Pharmacogenetics Pharmacogenomics Jozef Glasa Slovak Medical University Bratislava

Pharmacogenetics & Pharmacogenomics Jozef Glasa Slovak Medical University Bratislava, Slovak Republic

Pharmacogenetics - the study of variability in drug response due to genetic factors in individuals or populations. - uses genomically derived information in identifying specific subpopulations and may be useful in order to target pharmaceutical agents. Pharmacogenomics - applies the information on genome (DNA) or its products (RNA, proteins) to drug design, discovery, and clinical development, reflecting the state or responses at cellular, tissue, individual or population level. EMEA/CPMP/3070/01, Dec. 2001

Pharmacogenetics & Pharmacogenomics Problems and Perspectives • great expectations: patients, physicians, scientists, public, pharmaceutical industry • old and novel ethical considerations • present challenges and future perspectives

Great expectations

Great Expectations • patients (new effective preventive and treatment options, safe therapies, better quality of life, health costs savings, . . . ) • physicians (effective preventive and treatment options, safe(r) therapies, expenditures savings(? ), professional success, . . . ) • scientists (new career and job opportunities, . . . ) • public (better health & health care; health care sector expenditures savings; accessibility; fairness; etc. ) • pharmaceutical industry (new drugs, new target populations, new market possibilities; development, new technologies; image building, prestige; safe(r) business, profits; possibly some withdrawn drugs’ resurrection; clinical testing costs savings. . . )

Pharmacogenetics - predicted developments • Establishment of prescribing guidelines, based on clinical studies, for drugs that are subject to substantial polymorphic metabolism • Prescribing advice will relate dose to genotype and will highlight the possibility of drug interactions when multiple drugs are prescribed concomitantly • Establishment and recording of individual patient genotypes - „personal pharmacogenetic profiles“ • Pharmacogenetic testing will substantially reduce the need for hospitalisation, and its associated costs, because of ADRs • Development of new drugs for patients with specific genotypes - „drug stratification“ Wolf, C. R. , Smith, G. , Smith, R. L. , BMJ, 2000, 320: 987 - 990.

Evans, W. E. , Johnson, J. A. , Annu. Rev. Genomics Hum. Genet. , 2001, 2: 9 - 39.

http: //genetics. glaxowelcome. com

Pharmaco/genetics/genomics Research Old and Novel Ethical Considerations

Societal Concerns Arising from the New Genetics (1) • Fairness in the use of genetic information by insurers, employers, courts, schools, adoption agencies, and the military, among others. • Privacy and confidentiality of genetic information. • Psychological impact and stigmatization due to an individual's genetic differences. • Reproductive issues including adequate informed consent for complex and potentially controversial procedures, use of genetic information in reproductive decision making, and reproductive rights. • Clinical issues including the education of doctors and other health service providers, patients, and the general public in genetic capabilities, scientific limitations, and social risks; and implementation of standards and quality-control measures in testing procedures. Human Genome Project - ELSI

Societal Concerns Arising from the New Genetics (2) • Uncertainties associated with gene tests for susceptibilities and complex conditions (e. g. , heart disease) linked to multiple genes and gene-environment interactions. • Conceptual and philosophical implications regarding human responsibility, free will vs. genetic determinism, and concepts of health and disease. • Health and environmental issues concerning genetically modified foods (GM) and microbes. • Commercialization of products including property rights (patents, copyrights, and trade secrets) and accessibility of data and materials. Human Genome Project - ELSI

Pharmaco/genetics/genomics Research Old and Novel Ethical Considerations • ‘Good‘ vs. ‘bad‘ allocation of scarce resources – cons PGx: more urgent healthcare problems – pros PGx: save costs of ADRs and ineffective therapies, save on effective therapeutic process, etc. • Fair distribution of burdens & benefits developing pharmacogenetics in – intially high costs of PGx therapies - inequal access – conflicts of interests (researchers & enterpreuners, quality, validity and safety of research) • Ethical use of individualized medicine – PGx information use in healthcare practice – environmental factors vs. PGx (food, habits, exposures to adverse factors, etc. ) • Whose rights predominates? – children/minors vs. parents – intersts of third parties (science, society, other diseased persons, future generations, etc. ) Barash, C. I. , www. actionbioscience. org, Febr. 2001.

Pharmaco/genetics/genomics Research Old and Novel Ethical Considerations • Recruitment and selection of PGx research subjects – genotyping - eligibility criterion? (genotype-based selection) – unfair representation in trials, loss of benefits of participation – reduction of numbers of participants - affection of external validity of the study (? ), applicability in clinical practice (? ) • PGx research on families and populations – – genetic info: personal, familial, communal dynamics, social significance of family, new family - health provider relationship, „the principle of respect for communities“ • Risk/benefit assessment – benefits PGx information use; PGx info vulnerability – risk of stigmatization, discrimination, social ramification for an individual, family, population group, etc. • Pharmacoeconomic considerations and equity – possible savings (drug R&D, ADRs, ineffective therapies) – reduction of users populations/market by PGx testing – Should a pharmacompany be obliged to offer genotyping? Issa, A. M. , Ti. PS, 2000, 21: 247 -249.

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