Pharmacogenomic Biomarkers of Susceptibility to Adverse Drug Reactions: Just Around the Corner or Pie in the Sky?

Mark I. Avigan


Personalized Medicine. 2009;6(1):67-78. 

In This Article

Steps in the Development & Utilization of Genomic Biomarkers for ADRs

Necessary steps in the pathway for development and utilization of pharmacogenomic biomarkers for ADRs begin with observation of ADRs in subsets of patients exposed to a certain drug, and continue with the performance of exploratory and replication studies that seek to identify and qualify biomarkers associated with these adverse events. In the study phase it is important to measure the sensitivity, specificity and predictive values of these markers. These steps are followed by the review and critique of all pertinent data by academics and regulators to establish the groundwork for their implementation as risk-management tools. An essential function in this phased process is effective communication with all appropriate stakeholders, including healthcare providers in order to gain feedback and enhance acceptance of newly developed biomarkers by the clinical community. A combined US National Cancer Institute-National Human Genome Research Institute (NCI-NHGRI) Working Group has recently developed a list of criteria that should be used to evaluate results that demonstrate a genotype-phenotype association, both in discovery and replication studies.[10] In addition, the working group has emphasized the importance of publication of both positive and negative association study results. Finally, it is important to perform studies to evaluate the effectiveness of pharmacogenomic biomarker testing in a real-world setting.

When results of a pharmacogenomic test(s) provide significant value in forming a treatment decision, either to contraindicate usage or make an adjustment in dosaging of a drug or biologic agent, product labeling should be modified to reflect these findings and appropriately instruct healthcare providers regarding the utility of testing. There are a growing number of examples of pharmacogenomic tests that have been developed that add important value to the clinician's armamentarium of tools for managing drug treatment-related risk. Not surprisingly, since 1985 there has been a dramatic rise in the number of newly approved drugs by the US FDA that contain pharmacogenomic information.[11,102] So far, of the product labels that refer to genomic biomarkers, a majority pertain to polymorphisms in cytochrome P450 isoenzymes. Testing for these typically is performed to inform optimal dosing.