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

Abstract

Evidence requirements for implementation of precision medicine (PM), whether informed by genomic or clinical data, are not well defined. Evidence requirements are driven by uncertainty and its attendant consequences; these aspects can be quantified by a novel technique in health economics, value of information analysis (VOI). We utilized VOI analysis to compare the evidence levels over time for warfarin dosing based on pharmacogenomic- vs. amiodarone-warfarin drug-drug interaction information. The primary outcome was the expected value of perfect information (EVPI), which is an estimate of the upper limit of the societal value of conducting future research. Over the past decade, the EVPI for the pharmacogenomic strategy decreased from $1550 to $140 vs. $1220 to $280 per patient for the drug-interaction strategy. Evidence levels thus appear to be higher for pharmacogenomic-guided vs. drug interaction-guided warfarin dosing. Clinical guidelines and reimbursement policies for warfarin PM could be informed by these findings.

Clinical Utilization of Pharmacogenetics in Psychiatry – Perspectives of Pharmacists, Genetic Counselors, Implementation Science, Clinicians, and Industry

“…There is also no clear and specific guidance on "how to evaluate a PGx test" for clinical utility in guiding treatment decisions. Various trial designs exist but due to the nature of PGx testing serving as a support tool, traditional placebo-controlled, double-blind RCT designs do not necessarily provide adequate evidence for PGx testing [47][48][49][50]. While RCTs are valuable for evaluating the clinical validity of a test (especially one with an algorithm), it does not necessarily reflect real-world usage [51].…”

How to assess pharmacogenomic tests for implementation in the NHS in England

“…Our view is that such evaluation is necessary if a test is to be adopted widely in a financially constrained healthcare system. This might mean that the evidence threshold for implementation of pharmacogenomic testing is significantly higher than for other tests that guide therapeutic decisions 28,29 . For example, dosage adjustment in impaired kidney function has often been based on theoretical pharmacokinetic calculations rather than outcome data.…”

“…This might mean that the evidence threshold for implementation of pharmacogenomic testing is significantly higher than for other tests that guide therapeutic decisions. 28,29 For example, dosage adjustment in impaired kidney function has often been based on theoretical pharmacokinetic calculations rather than outcome data. However, studies demonstrate significant unwarranted variation and excessive use of non-genetic testing, which may contribute to patient harm and escalating costs, so this approach should not be regarded as a standard of best practice.…”

Are There Different Evidence Thresholds for Genomic Versus Clinical Precision Medicine? A Value of Information-Based Framework Applied to Antiplatelet Drug Therapy

“…1 Yet there are examples of clinical PM commonly used in practice for which such data are also lacking, such as contraindication of potential drug interactions to guide pharmacotherapy. 2 Are there different evidence thresholds for genomic versus clinical PM?…”