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Adverse Drug Event
Risk Management Program
Today’s Presenter
Robert Rupard CEO & Founder
https://www.linkedin.com/in/robertrupard
404-729-1450
Who Are We?
An Innovative Partnership
“At PharMerica, we recognize the value of using innovative medical
technologies to drive better outcomes for our customers and their
residents. Deploying genetic testing programs in the highest risk
resident populations will ultimately lead to reducing risk of negative
outcomes and potentially lower cost. The differentiator for both
PharMerica and Pro-GeneX is our unique approach in leveraging data
to improve efficiencies for our facilities and utilizing electronic results in
our pharmacy systems and operations.”
Sonja Quale, Pharm.D.
Vice President and Chief Clinical Officer
PharMerica
Who Are We?
Pro-GeneX is a company focused on reducing Adverse Drug Events in
Long Term Care. We work closely with PharMerica to reduce adverse
events, eliminate medications that are unnecessary or ineffective,
control costs, and improve the overall quality of life for residents in our
mutual client facilities.
For millions of years mankind lived just like the animals.
Then something happened that unleashed the power of our imagination…
We learned to talk.
There's a silence surrounding me
I can't seem to think straight
I'll sit in the corner
No one can bother me
Where do we go from here?
It doesn't have to be like this..
All we need to do is make sure we keep talking
David Gilmour
Pink Floyd
The Current Clinical Paradigm
More often than not…Everyone is working in a bubble
THE LTC CARE TEAM
How to facilitate
better
communication?
Be Relevant
What Keeps You Up at Night?
• Maintaining Census
• Reducing Readmissions
• Reducing Falls
• Achieving Better Outcomes
• Lowering Costs
• Meeting CMS Mandates
ADVERSE EVENTS
This Year’s Big Problem
Adverse Events
• A 2014 Office of the Inspector General (OIG) report, "Adverse Events in
Skilled Nursing Facilities: National Incidence Among Medicare
Beneficiaries," found that 1/3 of skilled nursing facility residents were
harmed by adverse or temporary-harm events within the first 35 days of a
stay, and that 37% of these adverse events were medication-related.
• The 2nd most frequent cause of medication-related adverse events
was excessive bleeding related to anticoagulant use.
• Recognizing the necessity of anticoagulant therapy for many resident
conditions, CMS is focusing on the need for effective monitoring systems
to ensure safe administration and positive outcomes.
CMS-Adverse Drug Events
You Need A
System!
What do we know?
• 37% of injuries to residents in LTC have a
medication component
• 65% of medications that cause these
things have a genetic component
• ALL focus point medications have a
genetic component: Antipsychotics,
Antidepressants, Opioids, Anticoagulants,
Benzodiazepines.
Simple Genetic Evaluation
• Helps understand both pharmacokinetic
and pharmacodynamic functions on an
individual basis
• Identifies risks
• Pinpoints efficacy potential
• Helps in attaining maximum therapy in
less time than current methods
• Is not a full genome map
• Paid for by Medicare/Medicaid
Why is Pharmacogenomics Important?
73%
55%
50%
40%
36%
30%
0% 10% 20% 30% 40% 50% 60% 70% 80%
Oncology
ADHD
Hypertension
Pain
Depression
Cardiology
Patient Population, Ineffective Drug
Polypharmacy
DDI 66%
DGI 15%
DDGI 19%
SIGNIFICANT INTERACTION RISK High risk of adverse drug
events (ADEs) as a result of:
• Drug-Drug Interactions (DDIs)
• Drug-Gene Interactions (DGIs)
• Drug-Drug-Gene Interactions
(DDGIs)
Polypharmacy is the simultaneous use of multiple drugs by a
single patient, for one or more conditions.
Enzyme expression (quantity) in the body is coded for by individual genetics and categorized in 4 ways:
• Extensive Metabolizer: This is a normal level of enzyme production or expression
• Intermediate Metabolizer: This is a less-than-normal level of enzyme expression
• Poor Metabolizer: This is a very low level of enzyme expression
• Ultra-rapid Metabolizer: This is a very high level of enzyme expression
The Science of
Pharmacogenetics
Scenarios
1. The Poor Metabolizer - a patient takes medication in the morning but the gene that metabolizes that drug does not clear out the medication before the next dose. Doses 'pile up' on each other becoming toxic and creating increased side effects. This can cause an Adverse Drug Event. 2. The Ultra-Rapid Metabolizer - a patient takes blood pressure medication in the morning but the phenotype of the gene that metabolizes it is Ultra-Rapid, creating lots of extra metabolizing enzymes, thereby ’clearing out' the medication by noon. That patient may not experience a constant level of medication therapy. In some cases, the medication won’t work at all. Solution: Based upon the Pharmacogenetic profile, change to different substrates, dosage or frequency.
Prodrug Scenarios Prodrugs are more complex; they require the presence of one enzyme to convert it to an active form and other enzymes to clear out the medication from the system over time. Examples: Codeine & Plavix. 1. The Poor Metabolizer – Lower levels of conversion enzyme results in poorer-than-expected therapeutic benefit. 2. The Ultra-Rapid Metabolizer – High levels of conversion enzymes result in greater than anticipated plasma levels of medication. Depending on the drug, this could be very dangerous resulting in overdoses, high levels of side effects adverse drug events and even death. Solution: Based upon the Pharmacogenetic profile, change to different substrates, dosage or frequency.
