Ethical perspectives on pharmacogenomic profiling in the drug development process (original) (raw)
Evans, W. E. & Relling, M. V. Pharmacogenomics: translating functional genomics into rational therapeutics. Science286, 487–491 (1999). ArticleCAS Google Scholar
Rioux, P. P. Clinical trials in pharmacogenetics and pharmacogenomics: methods and applications. Am. J. Health Syst. Pharm.57, 887–898 (2000). ArticleCAS Google Scholar
McLeod, H. L. & Evans, W. E. Pharmacogenomics: unlocking the human genome for better drug therapy. Annu. Rev. Pharmacol. Toxicol.41, 101–121 (2001). ArticleCAS Google Scholar
Norton, R. M. Clinical pharmacogenomics: applications in pharmaceutical R & D. Drug Discov. Today6, 180–185 (2001).This paper provides a good overview of the types of pharmacogenomics trial that are underway at present, and why the industry might view pharmacogenomics as a potentially powerful tool in its armament. Article Google Scholar
Classen, D. C., Pestotnik, S. L., Evans, R. S. & Lloyd, J. F. Adverse drug events in hospitalized patients. Excess length of stay, extra costs, and attributable mortality. JAMA277, 301–306 (1997). ArticleCAS Google Scholar
Lazarou, J., Pomeranz, B. H. & Corey, P. N. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA279, 1200–1205 (1998). ArticleCAS Google Scholar
Phillips, K. A., Veenstra, D. L., Oren, E., Lee, J. K. & Sadee, W. Potential role of pharmacogenomics in reducing adverse drug reactions. JAMA286, 2270–2279 (2001).This is an important systematic review that gives the reader a good understanding of how genetic polymorphisms might be associated with adverse drug reactions. ArticleCAS Google Scholar
Primohamed, M. & Park, B. K. Genetic susceptibility to adverse drug reactions. Trends Pharmacol. Sci.22, 298–305 (2001). Article Google Scholar
Persidis, A. Pharmacogenomics. Nature Biotechnol.18, IT40–IT42 (2000). Google Scholar
Arledge, T., Freeman, A., Arbuckle, J., Mosteller, M. & Manasco, P. Applications of pharmacogenetics to drug development: the Glaxo Wellcome experience. Drug Metab. Rev.32, 387–394 (2000). ArticleCAS Google Scholar
Furuta, T. et al. Effect of genotypic differences in CYP2C19 on cure rates for Helicobacter pylori infection by triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin. Clin. Pharmacol. Ther.69, 158–168 (2001). ArticleCAS Google Scholar
Lessard, E. et al. Influence of CYP2D6 activity on the disposition and cardiovascular toxicity of the antidepressant agent venlafaxine in humans. Pharmacogenetics9, 435–443 (1999). ArticleCAS Google Scholar
Drazen, J. M. Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment. Nature Genet.22, 168–170 (1999). ArticleCAS Google Scholar
Israel, E. et al. Effect of polymorphism of the β(2)-adrenergic receptor on response to regular use of albuterol in asthma. Int. Arch. Allergy Immunol.124, 183–186 (2001). ArticleCAS Google Scholar
Poirier, J. et al. Apolipoprotein E4 allele as a predictor of cholinergic deficits and treatment outcome in Alzheimer disease. Proc. Natl Acad. Sci. USA92, 12260–12264 (1995). ArticleCAS Google Scholar
Richard, F. et al. APOE genotyping and response to drug treatment in Alzheimer's disease. Lancet349, 539–540 (1997). ArticleCAS Google Scholar
Rigaud, S. et al. The apolipoprotein E4 allele and the response to tacrine therapy in Alzheimer's disease. Eur. J. Neurol.7, 255–258 (2000). ArticleCAS Google Scholar
Arranz, M. et al. Association between clozapine response and allelic variation in 5-HT2A receptor gene. Lancet346, 281–282 (1995). ArticleCAS Google Scholar
Masellis, M. et al. Serotonin subtype 2 receptor genes and clinical response to clozapine in schizophrenia patients. Neuropsychopharmacol.19, 123–132 (1998). ArticleCAS Google Scholar
Joober, R. et al. T102C polymorphism in the 5HT2A gene and schizophrenia: relation to phenotype and drug response variability. J. Psych. Neurosci.24, 141–146 (1999). CAS Google Scholar
Kuivenhoven, J. A. et al. The role of a common variant of the cholesteryl ester transfer protein gene in the progression of coronary atherosclerosis. New Engl. J. Med.338, 86–93 (1998). ArticleCAS Google Scholar
Drazen, J. M. et al. Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment. Nature Genet.22, 168–170 (1999). ArticleCAS Google Scholar
World Health Organization. Proposed International Guidelines on Ethical Issues in Medical Genetics and Genetics Services <www.who.int/ncd/hgn/hgnethic.htm> (1997).
Holtzman, N. A. & Watson, M. S. (eds) Promoting Safe and Effective Genetic Testing in the United States: Final Report of the Task Force on Genetic Testing (National Institutes of Health – Department of Energy Working Group on Ethical, Legal and Social Implications of Human Genome Research Task Force on Genetic Testing, Washington DC, 1997). Google Scholar
Secretary's Advisory Committee on Genetic Testing. Enhancing the Oversight of Genetic Tests: Recommendations of the SACGT (2000).
Robertson, J. A. Consent and privacy in pharmacogenetic testing. Nature Genet.28, 207–209 (2001).This paper provides an overview of some of the consent and privacy issues that could potentially be ethically challenging once pharmacogenetics is used routinely in clinical practice. ArticleCAS Google Scholar
Issa, A. M. Ethical considerations in clinical pharmacogenomics research. Trends Pharmacol. Sci.21, 247–250 (2000). ArticleCAS Google Scholar
Title 45, US Code of Federal Regulations (CFR), part 46. Protection of human subjects. 45CFR46.111(a)(1) <http://ohrp.osophs.dhhs.gov/>.
Friedman, L. M., Furberg, C. D. & DeMets, D. L. Fundamentals of Clinical Trials (Wright, Boston, 1996). Google Scholar
Council for International Organizations of Medical Sciences. International Ethical Guidelines for Biomedical Research Involving Human Subjects (Geneva, 1993).
Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans. A Report by a Working Group of the Three Federal Funding councils: Medical Research Council of Canada, Natural Sciences and Engineering Research Council of Canada, and Social Sciences and Humanities Research Council of Canada (1998).
World Medical Association Declaration of Helsinki Ethical Principles for Medical Research Involving Human Subjects, Adopted by the 18th WMA General Assembly Helsinki, Finland, 1964, and amended by the 52nd WMA General Assembly, Edinburgh, Scotland (2000).
Emmanuel, E., Wendler, D. & Grady, C. What makes clinical research ethical? JAMA283, 2701–2711 (2000). Article Google Scholar
Murphy, M. P. et al. Prospective CYP2D6 genotyping as an exclusion criterion for enrolment of a Phase III clinical trial. Pharmacogenetics10, 583–590 (2000). ArticleCAS Google Scholar
Weber, W. W. Pharmacogenetics (Oxford Univ. Press, New York, 1997). Google Scholar
March, R. Pharmacogenomics: the genomics of drug response. Yeast17, 16–21 (2000). ArticleCAS Google Scholar
Silverman, E. K. & Palmer, L. J. Case–control association studies for the genetics of complex respiratory diseases. Am. J. Respir. Cell. Mol. Biol.22, 645–648 (2000). ArticleCAS Google Scholar
Bird, T. D., Jarvik, G. P. & Wood, N. W. Genetic association studies: genes in search of diseases. Neurology57, 1153–1154 (2001). ArticleCAS Google Scholar
Roden, D. M. & George, A. L. The genetic basis of variability in drug responses. Nature Rev. Drug Discov.1, 37–44 (2002). ArticleCAS Google Scholar
McCarthy, J. J. & Hilfiker, R. The use of single-nucleotide polymorphism maps in pharmacogenomics. Nature Biotechnol.18, 505–508 (2000). ArticleCAS Google Scholar
Cardon, L. R., Idury, R. M. & Harris, T. J. R. Testing drug response in the presence of genetic information: sampling issues for clinical trials. Pharmacogenetics10, 503–510 (2000). ArticleCAS Google Scholar
Long, A. D. & Langley, C. H. The power of association studies to detect the contribution of candidate genetic loci to variation in complex traits. Genome Res.9, 720–731 (1999). CAS Google Scholar
Blacker, D. 2-Macroglobulin is genetically associated with Alzheimer disease. Nature Genet.19, 357–360 (1998). ArticleCAS Google Scholar
Dow, D. J. et al. α2-Macroglobulin polymorphism and Alzheimer disease risk in the UK. Nature Genet.22, 16–17 (1999). ArticleCAS Google Scholar
