Diagnostic Accuracy in Fit-for-Purpose PD-L1 Testing

摘要

PD-L1 testing by immunohistochemistry (IHC) has had, and continues to have, significant impact on determining patient eligibility for specific immunotherapy drugs targeting the PD-1/PD-L1 checkpoint. CIQC proficiency testing (PT) for PD-L1 as a predictive biomarker was initiated with an aim to support Canadian laboratories with information on the quality of predictive testing for PD-L1 status in NSCLC and possibly other tumors as new indications for the testing evolve. The scope of the CIQC PT for PD-L1 testing was to compare the results of testing performed by participating laboratories (CIQC member laboratories) with the current "gold standard'Vreference standard results. Diagnostic accuracy, as described by the STARD statement,1 is particularly pertinent to PT for predictive biomarkers where demonstration that a participant laboratory's testing protocol generates results with high diagnostic accuracy, as compared to that of a designated gold standard/ reference testing protocol, on the same set of samples *being scored by the same readers using the same readout criteria. Similarly, in 2008, the Clinical Laboratory Standards Institute (CLSI) EP12-AE Approved Guideline recommends calculation of sensitivity and specificity for determination of qualitative assay performance in which a "candidate test" is compared against a "comparator test."2 Although this approach is not traditionally employed for PT, the development of precision medicine with the ever-increasing expectation of high accuracy in predictive biomarker testing as well as the increasing expectation of clinical laboratories that materials used for PT runs should contribute to the validation of their biomarker assays, both exert pressure on PT programs to adopt new models of testing that are "fit-for-t>urDose."