Toxicologic Pathology Forum Opinion Piece: Current Use of Non-blinded vs. Blinded Histopathologic Evaluation in Animal Toxicity Studies

The Society of Toxicologic Pathology (STP) explored current institutional practices for selecting between non-blinded vs. blinded histopathologic evaluation during Good Laboratory Practice (GLP)-compliant, regulatory-type animal toxicity studies using a multi-question survey and STP-wide discussion at the 2019 STP annual meeting. Survey responses were received from 107 individuals representing 87 institutions that collectively employ 589 toxicologic pathologists. Most responses came from industry (N = 46, mainly biopharmaceutical or contract research organizations) and consultants (N = 24). For GLP-compliant animal toxicity studies, histopathologic evaluation usually involves initial (primary) non-blinded analysis, with post hoc informal blinded re-examination at the study pathologist’s discretion to confirm subtle findings or establish thresholds. Initial blinded histopathologic evaluation sometimes is elected by study pathologists to test formal hypotheses and/or by sponsors to address non-pathologist expectations about histopathology data objectivity. Current practice is that a blinded histopathologic evaluation is documented only if a formal blinding (i.e., using slides with coded labels) is employed, using simple statements without detailed methodology in the Study Protocol (or an amendment) and/or pathology report. In general, blinding is an inappropriate strategy for the histopathologic evaluation during pathology peer reviews of GLP-compliant animal toxicity studies.