Gene Relevance Table • CYP450 - CYP1A2, CYP2B6, CYP3A4, CYP3A5
• CYP2C19 – Plavix Focus
• CYP2C9 - Warfarin Sensitivity
• CYP2D6 – Codeine Conversion
• Risk Factors: MTHFR, Hyperlipidemia, Factors II and V
• ABCB1- ABC Transporter Resistance; Multidrug resistance, Inflammatory Bowel
Disease
• ADRA2A -ADHD; Clozapine-induced sialorrhea (CIS)
• ANKK1/DRD2 - Addictive Behaviors, Dopamine Receptor; Dissociative Personality
Disorder, Schizoid/Avoidance Behavior
• APO E - Hyperlipidemia/AVD
• COMT - Intersynaptic Serotonin Metabolizer
• OPRK1 - Opioid Receptor; Pain
• SLC6A4 - Serotonin Transporter Expression
• SLCO1B1 - Statin Toxicity; Simvastatin Sensitivity
• SULT4A1 - Neurotransmitter Metabolism; Susceptibility to Schizoid Symptoms
• UGT2B15 - Estrogen and Androgen modulation; cancer drugs
• VKORC1 - Warfarin Sensitivity
Serotonin Function
COMT and
SLC6A4
Remove
Serotonin
Serotonin Transporter Expression
Of the 27 patients* tested:
• 4% have normal expression of the serotonin transporter SLC6A4,
• 44% have low expressions of the serotonin transporter and
• 52% had a decreased level of serotonin transporter.
Takeaway: Serotonin, the ‘feel good’ chemical, is not being recycled which contributes to increased use of costly anti-psychotics.
Typical Population Results
This group
has the highest fall risk
Poor Transporter Function + SSRI = High Serotonin Levels
SSx of Excess Serotonin:
• Agitation
• Dilated Pupils
• Dizziness
• Fatigue
• Headache
• High Blood Pressure
• Mania/Hypomania
• Rapid Heart Rate/Tachycardia
• Restlessness
• Weight Gain
These contribute to pharmacy cascade.
The Problem with Too Much Serotonin
This group
has the highest risk for
elevated Seretonin
Hey… Wanta Buy A Test?
• Volume Driven
• Minimal Education
• Minimal Support
• Kickback Schemes
THE CULPRITS RESPONSIBLE FOR A BAD NAME
Slope of Enlightenment : Product
Development and Enhancement
Visibility
Time
Innovators Early
Adopters
Early Late
Majority
Laggards
Typical Adoption Curve
Peak of Inflated
Expectations :
“Magic Bullet”
Normal Adoption
Bell Curve
Proper Product Application:
Pro-GeneX & PharMerica
As Reimbursements Fall
Adoption Rises with
Outcomes
Reimbursements
Disillusionment Trough
PGX Misconceptions & Truths
Misconception:
Pharmacogenetics is about changing medications….
– Limits adoption
– Minimizes benefit
Truth:
Pharmacogenetics is a powerful risk management tool for clinicians and facilities operators.
The Messaging Problem
Alter the message from: “change
medications” to:
Properly manage potential problems related
to high-risk and problem-prone medications,
using no-cost real-time surveillance of
medication prescribing.
Elements of System Success
Risk Awareness
Risk Education
Clinical Team Interaction
Documentation of Actions
Continuous Monitoring
Where are my biggest risks?
What is my highest risk subgroup?
Clinicians, Pharmacist, Pro-Genex
Demonstration of Existence of ADE Intervention System
Game-changing, Weekly ADE Surveillance
Risk Awareness and Education
Risk Awareness:
Risk Education
Identify ADE High Risk Residents the Way that CMS and
Surveyors Do; Evaluate by Pharmacy
Identify Subgroups with Genetically Enhanced or
Exacerbated Risk for Maximum Efficiency of Staff
Interventional and Pre-emptive Effort
PGx is a key element of Risk Education
Managed vs. Unmanaged Risks
Solving problems requires assignment of numeric metrics
Managed Risks are those that are known
Unmanaged Risks are those that are unknown
Outcomes improvement comes from reacting to known risks
Overall goal is to reduce unmanaged risks by 70% in a mature
program
First pass goal was to reduce unmanaged risks by 30%
An Unmanaged Risk is defined as a resident who is on one or
more high-risk medications and no information as to the genetically-
enhanced adverse drug event risks is available.
Approaching Risk Reduction: Assigning Proper
Metrics
Selecting the Right Individuals for
Maximum Benefit
Overall
Resident
Population
ADE/ADR
High Risk
Group
By
Pharmacy
70%
ADE
High-Risk
Group
By
Pharmacy
With
Genetic
Exacerbation
65%
Opioids
Antidepressants/Antipsychotics
Anticoagulants/Antiplatelets
Benzodiazepines
Anticonvulsants
Bursting the Bubbles!
Test Results
Consultant
Interactions
Client Facility
Clinical Education/Strategies
Outcomes
Improvements
Our Goal: Knowing more about individual medication risks
and communicating them for better prescribing decisions and
enhanced consultant medication change/reduction/elimination
opportunities
Delivering Context to Report Data
Delivering Context to Report Data
Delivering Context to Report Data
Delivering Context to Report Data
The proper use of technology:
• Allows rapid review of data
• Promotes better adoption of information to improve outcomes
• Allows report data to be dynamic
• Enhances current care paradigms to maximize benefits of new information
The Pro-GeneX/PharMerica Interaction
Initial Data for Patient Selection Assistance
Consulting Pharmacist Interactions on Risks
Weekly Data for Evaluation of New Risks
Minimal Facility Staff Time Impact/Maximum Results
Dedicated Nurse Practitioner for Clinical Interactions
The Net Result: Less Bubbles!
Let’s Keep Talking!
