Bacon-wrapped
Pharmacovigilance
with a side of
Genomics
topped with an
Alert Reduction
Optimizing Patient Care and Reducing Alert Fatigue.
FDB Conference
November 5, 2014
Objectives
•
•
•
•
•
•
•
•
Pharmacovigilance – definition and practice
Identify potential ADR’s from the FDB database
Integrating Pharmacovigilance into the workflow - identifying patients at risk
for adverse clinical events
Pharmacogenomic monitoring in MEDITECH
Utilizing FDB resources for Pharmacogenomic data
AlertSpace® overview
Potential Alert reduction as a result of Pharmacovigilance
Outcomes – end user satisfaction, cost savings, optimized care
Bacon-wrapped
Pharmacovigilance
Leveraging MEDITECH’s Pharmacy
application with sophisticated rules to
monitor patient information and prevent
potential adverse clinical events to
medications
Pharmacovigilance
Pharmacovigilance (PV or PhV), also
known as Drug Safety, is the
pharmacological science relating to the
collection, detection, assessment,
monitoring, and prevention of adverse
effects with pharmaceutical products
Pharmacovigilance activities include:
•
•
•
•
•
•
•
Collecting and managing data on the safety of medicines
Looking at the data to detect 'signals' (any new or changing safety issue)
Evaluating the data and making decisions with regard to safety issues
Pro-active risk management to minimise any potential risk associated with
the use of the medicine
Acting to protect public health (including regulatory action)
Communicating with and informing stakeholders and the public
Audit, both of the outcomes of action taken and of the key processes
involved.
First DATA Bank
Data is their Middle Name
Renal Dosage Adjustment
Black Box Warnings
Genomic Data
Drug Disease
……..
Clinical Decision Support
Decision Support focuses on making
the appropriate choices for a therapy
at a given point in time
FDB
Renal Adjustment Data
Pro-active Decision Support
Patients with impaired renal function must
have their drug therapy carefully monitored
to avoid adverse drug events.
– Dose the patient properly
– Monitor the patient for any adverse response
CrCl Rule
(from the archives)
Rule provides the end user with an estimated creatinine
clearance for appropriate patients (site determined age and
CRCL parameters) when entering drugs that may have an
impact on renal compromised patients. The display
includes not only the estimated creatinine clearance but
also all the demographic information utilized in the
calculation and a trend of the serum creatinine levels with
specimen dates and times. Further utilization of the
customer defined screens within the pharmacy module
provides a suggested dose for the medication based on the
calculated creatinine clearance.
MEDITECH
Medication Screen CDS
• PHA DRUG type screen
• Medication Specific Information
• Attached in PHA parameters
• Same for all formulary items
Medication CDS sample – Page 2 (9 pages available)
Page 2 – with data
Clinical Evidence transfer from
Clinician to System
Sample CrCl Order Rule Display
PHA.DRUG CDS
(current)
Global Rules are attached in the Customer Defined
Parameters
Other Medication Rules
Black Box Warning (w/link)
This medication contains a Black Box Warning,
please review additional information uses web
link
Duplicate Generic 2 hr check
This is a more “in your face” duplicate
generic check
Should also be built as POM Rule –
attached to specific medications
eMAR / BMV RULES
• Override setting for particular sites or location with the
use of RULES
• Replace common medication comments related to
administration with rules – i.e. do not exceed amount
of acetaminophen in 24 hours - use rules to total
acetaminophen content and display for user
administering medication when approaching do not
exceed amount – additional rule with BMV could
prevent administration if certain amounts exceeded.
• Prevent administration that could cause a potential
ADE.
Acetaminophen 24 hour rule
Displays cumulative
acetaminophen dose for past 24
hrs once past trigger value
Check Number of Doses and
Levels
This rule displays the number of
doses administered and
previous levels if done.
Black Box Warning (eMAR)
Black Box Warning – POM
Dose Restriction Rule
Uses Drug CDS top control
partial doses of oral forms
Restrict to Specialist MD
Designed to limit ordering of
medication to specific physicians
Pharmacovigilance activities
include:
•
Pro-active risk management to minimise any potential risk associated with
the use of the medicine
Vigilance Survey
• What are you doing now?
• What else should you be doing?
• What will it take to get to the next level?
