Exam 2 lecture 11 Flashcards
genetic info can help:
- develop gene therapy
- predict disease risk
- guide therapy
- guide drug development
stake holders involved
patients, healthcare providers, industry, insurers, government, society
patient perspective
using it to guide therapy was more widely accepted that predict disease risk
provider perspective
using to guide therapy was more widely accepted
pharmaceutical industry perspective
mixed incentives
positives for pharmaceutical industries
new drug targets
drugs with better side effects
more efficient drug developments
salvage drugs
negatives for pharmaceutical industry
decreased market share
fewer blockbuster drugs
orphan popilations
diagnostic industry perspective
positive incentive: increased market share
insurer perspective
- predicting disease not widely accepted
- guide therapy more accepted (HER2)
government perspective
safety and efficacy
medicare/medicaid reimbursement
regulations
society perspective
maximize benefits for all stakeholders
minimize risks and costs
cost
genetic testing
subsequent intervention
genetic counseling
benefits
improved therapeutic response
avoid adverse effects
avoid unnecessary treatments
improved quality of life
clinical validity
how consistently and accurately the test detects or predicts the outcomes of interest
how true something is
clinical utility
how likely the test is to significantly improve patient outcomes
dose limiting toxicity for TMPT polymorphism
myelosuppression (neutropenia)
as prevalence goes up
cost effectiveness goes up
genotyping prevalence has to be
at least 1% to be cost effective
homozygous TMPT
cost effectiveness
<$50.000 per QALY
if frequency is 0.5% or less, the cost of the genetic test becomes important & cost effectiveness is retained if
the cost of the genetic test is <$100
warfarin
oral anticoagulant for treatment/prevention of thromboembolism
dosing algorithm of warfarin
-start at 5 or 10 mg
- check INR day 3
- adjust dose
- check INR day 5
- adjust dose
etc
current warfarin challenges
- narrow therapeutic range (INR)
- patients are in therapeutic range only about 66% of the time
- up to 20-fold variability in dose requirements
INR too low
ineffective anticoagulation->thromboembolism
INR too high
too much anticoagulation->hemorrhage
higher dose of warfarin required
- low age, high weight, high Vitamin K intake, smoking, hypothyroidism, CYP2C9 inducers, blacks
lower dose of warfarin required
- high age, low weigh, low vitamin K intake, cancer, liver disease heart disease, hyperthyroidism, factor VII or X mutation, female, drugs (amiodarone, statins, azoles, sulfa)
genetic factors affecting warfarin
- CYP2C9 polymorphism
- VKORC1 polymorpism
- others (gamma glutamyl carboxylase, CYP4F2
CYP2c9 polymorphism with warfarin
- can be impaired a little or a lot
- variants more likely to require lower doses
CYP2C9 study results
study group using pharmacogenetic algorithm reached therapeutic & stable INRs sooner than control group
VKORC1 polymorphisms
- ## can cause less warfarin sensitivity, intermediate or more sensitivity
VKORC1 study results
- Primary endpoint not significantly different
- PG algorithm predicted dose better w/ fewer & smaller adjustments but no different in adverse effects
precision medicine
an emerging approach for disease prevention & treatment that takes into account people’s individual variations in genes, environment & lifestyle
the precision medicine initiative
will generate the scientific evidence needed to move the concept into clinical practice
research based upon the cohort data will”
- advance PG, the right drug for the right patient at the right dose
- ID new targets for treatment & prevention
- test whether mobile devices can encourage healthy behavior
- lay scientific foundation for precision medicine for many diseases
