New Approach to Medicine: Personalized Medicine ... · • Pharmacogenetics: the study of variability in drug response due to genetics; relation to genes which determine drug metabolism

New Approach to Medicine: Personalized

Medicine/Pharmacogenetics/Pharmacogenomics

Bojana Stevich-Heemer, MS, PharmD, MEd, BCOP

Associate Professor - LECOM School of Pharmacy

9/22/2019

Required Disclosure

• The presenter for this activity has been required to

disclose all relationships with any proprietary entity

producing health care goods or services, with the

exemption of non-profit or government

organizations and non-health care related

companies.

• No significant financial relationships with

commercial entities were disclosed by any of the

speakers.

1.Pharmacogenetics has potential

to? (Select all that apply)

a. Improve patient outcome

b. Decrease risks of adverse events

c. Promote use of targeted cost-

effective therapy for patient care

2.Genomic medicine can help with which

of the following? (Select all that apply)

a. Disease risk stratification

b. Disease diagnosis

c. Disease prognosis

d. Selecting optimal therapy

e. Disease monitoring

3. Analytic validity is defined as?

a. Accuracy with which a specific

characteristic is identified in the

laboratory test

b. Accuracy with which a genetic test

identifies a specific clinical condition

c. Risk and benefits that result from genetic

test use

4. Which of the following is true about

reactive pharmacogenetic tests?

a. They are ordered when the new medication

is prescribed

b. Obtained for future use when needed in the

clinical setting

c. Also called prospective testing

5. The Genetic Information

Nondiscrimination Act of 2008 protects

from discrimination based on genetic

information in?

a. Health insurance only

b. Employment only

c. Health insurance and employment

d. Neither health insurance nor employment

• At the completion of this activity, the

participants will be able to:

• List indications for use of pharmacogenetics and

pharmacogenomics

• Describe major methods for evaluating evidence

for application of pharmacogenetics and

pharmacogenomics in the clinical practice

• Evaluate strengths of pharmacogenomics data

• Apply pharmacogenomics data for different

disease states

Objectives

Objective: List indications for use of

pharmacogenetics and

pharmacogenomics

• Personalized/precision medicine: right

treatment to the right person at right dose with

maximizing efficacy and minimizing toxicity

• Pharmacogenetics: the study of variability in

drug response due to genetics; relation to

genes which determine drug metabolism

• Pharmacogenomics: broad term which includes

all genes in the genome that may determine

drug response

Personalized Medicine, Pharmacogenetics,

and Pharmacogenomics

• Pharmacogenetics/pharmacogenomics can

target genes that are involved in drug:

• Metabolism

(pharmacokinetic/pharmacodynamics)

• Binding and/or interfering with different

cellular process

Pharmacogenetics/Pharmacogenomics

• Pharmacogenetics uses genetic information to

improve clinical outcomes of pharmacotherapy

• Pharmacogenetics has potential to:

• Improve patient outcomes

• Decrease risks of adverse event

• Promote use of targeted cost-effective therapy

for patient care

Pharmacogenetics in Clinical Settings

Klein ME et. al. Journal of Pharmaceutical Sciences 106. 2017. 2368-2379

• According to the National Human Genome

Research Institute genomic medicine is defined

as:

“Emerging medical discipline that involves

using genomic information about an individual

as part of their clinical care (e.g. for

diagnostic of therapeutic decision-making)

and the health outcomes and policy

implications of that clinical use”

Genomic Medicine

National Human Genome Research Institute at: www.genome.gov/27527652/genomic-medicine-and-health-

care/

• Genomic medicine: individual patient’s genotypic information in his or her clinical care

• Includes both Mendelian and multigenic complexes diseases

• Currently genomic focuses more on single Mendelian variants with large effect

• Expected that genomics soon should change to using at the same time numerous variants

Genomic Medicine Definitions

Manolio et. al. Genetic in Medicine 2013. 15(4): 258-267

• Some examples of genomic medicine projects

which are currently being implemented in

clinical practice include:

• Tumor-based genotype-driven treatment

• Risk/susceptibility testing in relatives of patients

with mutation-bearing cancer

• E.g.BRCA1 and BRCA2 mutations

• CYP2C19 and antiplatelet therapy

Genomic Medicine Projects Currently

In Implementation


• Genomic Medicine can help:

• Disease Risk Stratification

• Disease Diagnosis

• Disease Prognosis

• Selecting Optimal Therapy

• Disease Monitoring

Genomic Medicine

Goodman DM. et.al. JAMA 2013. Vol 309 No. 14 p. 1544

• BRCA1 and BRCA2 Gene Mutations:

• One of the best known and most widely discussed genetics test ever

• Overall, women have 12% lifetime risk of developing breast cancer

• Women with BRCA1 mutation have increased risk of developing breast cancer

• Women with BRCA2 mutation have increased risk of developing breast cancer

Disease Risk Stratification

National Cancer Institute at: www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet


• Overall about 1.3% women will develop

ovarian cancer

• Estimated that 44% of women with BRCA1

mutation will develop ovarian cancer

• Estimated that 17% of women with BRCA2

mutation will develop ovarian cancer




• Men with BRCA1 and BRCA2 mutations also

have an increased risk of breast cancer

• Men with BRCA1 and BRCA2 mutations also

have an increased risk of prostate cancer



• Diagnostic testing: using test to confirm the presence or absence of a disease

• Before the era of genomic medicine diagnosis was usually based on:

• Patient’s age

• Clinical features

• Laboratory test

• Imaging studies

Disease Diagnosis

• DNA Single-Gene Tests:

• RAS regulates cell growth and regulation

• RAS has three isoforms with KRAS most

commonly mutated

• KRAS mutated in 30%-50% of colon cancers

and is associated with:

• Shorter survival

• More aggressive tumors

Disease Prognosis


• Ability to define distinct subgroups within a disease improves ability to use targeted therapies

• Example includes Cystic Fibrosis (CF):

• CFTR gene gives instructions for making a protein called the cystic fibrosis transmembrane conductance regulator

• Cystic fibrosis transmembrane conductance regulator functions as a channel across the membrane of cells which produce mucus, sweat, saliva, etc.

Selecting Optimal Therapy

U.S. National Library of Medicine at: www.ghr.nlm.nih.gov/gene/CFTR


• Example includes Cystic Fibrosis (CF):

• Mutations in CFTR gene (e.g. E56K, P67L,

G551D, and some others) → Impaired chloride

channel function

• Novel small molecule, ivacaftor improves

function of specific mutations in CFTR and

patient outcome

Selecting Optimal Therapy

Kalydeco (ivacaftor) Tablets and Oral Granules Package Insert

• The risk of rejection with transplant:

• Highest in the early period immediately after transplant

• Declines over time

• Never goes away

• With cardiac and renal transplant need to do invasive biopsies to identify graft dysfunction

Disease Monitoring

• Potentially available less invasive

procedure, RNA profiling of:

• Peripheral blood for cardiac transplant

• Urine in kidney transplant

• RNA profiling technique allows to identify a

key set of transcripts to detect rejection of

transplanted grafts

Disease Monitoring

Horwitz PA. et.al. Circulation. 2004. 110:3815-3821

Li B et. al. N Engl Med. 2001. Vol. 344, No.13. 947-954.

Objective: Describe major methods

for evaluating evidence for

application of pharmacogenetics and

pharmacogenomics in the clinical

practice

• Criteria for evaluating genetic and

genomic tests include:

• Analytical validity

• Clinical validity

• Clinical utility

Evidence Supporting Clinical

Implementation of Pharmacogenomics

Holtzman NA , Watson MS. Final Report of the Task Force on Genetic Testing. Baltimore: Johns

Hopkins University Press: 1999. Promoting Safe and Effective Genetic Testing in the United States

• “Analytic validity: accuracy with which a particular

genetic characteristic can be identified in a laboratory

test” (Burke W et. al., 2002)

• Can use different protocols to test most genetic

characteristics of clinical interest

• There can be different technical issues when evaluating

analytic validity such as:

• Specific technical requirements for chosen assay

• The reliability of assay

• How much reliability varies from laboratory to laboratory

Analytical Validity

Burke W. et.al. Am J Epidemiol 2002. Vol.156 No.4 311-318

Burke W. Curr Protoc Hum Genet. 81:9.15.1-9.15.8

• Two different types of genetic tests:

• In-house: test by clinical laboratory (e.g.

laboratory-developed or home-grown)

• Manufacturer-developed: in vitro diagnostic

test for a specific drug that is critical for

safe and effective use of that drug (e.g.

companion diagnostic tests)

Analytical Validity

• The Clinical Laboratory Improvement Amendments (CLIA) governs quality standards for laboratory-developed tests

• CLIA regulations classifies laboratory testing based on the complexity of the tests as either:

• Waived or

• Non-waived → Molecular genetic testing is high-complexity

• Genetic test will not be used if it does not meet acceptable standards for analytic validity

Analytical Validity

Clinical Laboratory Improvement Amendments at: http://www.cms.hhs.gov/clia

• “Clinical validity: accuracy with which a

genetic test identifies a paricular clinical

condition” (Holtzman NA, Watson MA, 1999)

• Clinical validity is described by:

• Sensitivity

• Specificity

• Positive predictive value

• Negative predictive value

Clinical Validity


Holtzman, NA; Watson, MS. Final Report of the Task Force on Genetic Testing. Baltimore: Johns Hopkins University

Press: 1999. Promoting safe and effective genetic testing in the United States

• Sensitivity: among people with a particular

condition the proportion who have positive

test

• Specificity: among people who do not have

condition the proportion who have negative

test

• Positive predictive value

• Negative predictive value

Clinical Validity


• Positive predictive value: among people

with positive test the proportion who have

the condition

• Negative predictive value: among people

with negative test the proportion who have

the condition

Clinical Validity


• “Clinical utility: refers to the likelihood that the test will lead to an improved health outcome” (Burke et.al. 2002)

• The most important factors in determining clinical utility include:

• If the test or subsequent interventions lead to improved health outcomes in people with positive test result

• What risks happen as a result of testing

Clinical Utility

Burke W. et.al. Am J Epidemiol 2002. 156-311-318

Burke W. Curr Protoc Hum Genet. 2015. 81:9.15.1-9.15.8

• To completely measure clinical utility need to

include:

• Medical outcomes

• Social outcomes

• Subsequent interventions for peoples with

positive and negative test results

Clinical Utility


Objective: Evaluate strengths of

pharmacogenomics data

• Evaluation of drug-gene association should

include:

• Genetic variants of interest

• Evidence to support clinical utility

• Evidence-based guidelines (e.g. Clinical

Pharmacogenetic Implementation Consortium

guidelines with clear recommendation)

Drug-Gene Association

Arwood MJ et. al. Clin Transl Sci 2016. 9, 233-245

• Pharmacogenetic testing can be

performed:

• Reactively (at point-of-care):

• At the point of care to guide drug therapy or

• Pre-emptively (prospective):

• Obtained for future use when needed in

clinical setting

Pharmacogenetic Test Ordering and

Laboratory Processing

• Reactive/Point-of-Care Pharmacogenomic

Testing:

• Ordered when new medication is prescribed

• Pharmacogenomic test can be ordered for the

specific gene or genes that are involved in drug

metabolism, transport and/or target

• Delay in therapy until results are back

• Would still need interim medication

Point-of-Care vs. Preemptive/Prospective

Pharmacogenomic Testing

Haga SB and Moaddeb J. Pharmacogenet Genomics 2014. 24(3): 139-145

• Preemptive/Prospective Pharmacogenomic Testing:

• Involves analysis of a panel of genes with known associations to drug outcome

• Some populations may specifically benefit from pre-emptive testing such as populations with:

• Chronic conditions

• Risk factors for chronic conditions

• Preemptive pharmacogenomic tests results available whenever treatment is needed

Point-of-Care vs. Preemptive/Prospective

Pharmacogenomic Testing

Haga SB and Moaddeb J. Pharmacogenet Genomics 2014. 24(3): 139-145

• Growing list of drugs that have some reference to pharmacogenomic testing included in the drugs labeling

• Germline mutations (e.g. CYP metabolizing enzyme gene variations)

• Somatic mutations (e.g. KRAS expression in colorectal cancer)

• Some drugs are co-developed with pharmacogenetic tests

Challenges Associated with Producing

Evidence

• Most labels refer to reported pharmacogenetic

associations (e.g. altered drug metabolism or

drug-gene interactions)

• Most labels do not specifically recommend

testing before prescribing a drug or provide any

recommendation how prescribing should be

modified

Challenges Associated with Producing

Evidence

• Very important to develop clinical practice

guidelines for pharmacogenomics

• Major pharmacogenomics guidelines:

• The Clinical Pharmacogenetic Implementation

Consortium (CPIC), established 2009

Synthesizing Evidence-Based

Guidelines

Clinical Pharmacogenetics Implementation Consortium Guidelines at: www.cpicpgx.org/guidelines/


Consortium (CPIC):

• Formed by joint effort between the Pharmacogenomics

Knowledge Base (PharmGKB) and the National Institute

of Health (NIH)-funded Pharmacogenomics Research

Network

• Created to develop guidelines that would enable

translation of clinically relevant pharmacogenetic test

results into accountable therapeutic recommendation

• Provide guidance to clinicians how available genetic

test results should be used to improve drug therapy

Evidence-Based Guidelines

Clinical Pharmacogenetics Implementation Consortium: https://cpicpgx.org/


Consortium (CPIC):

• Genes-Drugs: CPIC assigns CPIC levels to

genes/drugs with:

• PharmGKB Clinical Annotation Levels of Evidence

• PharmGKB PGx level for FDA-approved drug labels

• Based on nomination to CPIC for consideration

Evidence-Based Guidelines: Evaluating

Strengths of Pharmacogenomics Data

Clinical Pharmacogenetics Implementation Consortium: https://cpicpgx.org/genes-drugs/



PharmGKB Clinical Annotation Levels of Evidence

1A Gene/drug pairs have sufficient evidence for at least one

prescribing action to be recommended

1B Gene/drug pairs have sufficient evidence for at least one


2A Gene/drug pairs have sufficient evidence for at least one


2B Gene/drug pairs have sufficient evidence for at least one


3 Not considered to have adequate evidence or actionability to

have prescribing recommendations

4 Not considered to have adequate evidence or actionability to

have prescribing recommendations

Clinical Pharmacogenetics Implementation Consortium: https://www.pharmgkb.org/page/clinAnnLevels

• PharmGKB PGx level for FDA-approved drug labels

of:

• Genetic testing required

• Genetic testing recommended

• Actionable

• Informative

• Based on nomination to CPIC for consideration



Clinical Pharmacogenetics Implementation Consortium Guidelines at: www.cpicpgx.org/guidelines/

• Guidelines need to be disseminated at:

• Peer reviewed journals

• Web sites

• National guidelines site

Clinical Practice Dissemination

• Selecting gene-drug pairs for implementation

• Institutional oversight of pharmacogenetic evidence

analysis and application to patient care

• Clinical support for health care providers

• Standardized laboratory ordering and interpretation

procedures

• Involvement of informational technology

• Education of different health care professionals

• Quality improvement and economic evaluations

Main Characteristics of Clinical

Pharmacogenetics Services


Need to obtain support from institutional leadership

Generally should obtain support from:

Administration

Medicine

Pharmacy

Laboratory

Health informational technology (IT)

Administrative and Stakeholder

Engagement


• Informational technology

• Scientific

• Education

• Ethical, legal, social and regulation issues

• Reimbursement

Major Barriers to the Clinical

Implementation of Pharmacogenetics

Klein ME et. al. Journal of Pharmaceutical Sciences 106. 2017. 2368-2379

• Some of potential barriers to the clinical

implementation of pharmacogenomic testing

include:

• Test-related barriers

• Knowledge barriers

• Evidence barriers

Barriers to the Clinical Implementation

of Pharmacogenomic Testing

Johnson JA. Pharmacogenomics. 2013. 14(7): 835-843.

• Many challenges in implementation of genomics

in clinical practice:

• Limited evidence

• Conflicting interpretation of benefit and value

• Limited access to genomic medicine expertise

and testing

• Lack of standards for genomic applications

• Lack of research funding and reimbursement

Challenges In Implementation of

Genomics in Clinical Practice


• Clinical pharmacogenetics implementation can

be incorporated into electronic health record

(EHR)

• EHR can help health care providers to easily

and quickly interpret and act on

pharmacogenetic test results

Clinical Pharmacogenomics

Implementation


• Need comprehensive and multidisciplinary

strategies to educate different health care

professionals

• Genetics/Genomics Competency Center (G2C2)

established to provide high quality

genetics/genomics educational resources for

health care educators and practitioners

Educational Needs to Support



National Human Genome Research Institute at: www.genomicseducation.net

• Genetics/Genomics Competency Center

(G2C2) has competencies map for:

• Nursing

• Physician assistant

• Pharmacist

• Genetic counselors

• Physicians




• Genetics/Genomics Competency Center (G2C2) competency map for pharmacists include:

• Basic genetic concepts

• Genetic and diseases

• Pharmacogenetics/pharmacogenomics

• Ethical, legal and social implications




• The Genetic Information Nondiscrimination Act

(GINA) of 2008 protects from discrimination

based on their genetic information in both:

• Health insurance (Title I) and

• Employment (Title II)

The Genetic Information

Nondiscrimination Act of 2008

National Human Genome Research Institute at: www.genome.gov/10001740/ethical-legal-and-social-

issues-in-genomic-medicine

• Informed consent: a process for getting permission

before conducting a healthcare intervention on a

person

• A health care provider may ask a patient to consent

to receive therapy before providing it or a clinical

researcher may ask a research participant before

enrolling that person into a clinical trial

Informed Consent and Patient-Provider

Communication

• Different factors should be taken into considerations when designing an informed consent process and consent form such as:

• Information is personal and unique to each individual

• If information is going to be stored and used indefinitely

• Need to inform individuals about susceptibility to a broad range of conditions (some of which are unexpected given personal or family history)

• If tests carry with them risks that are uncertain or unclear

• Raise privacy concerns (due to the risk of re-identification)

Informed Consent for Pharmacogenomics

National Human Genome Research Institute at: https://www.genome.gov/about-genomics/policy-

issues/Informed-Consent

FDA Drug Labels and Pharmacogenomics

U.S. Food and Drug Administration at: www.fda.gov/drugs/scienceresearch/ucm572698.htm

• Drug labeling may include information on

genomic biomarkers which can define:

• Drug exposure and clinical response variability

• Risk for adverse events

• Genotype-specific dosing

• Mechanisms of drug action

• Polymorphic drug target and disposition genes

• Trial design

Objective: Apply

pharmacogenomics data for

different disease states

• Psychiatry

• Cardiology

• Neurology

• Infectious diseases

• Hematology/Oncology

• Pulmonology

• Anesthesiology

• Gastroenterology

Pharmacogenomics Data for Different

Disease States

U.S. Food and Drug Administration at: www.fda.gov/drugs/science-research-drugs/table-

pharmacogenomic-biomarkers-drug-labeling

• Oncology has the most success in search for

useful biomarkers

• With the success of targeted therapies there is

a huge interest in finding more biomarkers to

help to identify patients with the greatest

likelihood of receiving benefits from a specific

therapy

Pharmacogenomics in Oncology Research

• In pharmacogenomics research in

oncology very important both:

• Somatic mutations and

• Germline mutations

Pharmacogenomics in Oncology

Research

Wheeler HE et. al. Nat Rev Genet. 2013. 14(1): 23-34

• Somatic mutations: present in the cancer

tissue and can define cancer subtype

• Can develop medications that target specific

receptor expressed on the cancer cell

• Examples include: Monoclonal antibodies

panitumumab and cetuximab directed

against the epidermal growth factor receptor

(EGRF)



• Germline mutations:

• Present in patient’s normal tissues

• Affect pharmacokinetics and pharmacodynamics

of a medication

• Example include: Mercaptopurine used for the

treatment of acute lymphoblastic leukemia (ALL)

• Patients with inactive variant of TPMT allele need

to have mercaptopurine dose reduced due to the

increased toxicity



1.Pharmacogenetics has potential

to? (Select all that apply)

a. Improve patient outcome

b. Decrease risks of adverse events

c. Promote use of targeted cost-

effective therapy for patient care

2.Genomic medicine can help with which

of the following? (Select all that apply)

a. Disease risk stratification

b. Disease diagnosis

c. Disease prognosis

d. Selecting optimal therapy

e. Disease monitoring

3. Analytic validity is defined as?

a. Accuracy with which a specific

characteristic is identified in the

laboratory test

b. Accuracy with which a genetic test

identifies a specific clinical condition

c. Risk and benefits that result from genetic

test use

4. Which of the following is true about

reactive pharmacogenetic tests?

a. They are ordered when the new medication

is prescribed

b. Obtained for future use when needed in the

clinical setting

c. Also called prospective testing

5. The Genetic Information

Nondiscrimination Act of 2008 protects

from discrimination based on genetic

information in?

a. Health insurance only

b. Employment only

c. Health insurance and employment

d. Neither health insurance nor employment

• Arwood MJ, Chumnumwat S, Cavallary LH, Nutescu EA and Duarte JD. Implementing Pharmacogenomics at Your Institution: Establishment and Overcoming Implementation Challenges. Clinical and Translational Sciences 9, 2016. 233-245. doi:10.1111/cts.12404

• Burke W, Austin MA, Gwinn M, Guttmacher A, Haddow J…Wiesner GL. Genetic Test Evaluation: Information Needs of Clinicians Policy Makers, and the Public. American Journal of Epidemiology. Vol. 165, No. 4 311-318. doi:10.1093/aje/kwf055

• Burke W. Genetic Test: Clinical Validity and Utility. Curr Protoc Hum Genet. 81:9.15.1-9.15.8. doi: 10.1002/0471142905.hg0915s81

• Clinical Pharmacogenetics Implementation Consortium: https://cpicpgx.org/ Accessed: 7/30/2019.

• Clinical Pharmacogenetics Implementation Consortium: https://cpicpgx.org/genes-drugs/Accessed: 7/30/2019.

• Clinical Pharmacogenetics Implementation Consortium: https://www.pharmgkb.org/page/clinAnnLevels Accessed: 7/30/2019.

• Clinical Pharmacogenetics Implementation Consortium Guidelines at: https://cpicpgx.org/guidelines/ Accessed: 7/30/2019.

• Clinical Laboratory Improvement Amendments at: http://www.cms.hhs.gov/clia Accessed: 7/30/2019.