Vigilance
•
•
•
•
Determine what needs to be “watched”
Establish Surveillance Opportunities
Understand the clinical parameters
Evaluate the system’s ability to capture
and relay data
• Batch vs. Real-time surveillance –(levels
of sophistication)
Opportunities
•
•
•
•
•
Renal Dosing
Antimicrobial Therapy Monitoring
A.D.E. / Black Box Warning Monitoring
Drug Disease Interactions
Pharamcogenomic contraindications
Methodology
• The system contains patient specific
data.
• The Clinician works with specific
triggers of evidence.
• By embedding the triggers into the
system it can provide surveillance to
streamline the clinician processes
Understanding
By leveraging Data with sophisticated
clinical rules and reports to identify
potential drug problems, monitor
laboratory values and alert the
clinician to potential patient
risks. You can reduce potential
adverse events and improve patient
outcomes
Added Sophistication
• Utilizing Rules linked to fields on a
Customer Defined Screen (CDS).
• Activating rules by selecting
appropriate fields on the CDS.
ADE Monitoring
• Medications can be classified on the Drug CDS
as those causing specific ADE’s. Multiple ADE’s
can be associated with a single formulary item.
• A Rule is created for each potential ADE.
• By answering “Y” to the ADE query “Potential
ADE (Y/N)” and associating the appropriate
ADE’s at the “ADE:”the rule will be invoked.
Clinical Evidence transfer from
ADE Monitoring
Clinician to System - Triggers
• Medications can be classified on the Drug CDS
as those causing specific ADE’s. Multiple ADE’s
can be associated with a single formulary item.
• A Rule is created for each potential ADE.
• By answering “Y” to the ADE query “Potential
ADE (Y/N)” and associating the appropriate
ADE’s at the “ADE:” prompt, these refill rules will
be invoked and display on the refill list.
Clinical Evidence transfer from
ADE Monitoring
Clinician to System - Triggers
• Medications can be classified on the Drug CDS
as those causing specific ADE’s. Multiple ADE’s
can be associated with a single formulary item.
• A Rule is created for each potential ADE.
• By answering “Y” to the ADE query “Potential
ADE (Y/N)” and associating the appropriate
ADE’s at the “ADE:” prompt, these refill rules will
be invoked and display on the refill list.
Using a CDS Query to invoke a
Global Rule
By answering “Y” to the ADE
query “Potential ADE (Y/N)” and
associating the appropriate
ADE’s at the “ADE:” prompt,
these refill rules can be invoked
and display on the refill list
Multiple ADE responses
can be entered for a
specific formulary item
Clinical Parameters
(sample triggers)
CDIFF
Positive Stool culture for C.diff
PC<50000
Platelet count less than 50,000
PTT>100
PTT greater than 100 seconds
INR>6
INR greater than 6
Retcount>2
Absolute reticulocyte count greater than
2%
Bili>10
Seum bilirubin greater than 10 mg/dL
ALT>150
Serum ALT > 150 Units/L
IncreaseCR
Increasing Creatinine
IncreaseALT
Increasing ALT(20%)
Hyperkalemia
Serum Potassium greater than 6.5
mmol/L
ADE Monitoring
• Global rules will indicate a potential ADE
and the order that may be causing the
adverse effect.
Sample ADE Rule
; This rule will display patient with cyclosporine > 500 receiving
cyclosporine drug
;
[f rx med]^M,
"PHA.ADEGRP"^GRP,
"CYCLOSPRNE"^CDS,
IF{[f z.get.cds.resp](M,GRP,CDS) ""^RES,
[f rx nth ver Res-RES]("CYCL1",1)^RES,
RES#”1,”^RESDT,RES#”2,”^RESTM,RES#"0,"^RES,
IF{RES>500 "Potential ADE, cyclosporine serum level = "^MSG,
MSG_RES_” on “_RESDT_” @ “_RESTM^MSG,
Q(MSG,RESDT,RESTM);[f rx reject]};
[f rx reject]};
Sample Custom Keyword
z.get.cds.resp
%PHA.RX.zcus.tig.npr.rx.rules.M.get.resp(
; This program will get the ADE group Response from the formulary
Dictionary
; A - Med
; B - Query
; C - Response to check for
;
A^PHA.DRUG.mnemonic,
B^PHA.DRUG.query,
""^PHA.DRUG.query.mult.q^FND,
DO{@Next(PHA.DRUG.query.mult.q)&'FND
IF{@PHA.DRUG.query.mult.resp=C 1^FND}},
FND;
Added Sophistication
An NPR Report printed to the screen that
promotes the ability to provide real-time
intervention on patients when time may be
of the essence.
