title: Assessment of clinical performance without adequate analytical validation: A prescription for confusion.
abstract: OBJECTIVE
  Lp-PLA2 is a biomarker with promise for predicting cardiac risk. The lack of reproducible results has limited its use. In evaluating a new reagent kit, we investigated conditions for optimal reproducibility.
  
  
  METHODS
  The Auto-PLAC reagents were evaluated on the Cobas instrument. Performance characteristics, stability, and population ranges were determined.
  
  
  RESULTS
  Analytical performance characteristics replicated manufacturer's claims. The stability profile of the analyte was unusual, with increasing results observed with storage at 4°C or -20°C. Only storage at -70°C gave acceptable stability. Population median values with properly preserved samples were much lower than the cut off previously validated for increased risk.
  
  
  CONCLUSIONS
  It is postulated that variability in specimen handling was a major contributor to the lack of traceability of the current reagents to the earlier clinical studies demonstrating its utility. We are now unsure how to identify reliable criteria for result interpretation.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Lawrence K
authors.initials: LK
authors.lastname: Oliver
authors.forename: Nikolay
authors.initials: N
authors.lastname: Voskoboev
authors.forename: Don
authors.initials: D
authors.lastname: Heser
authors.forename: Joseph P
authors.initials: JP
authors.lastname: McConnell
authors.forename: Shannon
authors.initials: S
authors.lastname: Hodel-Hanson
authors.forename: Heidi
authors.initials: H
authors.lastname: Callanan
authors.forename: Allan S
authors.initials: AS
authors.lastname: Jaffe
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000032:analysis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000175:diagnosis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011933:Reagent Kits, Diagnostic; D012016:Reference Values; D015203:Reproducibility of Results; D013048:Specimen Handling / Q000379:methods
chemical_list: D011933:Reagent Kits, Diagnostic; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase