Scientific Challenges and Implementation Barriers to Translation of Pharmacogenomics in Clinical Practice

Abstract

The mapping of the human genome and subsequent advancements in genetic technology had provided clinicians and scientists an understanding of the genetic basis of altered drug pharmacokinetics and pharmacodynamics, as well as some examples of applying genomic data in clinical practice. This has raised the public expectation that predicting patients' responses to drug therapy is now possible in every therapeutic area, and personalized drug therapy would come sooner than later. However, debate continues among most stakeholders involved in drug development and clinical decision-making on whether pharmacogenomic biomarkers should be used in patient assessment, as well as when and in whom to use the biomarker-based diagnostic tests. Currently, most would agree that achieving the goal of personalized therapy remains years, if not decades, away. Realistic application of genomic findings and technologies in clinical practice and drug development require addressing multiple logistics and challenges that go beyond discovery of gene variants and/or completion of prospective controlled clinical trials. The goal of personalized medicine can only be achieved when all stakeholders in the field work together, with willingness to accept occasional paradigm change in their current approach.

A physiome interoperability roadmap for personalized drug development

“…The term, both in the manner of its most frequent usage and in its actual clinical implementation to date, primarily refers to effects of pharmacogenomics (i.e. heritable genomic variation on drug pharmacokinetics (PK) and pharmacodynamics (PD)) and the consequent alteration of dosing regimes to minimize unwanted side effects caused by the impact of these adverse manifestations of the genotype evident at a molecular, cellular, tissue or whole-organ level [1,2].…”

Are Evidence Standards Different for Genomic‐ vs. Clinical‐Based Precision Medicine? A Quantitative Analysis of Individualized Warfarin Therapy

“…Although progress has been made in PM-related translational research, implementation in clinical practice has been slow (2, 3) primarily because of concerns about clinical evidence sufficiency and costs (4–6). Evidence thresholds strongly influence the time required for a new technology to move from research to practice(7).…”

Feasibility of clinical pharmacist-led CYP2C19 genotyping for patients receiving non-emergent cardiac catheterization in an integrated health system

“…Despite existing data associating variant CYP2C19 genotypes with altered metabolizing enzyme phenotypes, clinical implementation of genotyping is not routine. The dearth of routine genotyping may be due to barriers such as cost of genetic testing, delayed availability of test results, lack of supportive infrastructure (e.g., clinical decision support tools within electronic health records), educational gaps in knowledge of testing and interpretation of results among front-line clinicians, and in the case of clopidogrel in particular, lack of endorsement by the American College of Cardiology/American Heart Association citing the absence of published randomized controlled trials demonstrating that genotyping improves clinical outcomes 6,7,8,9,10,11,12…”