• Goodman DM, Lynm C, Livingston EH. Genomic Medicine. JAMA (The Journal of American Medical Association). 2013. 309(14):1544

• Haga SB, Moaddeb J. Comparison of Delivery Strategies for Pharmacogenetic Testing Services. Pharmacogenet Genomics. 2014. 24(3): 139-145. doi:10.1097/FPC.0000000000000028

References

https://cpicpgx.org/

https://cpicpgx.org/genes-drugs/

https://www.pharmgkb.org/page/clinAnnLevels

https://cpicpgx.org/guidelines/

• Holtzman, NA; Watson, MS. Final Report of the Task Force on Genetic Testing.

Baltimore: Johns Hopkins University Press: 1999. Promoting safe and effective

genetic testing in the United States

• Horwitz PA, Tsai EJ, Putt ME, Gilmore JM, Lepore JJ...Cappola TP. Detection of

Cardiac Allograft Rejection and Response to Immunosuppressive Therapy With

Peripheral Blood Gene Expression. Circulation. 2004. 110:3815-3821. doi:

10.1161/01.CIR.0000150539.72783.BF

• Johnson JA. Pharmacogenomics in clinical practice: how far have we come and

where are we going? Pharmacogenomics. 2013. 14(7): 835-843. doi:10.2217/pgs.

13.52.

• Kalydeco Package Insert. Boston, MA. Vertex Pharmaceutical Incorporated; April

2019.

• Klein ME, Parvez MM, Shin JG. Clinical Implementation of Pharmacogenomics for

Personalized Precision Medicine: Barriers and Solutions. Journal of Pharmaceutical

Sciences. 2017. 106. 2368-2379. doi: 10.1016/j.xphs.2017.04.051

• Li B, Hartono C, Ding R, Sharma VK, Ramaswamy R….Suthanthiran M. Noninvasive

Diagnosis of Renal-Allograft Rejection by Measurement of Messenger RNA for

Perforin and Granzyme B in Urine. The New England Journal of Medicine. 2001.

Vo. 344, No.13. 947-954.

References

• Manolio TA, Chisholm RL, Ozenberger B, Roden DM, Williams MS…Ginsburg GS.

Implementing genomic medicine in the clinic: the future is here. Genetic in Medicine.

2013. Vol 15, Number 4, 258-267. doi:10.1038/gim.2012.157

• National Cancer Institute at: www.cancer.gov/about-cancer/causes-

prevention/genetics/brca-fact-sheet Accessed: 7/30/2019.

• National Human Genome Research Institute at: www.genome.gov/27527652/genomic-

medicine-and-health-care/ Accessed: 7/30/2019.

• National Human Genome Research Institute at: www.genomicseducation.net

• National Human Genome Research Institute at: www.genome.gov/10001740/ethical-

legal-and-social-issues-in-genomic-medicine Accessed: 7/30/2019.

• National Human Genome Research Institute at: https://www.genome.gov/about-

genomics/policy-issues/Informed-Consent Accessed: 7/30/2019.

• U.S. Food and Drug Administration at:

www.fda.gov/drugs/scienceresearch/ucm572698.htm Accessed: 7/30/2019.

• U.S. Food and drug Administration at: www.fda.gov/drugs/science-research-

drugs/table-pharmacogenomic-biomarkers-drug-labeling Accessed: 7/30/2019.

• U.S. National Library of Medicine at: www.ghr.nlm.nih.gov/gene/CFTR Accessed:

7/30/2019.

• Wheeler HE, Maitland ML, Dolan ME, Cox NJ, Ratain MJ. Cancer pharmacogenomics:

strategies and challenges. Nat Rev Genet. 2013. 14(1): 23-34 doi: 10.1038/nrg3352.

References

http://www.genome.gov/10001740/ethical-legal-and-social-issues-in-genomic-medicine

https://www.genome.gov/about-genomics/policy-issues/Informed-Consent

http://www.fda.gov/drugs/science-research-drugs/table-pharmacogenomic-biomarkers-drug-labeling

http://www.ghr.nlm.nih.gov/gene/CFTR

Documents

New Approach to Medicine: Personalized Medicine ... · • Pharmacogenetics: the study of variability in drug response due to genetics; relation to genes which determine drug metabolism