Exam 2 lecture 11

Question 1

genetic info can help:

Answer 1

• develop gene therapy
• predict disease risk
• guide therapy
• guide drug development

Question 2

stake holders involved

Answer 2

patients, healthcare providers, industry, insurers, government, society

Question 3

patient perspective

Answer 3

using it to guide therapy was more widely accepted that predict disease risk

Question 4

provider perspective

Answer 4

using to guide therapy was more widely accepted

Question 5

pharmaceutical industry perspective

Answer 5

mixed incentives

Question 6

positives for pharmaceutical industries

Answer 6

new drug targets
drugs with better side effects
more efficient drug developments
salvage drugs

Question 7

negatives for pharmaceutical industry

Answer 7

decreased market share
fewer blockbuster drugs
orphan popilations

Question 8

diagnostic industry perspective

Answer 8

positive incentive: increased market share

Question 9

insurer perspective

Answer 9

• predicting disease not widely accepted

- guide therapy more accepted (HER2)

Question 10

government perspective

Answer 10

safety and efficacy
medicare/medicaid reimbursement
regulations

Question 11

society perspective

Answer 11

maximize benefits for all stakeholders

minimize risks and costs

Question 12

cost

Answer 12

genetic testing
subsequent intervention
genetic counseling

Question 13

benefits

Answer 13

improved therapeutic response
avoid adverse effects
avoid unnecessary treatments
improved quality of life

Question 14

clinical validity

Answer 14

how consistently and accurately the test detects or predicts the outcomes of interest
how true something is

Question 15

clinical utility

Answer 15

how likely the test is to significantly improve patient outcomes

Question 16

dose limiting toxicity for TMPT polymorphism

Answer 16

myelosuppression (neutropenia)

Question 17

as prevalence goes up

Answer 17

cost effectiveness goes up

Question 18

genotyping prevalence has to be

Answer 18

at least 1% to be cost effective

homozygous TMPT

Question 19

cost effectiveness

Answer 19

<$50.000 per QALY

Question 20

if frequency is 0.5% or less, the cost of the genetic test becomes important & cost effectiveness is retained if

Answer 20

the cost of the genetic test is <$100

Question 21

warfarin

Answer 21

oral anticoagulant for treatment/prevention of thromboembolism

Question 22

dosing algorithm of warfarin

Answer 22

-start at 5 or 10 mg
- check INR day 3
- adjust dose
- check INR day 5
- adjust dose
etc

Question 23

current warfarin challenges

Answer 23

• narrow therapeutic range (INR)
• patients are in therapeutic range only about 66% of the time
• up to 20-fold variability in dose requirements

Question 24

INR too low

Answer 24

ineffective anticoagulation->thromboembolism

Question 25

INR too high

Answer 25

too much anticoagulation->hemorrhage

Question 26

higher dose of warfarin required

Answer 26

- low age, high weight, high Vitamin K intake, smoking, hypothyroidism, CYP2C9 inducers, blacks

Question 27

lower dose of warfarin required

Answer 27

- 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)

Question 28

genetic factors affecting warfarin

Answer 28

- CYP2C9 polymorphism - VKORC1 polymorpism - others (gamma glutamyl carboxylase, CYP4F2

Question 29

CYP2c9 polymorphism with warfarin

Answer 29

- can be impaired a little or a lot | - variants more likely to require lower doses

Question 30

CYP2C9 study results

Answer 30

study group using pharmacogenetic algorithm reached therapeutic & stable INRs sooner than control group

Question 31

VKORC1 polymorphisms

Answer 31

- can cause less warfarin sensitivity, intermediate or more sensitivity -

Question 32

VKORC1 study results

Answer 32

- Primary endpoint not significantly different | - PG algorithm predicted dose better w/ fewer & smaller adjustments but no different in adverse effects

Question 33

precision medicine

Answer 33

an emerging approach for disease prevention & treatment that takes into account people's individual variations in genes, environment & lifestyle

Question 34

the precision medicine initiative

Answer 34

will generate the scientific evidence needed to move the concept into clinical practice

Question 35

research based upon the cohort data will"

Answer 35

- 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