Transcript Ethics of Pharmacogenetics Research: A ‘Dark – Bright’ Future?

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market possibilities; development, new technologies; image building, prestige; safe(r) business, profits; possibly some withdrawn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.
Evans, W. E., Johnson, J. A., Annu. Rev. Genomics Hum. Genet., 2001, 2: 9 - 39.
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
in developing pharmacogenetics
– 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., TiPS, 2000, 21: 247-249.
Thank you for your attention!