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

• The interpatient lipase results distribution showed a distinct gap (Roche Cobas assay).
• The gap occurred above the upper limit of the assay's primary measurement range.
• The assay was found to be nonlinear in the primary measurement range.
• A range of assay results (the observed gap) were unattainable due to nonlinearity.
• CAP linearity survey results for this assay did not identify this form of nonlinearity.

ObjectivesInterpatient 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 methodsLinearity of experimental sample dilution series data was assessed by correlation coefficient, intercept, and constancy of slope.ResultsDilution 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.ConclusionsNon-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.