Non-linearity within the primary measurement range of a lipase assay as the cause of a gap in the interpatient lipase results distribution

Objectives: Interpatient distribution data for lipase (Roche Cobas® assay) showed an unexpected data gap, where no results were reported. This gap occurred beginning at a point just above the assay's primary measurement range (i.e., above the cutoff (300 U/L) for automated repeat-on-dilution). Calculation or other errors within the automated dilution process were ruled out. Linearity of assay results was investigated. Design and methods: Linearity of experimental sample dilution series data was assessed by correlation coefficient, intercept, and constancy of slope. Results: Dilution experiment data demonstrated a discontinuity of results between 300 and 400 U/L consistent with the observed gap in patient data. Although data within the presumed linear range of the assay had a high linear correlation coefficient (r2 > 0.99), a non-zero intercept and progressively variable slope were inconsistent with linearity. Although the assay was assessed as linear by the College of American Pathology linearity survey, survey data also demonstrated non-linearity for this assay when analyzed for slopes and intercept. Conclusions: Non-linearity in the presumed linear range of an assay can produce gaps in patient data above a repeat-on-dilution cutoff. As in this instance, CAP linearity surveys may not identify certain forms of non-linearity.