Translation of pharmacogenomics and pharmacogenetics: a regulatory perspective - Nature Reviews Drug Discovery

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Authors and Affiliations

1. Director of the Office of Clinical Pharmacology and Biopharmaceutics, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Maryland, USA

   Lawrence J. Lesko

2. Acting Deputy Commissioner of Operations, Food and Drug Administration, 5,600 Fishers Lane, Rockville, 20857, Maryland, USA

   Janet Woodcock

Corresponding author

Correspondence to Lawrence J. Lesko.

Competing interests

The authors declare no competing financial interests.

ALLELES

Different or alternative forms of the same gene that can occupy a particular locus on a specific chromosome. Humans have two alleles at that location, one on each chromosome of a homologous pair.

AREA-UNDER-CURVE

(AUC). A metric that summarizes serum or plasma drug concentrations measured over time (for example, 24 hours) in a given individual following the administration of a drug. The AUC is interpreted as the total systemic exposure and is an index of how much of a drug reaches the bloodstream in a set period of time. AUC is also a means to compare the bioavailability of drug from a drug product.

BAYESIAN STATISTICS

A statistical method of analysis that incorporates prior knowledge (for example, on safety and efficacy parameters), specifications of prior distributions and accumulated clinical data experience into making probability calculations and designing future clinical trials.

BIOLOGIC LICENSE APPLICATION

A formal application analogous to a New Drug Application, but for biotechnology-derived pharmaceuticals (for example, complex, large molecules).

BIOMARKER

A characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacological responses to a therapeutic intervention.

HAPLOTYPE

A set or combination of alleles or linked genetic markers found on a single chromosome, which tend to be inherited together in a given individual.

INVESTIGATIONAL NEW DRUG APPLICATION

Before initiating any clinical trials of a new drug in humans, a drug sponsor must submit an Investigational New Drug application (IND) to the FDA. The IND contains three broad categories of information: data from animal pharmacology and toxicology studies, manufacturing information, and clinical protocols and investigator information.

NEW DRUG APPLICATION

A formal application that serves as a vehicle through which sponsors propose that the FDA approve a new pharmaceutical (for example, traditional small molecules) for sale and marketing in the United States. When the investigational phase of a drug is completed, the manufacturer submits the results of all the studies to the FDA in a New Drug Application (NDA) for review by FDA officials. The purpose of the NDA is for the FDA to decide if the drug meets the statutory standards for safety, effectiveness and benefit/risk for its intended use, and labelling and manufacturing quality.

NEUTROPENIA

An abnormal decrease in the number of white blood cells in the blood (as measured by an absolute neutrophil count), which increases the risk of infection and fever. It usually occurs as a result of chemotherapy.

SINGLE-NUCLEOTIDE POLYMORPHISM MAPS

A diagram or overview of a stretch of DNA containing single-nucleotide polymorphisms (SNPs). SNPs are DNA sequence variations that occur when a single nucleotide (A, T, C or G) in the genome sequence is altered in different individuals. A map of SNPs across the genome allows genetic traits to be localized by statistical association with the specific region of the genome that is marked by the SNP or multiple nearby SNPs.

Cite this article

Lesko, L., Woodcock, J. Translation of pharmacogenomics and pharmacogenetics: a regulatory perspective. Nat Rev Drug Discov 3, 763–769 (2004). https://doi.org/10.1038/nrd1499

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• Issue Date: 01 September 2004

• DOI: https://doi.org/10.1038/nrd1499