title: Non-linearity within the primary measurement range of a lipase assay as the cause of a gap in the interpatient lipase results distribution.
abstract: OBJECTIVE
  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 (300U/L) for automated repeat-on-dilution). Calculation or other errors within the automated dilution process were ruled out. Linearity of assay results was investigated.
  
  
  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 400U/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.
authors.affiliation: Department of Pathology, Jefferson University Hospitals, Philadelphia, PA, United States.
authors.forename: Ashley N
authors.initials: AN
authors.lastname: Vogel
authors.affiliation: Department of Pathology, Jefferson University Hospitals, Philadelphia, PA, United States.
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Goldsmith
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Marzinke
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Sokoll
authors.affiliation: Department of Pathology, Jefferson University Hospitals, Philadelphia, PA, United States. Electronic address: douglas.stickle@jefferson.edu.
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Stickle
mesh_terms: D006801:Humans; D008049:Lipase / Q000378:metabolism*; D015203:Reproducibility of Results
chemical_list: D008049:Lipase
keywords: Linearity; Lipase; Proficiency testing; Quality assurance