The evidence gap in outcomes with pharmacogenomic testing and testing reimbursement are major challenges to pharmacogenomic implementation.
Although randomized controlled trials (RCTs) are considered the gold standard for establishing clinical utility and informing treatment guidelines, few have been done in pharmacogenomics.
Conducting an RCT for each gene-drug pair is impractical from a time and cost perspective, and more efficient approaches are needed for evidence generation.
Outcomes data with pharmacogenomic testing are emerging from pragmatic and observational studies, and further data are expected from ongoing pragmatic clinical trials.
It is expected that reimbursement will follow evidence for benefit with pharmacogenomic testing.
In his 2015 State of the Union Address, former President Obama announced the Precision Medicine Initiative signaling continued United States government support toward individualized disease detection, prevention, and management strategies
. Pharmacogenomics is one component of precision medicine and promises to optimize drug therapy through the incorporation of an individual’s genetic information in drug prescribing decisions. Genotype specifically influences pharmacokinetics and pharmacodynamics and allows for prediction of risk for adverse drug effects and likelihood of drug effectiveness.
Following decades of research into genetic determinants of drug response, pharmacogenomics is entering clinical practice at institutions across the US and Europe
. Guidelines by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and Dutch Pharmacogenetics Working Group (DPWG) have facilitated the adoption of genotype-guided therapy by informing implementation priorities and strategies
. These guidelines specifically provide recommendations for how to translate genotype results to prescribing decisions for gene-drug pairs with evidence supporting their incorporation in clinical practice.
Clinical validity is well established for gene-drug pairs addressed by the CPIC and DPGW. However, evidence supporting the clinical utility of testing is much more limited. Although randomized controlled trials (RCTs) are considered the gold standard for establishing clinical utility and informing treatment guidelines, few have been done in pharmacogenomics. Some in fact argue that RCTs should not be the level of evidentiary support required for pharmacogenomic implementation
. Rather, genotype may be viewed as one of the several patient-specific factors that influence drug response, as shown in Fig. 1 . Laboratory tests such as serum creatinine, hemoglobin, and serum potassium are routinely ordered before initiating drug therapy to guide drug and dose selection in the absence of RCT evidence to support this approach. Genotype is essentially another laboratory test that can be considered in the context of other patient-specific factors to enable individualized drug therapy. Nonetheless, demonstrating value with genotype-guided therapy is needed to influence policy makers and key stakeholders in genomic medicine, including providers and third party payers. In this article, the authors discuss existing data and ongoing efforts to generate evidence in support of genotype-guided therapy approaches and reimbursement for pharmacogenomic testing.