Steven I. Gutman, MD, director of the FDA’s Office of In Vitro Diagnostic Device Evaluation and Safety, on how laboratories should validate a hsCRP test for cardiac use:
“Although this FDA guidance is not intended for laboratory practice or for compliance with CLIA requirements, it could be used to provide a general framework for how to demonstrate clinical effectiveness of the assay in their hands.”
“Since different assays may generate noncongruent values, the importance of validation is to provide information so that when a clinician receives a report he or she will know how to properly risk stratify the patient.”
“One mechanism is to repeat the clinical study that was used to show how the hsCRP number contributes to risk. This is clearly not reasonable for the average lab.”
“Another is to create a strong analytical bond between a test studied with clinical end points and the test not clinically studied in a manner to ensure that the information generated does not misclassify patients.”
“CLIA allows considerable flexibility in how this is done, but the patient benefits if this is done well and the signal is strongly linked to established outcomes. So the lab must demonstrate that the numbers it generates are statistically and clinically equivalent to the numbers for a well-studied test. A reasonable technique might be to assess total error for the test in question compared to a test with known clinical behavior and determine if this meets the clinical practice needs of the laboratories’ users.”
Anne Paxton is a writer in Seattle.