Rudransingham, V. et al. α2-Macroglobulin gene and Alzheimer disease. Nature Genet.22, 17–19 (1999). Article Google Scholar
Rogaeva, E. A. et al. An α2-Macroglobulin insertion–deletion polymorphism in Alzheimer disease. Nature Genet.22, 19–21 (1999). ArticleCAS Google Scholar
Butler, D. Epidemiology set to get fast-track treatment. Nature414, 139 (2001) ArticleCAS Google Scholar
Albert, S. M., Sano, M. & Marder, K. Participation in clinical trials and long-term outcomes in Alzheimer's disease. Neurology49, 38–43 (1997). ArticleCAS Google Scholar
Knopman, D. et al. Long-term tacrine (Cognex) treatment: effects on nursing home placement and mortality. Neurology47, 166–177 (1996). ArticleCAS Google Scholar
Issa, A. M. & Keyserlingk, E. W. Apolipoprotein E genotyping for pharmacogenetic purposes in Alzheimer's disease: emerging ethical issues. Can. J. Psychiatry45, 917–922 (2000). ArticleCAS Google Scholar
Sterne, J. A. C. Sifting the evidence – what's wrong with significance tests? Br. Med. J.322, 226–231.
Becker, R. E. Modifying clinical trial designs to test treatments for clinical significance in individual patients. Clin. Drug Invest.21, 727–733 (2001). Article Google Scholar
Chen, S. et al. A genetic bias in clinical trials? Cytochrome P450-2D6 (CYP2D6) genotype in general vs selected healthy subject populations. Br. J. Clin. Pharmacol.44, 303–304 (1997). CAS Google Scholar
Bodenheimer, T. Uneasy alliance: clinical investigators and the pharmaceutical industry. New Engl. J. Med.342, 1539–1544 (2000). ArticleCAS Google Scholar
Zhao, H. Y. Family-based association studies. Stat. Methods Med. Res.9, 563–587 (2000). ArticleCAS Google Scholar
Jorde, L. B. Linkage disequilibrium and the search for complex disease genes. Genome Res.10, 1435–1444 (2000). ArticleCAS Google Scholar
Cardon, L. R. & Bell, J. L. Association study designs for complex diseases. Nature Rev. Genet.2, 91–99 (2001).A thorough review that discusses different designs of genetic-association studies and their inherent limitations. Lessons from these studies need to be considered in thinking about the future design of pharmacogenomics trials. ArticleCAS Google Scholar
Regaldo, A. Inventing the pharmacogenomics business. Am. J. Health Syst. Pharm.56, 40–50 (1999). Article Google Scholar
Persidis, A. The business of pharmacogenomics. Nature Biotechnol.16, 209–210 (1998). ArticleCAS Google Scholar
Food and Drug Administration. Miscellaneous provisions relating to the Orphan Drug Act. Food and Drug Administration (cited 01 Mar 02) <htpp://www.fda.gov/opacom/laws/orphandg.htm> (2001).
Europarliament. Scientific and Technological Options Assessment. Orphan Drug Status Initiatives in the Different Countries (cited 01 Mar 02) <http://www.europarl.eu.int/home/default_en.htm>.
Moses, H. & Martin, J. B. Academic relationships with industry: a new model for biomedical research. JAMA285, 933–935 (2001). Article Google Scholar
Bains, W. The long-term value of genomics companies. J. Chem. Technol. Biotechnol.75, 883–900 (2000). ArticleCAS Google Scholar
Aronowitz, R. A. Making Sense of Illness: Science, Society and Disease. (Cambridge Univ. Press, Cambridge, UK, 1998). Google Scholar
Todd, J. A. Interpretation of results from genetic studies of multifactorial diseases. Lancet354 (Suppl. 1), 15–16 (1999). Article Google Scholar
Patino, C. M. & Martinez, F. D. Interactions between genes and environment in the development of asthma. Allergy56, 279–286 (2001). ArticleCAS Google Scholar
Ingelman-Sundberg, M. Pharmacogenetics: an opportunity for a safer and more efficient pharmacotherapy. J. Int. Med.250, 186–200 (2001). ArticleCAS Google Scholar