PGx in practice

Question 1

History

Answer 1

-1959: influence of isoniazide blood concentration = term “pharmacogenetics”
-1964: ethanol metabolism genetic variations
-1979: CYP2D6 SNPs

Question 2

Where pharmacogenetics fits into drug therapy

Answer 2

-genetic variations of PK (adme) and PD (receptors/enzymes)

Question 3

Drug labeling

Answer 3

->300 drugs! have PGx labeling
-risks, specific dosing

Question 4

When is PGx most informative?

Answer 4

-drug and event charactericstics
-not taking gene characteristics into consideration

Question 5

Next gen sequencing

Answer 5

-decreasing costs
-inc availability of genetic info
-rn we’re testing for known SNPs
-headed towrds genome wide screening

Question 6

-Omics era

Answer 6

pharmacogenetics = pharmacogenomics = PGx
-focus on smaller effects from multiple variants over whole genome

Question 7

Personalized medicine

Answer 7

-use info about genes, lifestyle, and environment to prevent, dx and tx disease
-in cancer: use tumor infor
-in infection: pathogen info

Question 8

barriers to personalixed med

Answer 8

1. drug approval process
2. traditional clinical practice models (lack of guidelines and proof)
3. translating basivcscience to practice (incorp into guidelines)
4. tech

Question 9

Drug development sycle

Answer 9

-for every 10k leads, only one is approved
-doesnt leave time for biomarker discovery during clinical development
-necessitates early recongition of biomarkers
-trials arent tx people based on genetics

Question 10

Trial design subgroup limitations

Answer 10

-sample sizes would need to inc ($ and time)
-impossible to identify every factor influencing drug response
-trial enrollment harder, maybe unethical if certain subgroup responds poorly

Question 11

Impresion

Answer 11

-1:3 - 1:24 success rate of drug in population

Question 12

precision medicine

Answer 12

-personalized medicine

Question 13

Basket trials

Answer 13

-match pt with rare mutation REGARDLESS OF TUMOR HISTOLOGY to a drug expected to work on mutation
-mulitple types of cancer, 1 mutation

Question 14

umbrella trials

Answer 14

-investigational drug chosen based on PGx biomarker
-1 cancer, multiple mutations that get dif drug based on mutation

Question 15

Problems in traditional practice

Answer 15

-med teams lack expertise
-physicians and pharmacists cover areas of geneticist/counselor w little resources

Question 16

molecular geneticist

Answer 16

-how output w be interpreted

Question 17

Bioinfo support

Answer 17

-how other variants will be incorporated into decision

Question 18

genetics counselot

Answer 18

-who will answer pt questions regarding genetic profile

Question 19

overcoming practice problems

Answer 19

-innovative practice model

Question 20

Sources for PGx guidance

Answer 20

-drug label
-clinical guidelines
-primary lit
-clinical pgx implementation consortium (CPIC)

Question 21

clinical pgx implementation consortium (CPIC)

Answer 21

-guidelines to help clinicians understand how available genetic tests should be used to optimize drug tx
-pharmkgb

Question 22

partial solution to tech outpacing clinical practice

Answer 22

-clinical decision support systems

Question 23

Advance made for implementation of precision med

Answer 23

-enhanced preclinical biomarker screening
-novel trial designs
-innovative prac models
-clinical decision support
-clinical guidelines toward precision med

Question 24

First gen of products towrd precision med

Answer 24

-targeted therapies based on genome wide screening
-personalized immunotherapy