4K-5
EVIDENCE THRESHOLDS AND UNCERTAINTY IN PRECISION MEDICINE: USING VALUE OF INFORMATION TO ASSESS CLINICALLY- VS GENOMICALLY-INDIVIDUALIZED CARE
Method: We developed two analogous VOI decision models for antiplatelet-treated post-MI STEMI patients receiving primary PCI, and chronologically assessed how cardiovascular risk evidence levels, drug costs, and PGx assay cost impacted the expected value of perfect information (EVPI) over time. Modeled comparators included PGx-guided therapy, concomitant clopidogrel-proton pump inhibitor therapy, and clopidogrel, prasugrel, and ticagrelor monotherapies. For clopidogrel PGx and DDI, we derived chronological estimates of the risk for major adverse cardiovascular events (MACE) from cumulative meta-analysis of observational studies specific to PCI patients. Drug costs were wholesale acquisition costs over the past 6.75 years. We assumed PGx assay costs decreased from $500 to $100 over 6.75 years. The primary outcome for both models was the EVPI per patient over 6.75 years. The secondary outcome for both models was the clinical EVPI (costs set to zero) per patient over 6.75 years.
Result: The EVPI for both the PGx and DDI decision problems were generally similar and tended to decrease over time as evidence accumulated and costs evolved, decreasing from approximately $900/patient in both analyses in 2009 to $200/patient (PGx) and $400/patient (DDI) by the end of 2015. PGx-guided antiplatelet therapy became the preferred strategy as MACE risk uncertainty decreased, while DDI became less favorable as MACE risk uncertainty decreased. There was greater simulation uncertainty (thus higher EVPI) when costs were not considered, as prasugrel (~30%) or ticagrelor (~50%) tended to provide the most net benefit after the comparatively lower cost of off-patent clopidogrel was ignored. The EVPI in both models was most impacted by: a) the 2012 expiration of clopidogrel patent protection, and b) the 2011 introduction of ticagrelor.
Conclusion: American Heart Association guidelines refrain from recommending both CYP2C19 genotyping and avoidance of proton pump inhibitors for clopidogrel patients in the absence of randomized controlled trial evidence. Conversely, clopidogrel’s FDA label recommends avoidance of both PGx and DDI drug-attenuating interactions. Our findings suggest that the evidence levels for clopidogrel PGx and DDI are similar. Chronological evidence level quantification using VOI analysis may be useful for informing pharmacogenomic testing clinical guidelines and drug labeling decisions.