Assessment of clinical performance without adequate analytical validation: A prescription for confusion

Objectives: 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.