Application of a Simulation Model to Estimate Treatment Error and Clinical Risk Derived from Point-of-Care...

Area of Science:

• Clinical Chemistry
• Medical Devices
• Pharmacology

Background:

• The US Food and Drug Administration (FDA) proposed enhanced performance standards for point-of-care testing (POCT) international normalized ratio (INR) devices in 2016.
• Existing standards are based on International Organization for Standardization (ISO) 17593:2007.

Purpose of the Study:

• To estimate the frequency of warfarin dosing errors using central laboratory INR, POCT INR methods, and proposed FDA performance goals.
• To assess the impact of assay imprecision and bias on warfarin dose decisions.

Main Methods:

• A dataset of 51,912 INR results from adult patients with INR ≤4 was analyzed.
• Warfarin dose error frequency (≥1 or ≥2 dose categories) was compared between central lab and POCT methods (Roche Diagnostics CoaguChek® XS) against proposed FDA guidelines.

Main Results:

• Warfarin dose misclassification was primarily influenced by bias, with assay imprecision having minimal impact.
• Both central laboratory and POCT INR methods met the proposed FDA performance specifications.
• Equal rates of ≥2 warfarin dose category errors were observed, but statistically different rates of ≥1 error occurred in large sample sizes.

Conclusions:

• Simulation models effectively evaluate POCT INR assay performance criteria for meeting FDA guidelines.
• The Roche Diagnostics CoaguChek XS instrument demonstrated compliance with the proposed FDA performance guidelines.