Real-time Display
Right Arrow for Detail of Order
Order Type CDS
An Additional field can
be added to the order
type CDS. The CDS is
attached in the Order
Type dictionary
Sample Order Type CDS
Once a user puts in a review Date
and Time, the order will drop off
the view board and resets the RX
so that a new reported lab will
trigger it to appear on the board
again if indicated.
Review notes added to note any
changes or notes for that date.
Micro – CS Surveillance
• Displays if patient has been on
antimicrobial therapy greater than x days
(x customer defined)
• Warns if patient is on antibiotic and micro
reports resistance to that antibiotic
• Warns if micro reports positive growth but
patient not on Antibiotic
Querie Responses - Abx
Microbiology Warning
Additional Vigilance
• Change in patient weight > X%
• Warns if patient creatinine clearance
changes by greater than X amount
• Pharmacogenetic Monitoring
–
IN.CYP2C10
• Poor Metabolizer for Plavix.
a side of
Genomics
BACKGROUND
Single Nucleotide Polymorphisms
(SNP’s)
• Human genome contains between 30,000
and 40,000 distinct genes.
• Genetic variation most commonly occurs as
random variations between the nucleotide
sequences of different individuals
• Single base-pair substitutions that occur with
a frequency of greater than or equal to 1% in
a population are referred to as single
nucleotide polymorphisms (SNP’s)
• To date 1.4 million SNP’s have been identified
• More than 60,000 occur in the coding regions of
proteins
• Genes that code for the CYP enzymes 2A6, 2C9,
2C19, 2D6 and 3A4 have shown to be
polymorphic with functional variations on a
significant percentage of ethnic groups.
• The most common and best studied
polymorphisms to date are those that affect drug
pharmacokinetics and pharamcodynamics
Variability in Drug Response
• Pharmacokinetics
– Absorption
– Distribution
– Metabolism
– Excretion
• Pharmacodynamics
– Drug target response
Genomic Discussion Points
• How can Genetic Information impact Clinical Decision Making?
• How can we use EHR’s to bring of Genetic Information into
Standard Practice?
• How can we:
– Minimize side effects
– Reduce adverse drug events and treatment failures
– Improve patient care
• How best can EHR’s Retrieve, Store and Display Genetic
information?
MEDITECH
Focus on Low Hanging Fruit
Better Management of Cardiac Medications: Anticoagulants and
Cytochrome P450 CYP2C19
–
variations in this have a 3.58 times greater risk for major adverse
cardiovascular events such as death, heart attack, and stroke; the
risk was greatest in CYP2C19 poor metabolizers.
New England Journal of Medicine
Better Pain Management : Opiates and P450 CYP2D6
–
–
80% of patients reporting ADRs were shown to have poor CYP2D6
metabolism
Some methadone patients seeking higher doses were Ultra
Metabolizers: proof that they were not exhibiting drug-seeking
behavior
American Academy of Pain Medicine
CYP2D6 - CYP2C19
•
CYP2D6 is involved in the metabolism of:
–
–
–
–
–
–
–
–
–
–
–
•
Codeine (pro-drug)
Prozac
Zoloft
Paxil
Effexor
Hydrocodone
Amitriptyline
Claritin
Cyclobenzaprine
Tagamet
Tamoxifen (pro-drug)
CYP2C19 is associated with the metabolism of:
–
–
–
–
–
–
Carisoprodol
Diazepam
Dilantin
Premarin
Prevacid
Plavix
By analyzing the variation in the two genes, the test predicts whether an individual will
metabolize these drugs more quickly or more slowly than average. These variations can help the
physician identify how a patient's metabolism works. If the test reveals that a patient metabolize
drugs rapidly or slowly, the doctor may consider adjusting your drug dosages or switching to a
non 2D6 or 2C19 metabolized drug. This information can help to maximize the likelihood of
therapeutic effectiveness and minimize the risk of adverse drug reactions.
Breast Cancer Recurrence: Tamoxifen and
Cytochrome P450 2D6
– Recent research has shown that 7-10% of
women with breast cancer may not receive the
full medical benefit from taking tamoxifen due
to their unique genetic make-up. These women
have a version of a gene called Cytochrome
P450 2D6, which reduces the effectiveness of
tamoxifen and increase their chance of breast
cancer recurrence.
Federal Drug Administration
Bringing into Standard Practice Using CPOE ,
Evidence Based Order Sets (EVB) and Clinical
Decision Support:
• EVB Order Set for Cardiac Stent to
include genetic testing for P450 2C19
(CYP2C19)
Clinical Decision Support Rules
• Suggest ordering appropriate Genetic
Screening – if not already on Genetic
Profile (Include reason for testing )
• Review Genetic Profile* and warn user
regarding potential adverse effects (i.e.
