Agreement Statistics for Methods Comparison Based on Total Error Per CLSI EP46 and FDA Assay Criteria Using Web Tool

BACKGROUND: Per CLSI EP46 (2025), the validation of a test device, when compared to a reference device, should focus on evaluating the total analytical error (TAE) and show that it is within an allowable total error (ATE). Specifically, FDA Assay criteria (2013) suggest that 95% of test device data should be within ATE from those of a reference device. This article presents statistical tools for assessing agreement in method comparisons and assay validations that satisfy the above guidance. Here, we emphasize the concept and provide examples using a web tool. METHODS: The validated web tool, free for public use, is available to satisfy the above hard-defined criteria for device acceptance and provides information regarding accuracy and precision. We use test and reference measurements of selected clinical chemistry and hematology analytes as examples. We selected 4 analyte cases to evaluate: precise and accurate, precise and inaccurate, imprecise and accurate, and imprecise and inaccurate. RESULTS: Among the 4 analytes, the precise and accurate case is the only one that passed the FDA Assay criteria. We also present the misleading results indicated by traditional paired t-test and regression analyses, which rejected the case that passed the FDA Assay criteria. CONCLUSIONS: The freely accessible and validated web tool successfully identifies analytes that meet the FDA Assay criteria and provides an indication of when an investigation of a potential precision and/or accuracy problem is required.