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Pathogenesys strongly believes that adequate assay validation is a critical part of providing testing services during the conduct of a clinical trial. Pathogenesys will provide evidence of adequate test validity in the form of a validation report prior to reporting results for each test performed.
CLIA and GLP regulations require that the performance characteristic for all Immunohistochemical tests be assessed with narrow criteria for adequacy defined. To this end, Pathogenesys performs testing and documents adequacy of the Sensitivity, Specificity and Precision of each test. However, validation doesn’t end there. It is not adequate to initially characterize the validity of an assay and stop there. Too often valid tests fall short of providing accurate test results. Continuing performance of every test should be monitored periodically and frequently to maintain validity. Positive and negative tissue and reagent controls are included with every test batch performed to ensure high ongoing test performance. For semi-quantitative analysis of particular analytes, additional controls that results in a range of results should also be performed, and if volume permits, the analysis of the ongoing positive rate should be assessed periodically.
Despite adequate controls, additional problems can arise. The performance of Epidermal Growth Factor Receptor Immunohistochemistry is a prime example where the diagnostic industry has fallen short in providing adequate results. Like many IHC assay, this test requires a protease to retrieve the antigen from the detrimental effects of tissue fixation with formalin prior to staining with specific antibodies. While robust, this technique can occasionally lead to over-digestion of the tumor paraffin section resulting in a disappearance of cellular membranes. Without membranes on the slide the test cannot be read adequately. To the well-trained Pathologist, extreme examples of this are not problematic, but if the over-digestion is subtle, it may present problems during slide interpretation. End users should be wary of laboratories that perform protease-mediated antigen retrieval on poorly fixed tissue. Samples sent via courier to even local laboratories, with prior adequate fixation are particularly at risk.
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