Warfarin – bleeding)
• Suggest alternate therapy when
appropriate (i.e. Effient vs Palvix or H2
antagonist vs PPI)
Pharmacogenomic Rules may meet the
“rules” requirement for “Meaningful Use”
New C/S Capabilities
*Incorporation of Problem List with
Pharmacy Conditions will allow Drug
Disease interactions from FDB Data
Warfarin- two genes below
FDB Data
Clopidogrel (Plavix) DNA Test - CYP2C19
Several recent landmark studies have proven the
importance of 2C19 genotyping in treatment using
clopidogrel or Plavix. Researchers have found that
patients with variations in a gene called
cytochrome P-450 2C19 (CYP2C19) have a 3.58
times greater risk for major adverse cardiovascular
events such as death, heart attack, and stroke; the
risk was greatest in CYP2C19 poor metabolizers.
The abstract is available in the online verison of
the New England Journal of Medicine.
Workflow - Stent
1. Patient Identified as a candidate for
cardiac stent.
2. Order Set contains order for screening for
Cytochrome P450 2C19 Genotype test
3. CY2C19*2/*2
4. Patient Id’ d as poor metabolizer – added
to “Problem List”
5. Drug – Disease Interaction displayed
Workflow - Ortho
• Orthopedic EVB Order Sets and Post
Surgical
Pain:
Pre-Op EVB Order Set to include genetic
testing for P450 CYP2D6
 Patients Id ‘d as poor metabolizers will receive warning
when orders for Hydrocodone selected. Switch to
Hydromorphone (Drug –Disease Interaction Display)
Who Should Be Tested
The CYP2C19 test for clopidogrel or Plavix
is considered appropriate for any patient
taking or considering this medication.
REDUCING ADRS AND SAVING MONEY
More than 50% of Americans have gene
based variations that can be tested for and
that increase the risk of an ADR.
The wide use of DNA Drug Sensitivity
Testing has the potential to save tens of
thousands of lives, prevent hundreds of
thousands of serious events that initiate or
extend hospital stays, and save hundreds
of millions of dollars in health care costs.
Fifty-nine percent of drugs most commonly
cited in ADR studies are processed by
enzymes with genes known to have poor
metabolizer variants. This is compared to
7% of a random selection of the top selling
drugs. (JAMA 286:2270 2001).
Currently available tests help predict a
patient's response to many prescription,
OTC (over-the-counter) and herbal
medicines including those used to treat
depression, anxiety, seizures and
psychoses; blood pressure,
anticoagulation and other heart medicines;
anti-diabetic agents, and many pain
relievers.
Many known drug drug interactions are
based on a knowledge of the drug
metabolizing systems that have a high
level of genetic variation. When those
variations are present in individuals taking
more than one drug the chance of having
an adverse drug reaction is greatly
increased.
Hospitalized psychiatric patients who are
poor metabolizers cost $4,000 - $6,000
more in medical care compared to patients
with an average metabolizer genotype.
ALL antidepressants and antipsychotics
are processed by enzymes with a high
incidence of poor metabolizers. Journal of
Clinical Psycopharmacology 20:246 2000
Review – What We Know
• We know that genetic differences can
affect drug response in patients
• We have identified specific SNP’s that
produce specific responses
• We can now identify patients that have
specific Genotypes
• Where do we go from here?
Conclusion
As more patients have genetic profiles performed and
more information is available about medications and
their interactions with different genetic profiles, we will be
able to tailor a regimen with specific medications and
doses for the patient based on the patient’s genetic
make-up. This customization will be in addition to other
commonly acceptable variables used today (age, weight,
sex). The Hippocratic Oath states first do no harm. With
genetic testing, many of the worst side effects from
medications may be more predictable and can prevent
patient deaths from occuring.
topped with an
Alert Reduction
AlertSpace®
Once we have established a robust
surveillance process, we can use alertspace
to filter warnings related to clinically
surveyed parameters.
i.e. If drug A is ordered with drug B there is
an increased risk of drug B reduced renal
function.
If we are continually surveying the renal
function we can notify the physician if this
occurs rather than on order entry.
AlertSpace® Overview - FDB
Questions / Discussion
Bruce Matthias R.Ph., President
The IN Group, Inc.
Bruce.Matthias@theingroup.com