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Integration of Pharmacogenomics In To Clinical Trials
By Yawo M Akrodou PHD
MS Clinical Research Administration
Walden University June 2016
Presentation Overview
Definition of Pharmacogenomics
Causes of Using Pharmacogenomics in Clinical Trial
Contributions of Pharmacogenomics
Limitation of Pharmacogenomics
Challenges of Pharmacogenomics
Advancing Pharmacogenetics
Prospective of Pharmacogenetics
Recommendation
Conclusions
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Pharmacogenomics use in clinical trials,
is it Worthy?
© 2014 Walden University, LLC
3
Definition: Pharmacogenomics Concepts
• Mixing of pharmacology and genetics practices
• Investigating various drug responses due to genes
• Prediction of genetics reactions to drug side effect and adverse
• Making drug according to genetic information
• Individualization of drug therapy
• One Drug Does Not Fit All”
• Process to get the right drug to right patient
(Issa, 2000)
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Definition: Pharmacogenomics Methods
• Use of the DNA/RNA or protein sequencing tool strategy to
develop reliable markers that may help to predict drug
responses
• Use of protein sequencing to catalogue biomarker of specifics
drug response in disease treatment for drug discovery
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Definition: Pharmacogenetics' Methods
• The study of inherited factors and their influence on drug
response variability
• Use genes sequencing result to discover drugs
(Cohen, 2008)
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Causes of Using Pharmacogenomics in Clinical Trial :
Pharmaceutical Industry Challenges
Increase of drug recalls from the markets
Failure to make new drug safe and effective
Long period of clinical trial conducts (i.e.12 years)
Financial burden of clinical trial organization
Regulatory pressure on drug making industry
Globalization fueling competition
Need to make drug for complex disease
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Causes of Using Pharmacogenomics in Clinical Trial : Classic
Clinical Trial Limitation
• Use of pharmacology limited process
• Use of chemical-driven limited methods
• Cannot predict genetic induced drug reaction
• Hypothesis driven strategy
• Lack to detect all pre-market drug side effect
• Lack of knowledge of inter-individual drug responses
• Produce drugs with high individual incidence
• Obsoletes strategy and limited innovation
• Fig 1. Clinical trial of new drugs. Source : Shaw, D.D.(2013).
•
Fig 1. Clinical trial of new drugs. Source : Shaw, D.D.(2013).
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Causes of Using Pharmacogenomics:
Increasing Emerging Genetic Disorder
Source: Szade, et al.2013
Contributions of Pharmacogenomics: Innovation of Drug
Discovery Process
• Innovation of drug discovery
• Targeted drug development
• Solve inter-individual drug responses
• Tailoring drug therapy to individual
• Individualized drug uses
• Reduce drug interaction incidence
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Limitation of Pharmacogenomics
• Cannot cure all diseases
• Gene-gene interaction
• Gene regulation anomalies
• Unforeseen mutation
• Higher number of genes in multigene etiology
• Limitation of genes sequencing and profiling
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Contributions of Pharmacogenomics: Quality Drug Making
• Make drugs according to genes
variants
• Adjusting drug-doses according
• to genetic variants
• Provide drug according to genetic
deficiencies in :
Receptors,
Metabolizer
Transporter
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Figure3 . Example of gene therapy of ADA
defiecieny. Source .Szade, et al.(2013)
Contributions of Pharmacogenomics: Monogenic and Multigene
Treatment
Monogenic disease treatment
– Transduction method
– Transgene method
– Enzyme replacement
Figure2 : One of the first controlled trial of genes therapy in 1990
Source: Szade, et al.2013
Multigene Treatment
– Genes interaction test treatment
– Genes therapy to enhance treatment
10-20% pharmacogenomics treatment of
Parkinson’s Disease
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Challenges of Pharmacogenomics
• Lack of uniform method across biotech companies for DNA
treatment
• Lack of regulatory for patient safety and privacy information
protection
• Non uniform methodology for data process
• Complex of genomics and genetic application
• Unknown cost-effectiveness
• Lack of Education
• (Gudmundur, Thorisson, & Brookes, 2009).
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Advancing Pharmacogenetics: Best Pharmacogenomics Practices
• Use of genomics practices:
– Predict lead compounds reaction candidate genes in preclinical
trial
– Determine earlier subgroup genetic reaction to the compound in
clinical trial Phase I & II.
– Gather extensive data for drug registration and beyond phases
III, IV and V.
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Advancing Pharmacogenetics
Advocate for more FDA and ICH Framework establishments
Encourage the Industry of Pharmacogenomics Working Group
(I-PWG) and Personalized Medicine Initiative to have uniform
regulation and pharmacogenomics working method.
Continual cost-effectiveness assessment
Stakeholder education
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Social Implications
Enhancement of individual health
Revive Pharmacy-business
Increase drug access
Decrease health disparity
Promote new era of individualized treatments (Glass,et
al,2000)
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Prospective of Pharmacogenetics
Prospective
• Promising future
• Opportunity for drug discovery and development Innovation
• High level of cost-effectiveness
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Prospective of Pharmacogenetics
Develop rigorous methods for sample and data collection
Create general consent for proper information disclosure and
recruitment
Develop a protocol template which satisfies regulatory and
ethical standards
Devise the transparent methodology for statistical data analysis
and their translational process into clinical
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Conclusion
• Pharmacogenetics drug developments, although bearing
scientific promise, raise ethical concerns about conducting
research with human subjects, particularly as regards
confidentiality, risk–benefit analysis, DNA-banking.
• In addition, pharmacoeconomic issues remain to be resolved,
but pharmacogenetics and pharmacogenomics hold a
promising future and the potential to innovate the drug
discovery process (Issa, 2002).
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References
Cockburn, M. L. (2004). The changing structure of the pharmaceutical industry drug development
under today's new institutional arrangement. Health Affair. 23(1),10-22
doi: 10.1377/hlthaff.23.1.10
Cohen, N. (2008). Pharmacogenomics and Personalized Medicine. Louisville, KY: Humana
Press.
Issa, M. A. (2002). Ethical perspectives on pharmacogenomics profiling in the drug development
process. Reviews Drug Discovery .1(4),300-308. doi:10.1038/nrd771
Glass, W.G., McDermott, D. H., & Lim, J. K., Lekhong, S., Yu, F. S., Frank, A. W…. (2006).
CCR5 deficiency increases risk of symptomaticWest Nile virus infection. Journal of
Experimental Medicine, 203(1), 35–40
Gudmundur, A., Thorisson, J. M., & Brookes, A. J. (2009). Genotype–phenotype databases:
Challenges and solutions for the post-genomic era. Nature Reviews Genetics 10(1), 9–18.
doi:10.1038/nrg2483Szade K, Bukowska-Strakova K, Nowak WN, Szade A, Kachamakova-Trojanowska N, Zukowska
M, et al…… (2013) Murine Bone Marrow Lin−Sca-1+CD45− Very Small Embryonic-Like
(VSEL) Cells Are Heterogeneous Population Lacking Oct-4A Expression. PLoS ONE 8(5):
e63329. doi:10.1371/journal.pone.0063329
Shaw, D.D.(2013).Clinical Trial Phases. MSCreation.Retrieved from http://mscreations.org/clinical-trial-phases
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Acknowledgement
I would like to thank our Instructor for making
this presentation possible.
Dr. Shazia Qureshy
Thank you very much.
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