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Table 3 Proposed stepwise validation path for Alzheimer’s disease biomarkers

From: β-Secretase1 biological markers for Alzheimer’s disease: state-of-art of validation and qualification

Parameter Definition
Robustness The ability of a method to remain unaffected by small variations in method parameters
Precision The closeness of agreement between independent test results obtained under stipulated conditions
Trueness The closeness of agreement between the average value obtained from an extensive series of test results and an accepted reference value
Uncertainty A parameter associated with the result of a measurement that characterizes the dispersion of the values could reasonably be attributed to the measurand
Limits of quantification Highest and lowest concentrations of analyte that have been demonstrated to be measurable with acceptable levels of precision and accuracy
Dilutional linearity Dilutional linearity is performed to demonstrate that a sample with a spiked concentration above the ULOQ can be diluted to a concentration within the working range and still give a reliable result
Parallelism Relative accuracy from recovery tests on the biological matrix or diluted matrix against the calibrators in a substitute matrix
Recovery The recovery of an analyte in an assay is the detector response obtained from an amount of the analyte added to and extracted from the biological matrix, compared to the detector response obtained for the true concentration of the analyte in the solvent
Selectivity The ability of the bioanalytical method to measure and differentiate the analytes in the presence of components that may be expected to be present
Sample stability The chemical stability of an analyte in a given matrix under specific conditions for given time intervals
  1. Note: A committee, within the international research framework BIOMARKAPD, recently convened to propose the ten key requirements to fulfill within a step-by-step validation process. The BIOMARKAPD project aims for the standardization of biomarker measurements for AD and Parkinson’s disease (PD), including pre-analytical and analytical procedures, assay validation, and development of reference measurement procedures (RMP) and certified reference materials (CRM) for harmonization of results across assay formats and laboratories. The table captures stepwise standard operating procedures (SOP)
  2. Table adapted from [71]