications. Among older adults, 39% meet the criteria for polypharmacy, defined as the use of five or more chronic medications.

Polypharmacy is strongly associated with adverse drug events (ADEs). Each day, approximately 750 older adults in the U.S. are hospitalized due to ADEs, with half of these patients taking five or more medications. Nearly 60% of older adults are prescribed at least one potentially unnecessary medication.

Traditional prescribing often follows a "one-size-fits-all" approach, which does not account for genetic differences in how individuals metabolize drugs. These genetic variations can lead to ineffective treatment or harmful side effects. Pharmacogenomic-guided prescribing may provide a safer, more personalized approach by identifying drug-gene interactions and tailoring medication choices.

Falls and Medication Safety Falls are one of the most serious and preventable ADEs among older adults. Falls are the leading cause of injury-related morbidity and mortality in older populations, with over 700,000 hospital falls in the U.S. annually. Polypharmacy, especially the use of fall-risk-increasing drugs (FRIDs), contributes substantially to this problem.

By integrating pharmacogenomic testing into medication management, clinicians may be able to reduce fall-related ADEs and improve overall prescribing safety.

Study Objectives and Aims The Geriatric Emergency Department Pharmacologic Harm Prevention Project (The GREAT PHARM) seeks to evaluate whether pharmacogenomic-guided prescribing can reduce ADEs and falls among older adults.

Aim 1: Compare the incidence of recurrent falls, ADE-related emergency department (ED) visits, and all-cause mortality in patients receiving pharmacogenomic-guided medication optimization versus usual care.

Secondary Aim 1: Assess barriers to implementing pharmacogenomic-based prescribing. Aim 2: Determine the prevalence of harmful gene-drug interactions and abnormal drug levels in older adults presenting to the ED after a fall.

Aim 3: Compare self-reported wellbeing and health satisfaction between patients who receive pharmacogenomic-guided prescribing and those receiving usual care.

Study Design

• This is a randomized clinical trial enrolling approximately 1,000 participants aged 65 and older.
• Eligibility: Adults ≥65 years presenting to the ED with a ground-level fall.
• Exclusion criteria: Hospice care or Do Not Resuscitate (DNR) status.

Randomization: Participants will be randomized (via REDCap) into two study arms:

1. Control Group (Current Care) - Standard prescribing practices; pharmacogenomic results provided to primary care physicians only after study completion.
2. Intervention Group (Pharmacogenomic-Guided Prescribing) - Standard care plus pharmacogenomic results provided to the primary care physician during the study for medication optimization.

Interventions

All participants will:

• Provide a one-time cheek swab sample for DNA analysis (testing 26 metabolic enzyme systems).
• If blood is drawn for routine ED care, provide an additional small blood sample (\~5cc) for drug-level analysis. Blood concentrations will be assessed using mass spectrometry at the Florida Atlantic University Bioanalytical Core Facility.
• Complete a monthly calendar to record medication changes, falls, and fall-related injuries.
• Participate in monthly follow-up phone calls (for 6-7 months) to track falls, side effects, and overall health.
• Authorize access to primary care physician medical records for up to one year to confirm study outcomes.

Outcome Measures

Primary Outcomes:

1. Incidence of recurrent falls during 6-7 months of follow-up.
2. Incidence of ADE-related ED visits.
3. All-cause mortality.

Secondary Outcomes:

1. Prevalence of harmful gene-drug interactions in older adults presenting with falls.
2. Prevalence of abnormal drug levels in patients with pharmacogenomic variations.
3. Patient-reported wellbeing and health satisfaction.
4. Barriers to implementation of pharmacogenomic-guided prescribing.

Duration of Participation Each participant will be followed for approximately 6-7 months, with ongoing monitoring through phone calls, calendars, and medical record review.

Significance This trial will evaluate whether personalized prescribing guided by DNA testing can reduce medication-related harm, prevent recurrent falls, and improve overall quality of life for older adults. If successful, the study will provide strong evidence for integrating pharmacogenomic-guided prescribing into standard clinical care for geriatric patients at risk of medication-related harm.