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Ethical perspectives on pharmacogenomic profiling in the drug development process

Nature Reviews Drug Discovery volume 1, pages 300–308 (2002)Cite this article

Key Points

  • One goal of using pharmacogenomics in the drug development process is to determine genotype–phenotype correlations for drug responsiveness and adverse events.

  • An ideal future aim of pharmacogenomic profiling in clinical trials is to eventually develop therapies that are customized or tailored to individuals.

  • Although the objectives of pharmacogenomics are attractive, they raise a host of scientific, ethical and social concerns.

  • In anticipation of further scientific evidence for pharmacogenomics-based predictors of drug responsiveness, it is important to examine issues of ethical concern that are related to the use of pharmacogenomic profiling in clinical trials and the drug development process.

  • This paper addresses some of the ethical concerns that are raised by the integration of genotyping into the drug development process from four perspectives: clinical-trial design; subject stratification; some new social risks; and economic issues.

  • Some recommendations for future research, bioethical analysis and policy planning are proposed.

Abstract

Pharmacogenomics, which is a field that encompasses the study of genetic polymorphisms that underlie individual differences in drug response, is rapidly advancing. The potential for the widespread use of pharmacogenomics in the drug development process merits an examination of its fundamental impact on clinical-trial design and practice. This article provides a critical analysis of some of the issues that pertain to pharmacogenomics in the drug development process. In particular, four areas will be discussed: clinical-trial design; subject stratification; some new social risks; and economic concerns. Recommendations are offered for addressing the issues that are discussed and anticipating the regulatory needs for pharmacogenomics-based trials.

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Figure 1: An ultimate clinical goal of pharmacogenomics.

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Acknowledgements

A.M.I. gratefully acknowledges the support of the Fonds de la recherche en santé du Québec (FRSQ). This paper was written during the author's tenure as a Fellow of Medical Ethics at Harvard Medical School.

Author information

Authors and Affiliations

  1. Clinical Ethics Center, Memorial Medical Center, Southern Illinois University School of Medicine, 701 North First Street, Springfield, 62781-0001, Illinois, USA

    Amalia M. Issa

  2. Division of Medical Ethics, Department of Social Medicine, Harvard Medical School, 641 Huntington Avenue, Boston, 02115, Massachusetts, USA

    Amalia M. Issa

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  1. Amalia M. Issa
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Related links

Related links

DATABASES

LocusLink

ALOX5

APOE

CETP

CYP2C19

CYP2D6

β-fibrinogen

5-HT2A receptor

lipoprotein lipase

α2-macroglobulin

Medscape DrugInfo

amoxicillin

clozapine

montelukast

omeprazole

pravastatin

tacrine

zileuton

OMIM

Alzheimer's disease

schizophrenia

FURTHER INFORMATION

The Drug Information Association's Pharmacogenetics Working Group

FDA

Human Genome Project

InPharm

International Communication Forum in Human Molecular Genetics

National Center for Biotechnology Information dbSNP database

NIH–NIGMS Pharmacogenetics Research Network

Office for Human Research Protections

Office of Orphan Products Development

Pharmaceutical Research and Manufacturers of America

The Pharmacogenetics Knowledge Base

The SNP Consortium

Stanford Genomic Resources

LINKS

Nature Genetics

Glossary

GENETIC POLYMORPHISM

The difference in DNA sequence among individuals, groups or populations. Genetic variations that occur in more than 1% of a population would be considered useful polymorphisms for genetic-linkage analysis.

GENOTYPE

The genetic constitution of an organism, as distinguished from its physical appearance or characteristics (its phenotype).

GENOTYPING

The determination of relevant nucleotide base sequences in each of the two parental chromosomes.

PHENOTYPE

The physical characteristics of an organism or the presence of a disease that might or might not be genetic.

ALLELE

An alternative form of a genetic locus — a single allele for each locus is inherited from each parent.

SINGLE-NUCLEOTIDE POLYMORPHISM

(SNP). The DNA sequence variations that occur when a single nucleotide (A, T, C or G) in the genome sequence is altered.

PENETRANCE

The probability of a gene or genetic trait being expressed. 'Complete' penetrance means that the gene or genes for a trait are expressed in all the population who have the genes. 'Incomplete' penetrance means that the genetic trait is expressed in only part of the population.

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Issa, A. Ethical perspectives on pharmacogenomic profiling in the drug development process. Nat Rev Drug Discov 1, 300–308 (2002). https://doi.org/10.1038/nrd771

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