Comparative Pathologists: Ultimate Control Freaks Seeking Validation!

Abstract

Definable, reproducible, and meaningful are elemental features of grading/scoring systems, while thoroughness, accuracy, and consistency are quality indicators of pathology reports. The expertise of pathologists is significantly underutilized when it is limited to rendering diagnoses. The opportunity to provide guidance on animal model development, experimental design, optimal sample collection, and data interpretation not only contributes to job satisfaction but also, more importantly, promotes validation of the pathology data. Keys to validation include standard operating procedures, experimental controls, and standardized nomenclature applied throughout the experimental design and execution, tissue sampling, and slide preparation, as well as the creation or adaptation and application of semiquantitative grading/scoring systems. Diagnostic drift, thresholds, mental noise, and various diurnal fluctuations strongly influence the repeatability of grading/scoring systems used by the same or different pathologists. Quantitative image analyses are not plagued by the visual and cognitive traps that affect manual semiquantitative grading schemes but may still be affected by technical variables associated with necropsy, tissue sampling, and slide preparation. The validity of a grading scheme is ultimately assessed by its repeatability and biologic relevance, so it is important to correlate scores with comprehensive pathobiology data such as results of antemortem imaging, clinical pathology data, body and organ weights, and histopathologic evaluation of full tissue sets.

Chlamydia pecorum–Induced Arthritis in Experimentally and Naturally Infected Sheep

“…16,28,34 After the designation of inflammatory features, it was important to avoid extreme ranges of severity levels 42 to create an adaptive, reproducible, and easily applicable scoring system that started with an unblinded initial evaluation, followed by a targeted masked review. 31 The inflammatory features were determined (1) on the basis of standard definitions for chronic and active inflammation under the supervision of a dipl. ECVP pathologist and (2) based on the comparison of synovial pathologic features to normal synovial tissue as previously assessed for human rheumatology research.…”

“…All tissue assessments were performed according to the targeted masked review, as previously described. 31…”

“…All tissue assessments were performed according to the targeted masked review, as previously described. 31 Immunohistochemistry Immunohistochemistry (IHC) to detect chlamydial antigen in tissues of joints and internal organs of experimentally infected, naturally infected and control animals was performed as previously described. 21 A total of 312 FFPE tissues were examined using a light microscope at a magnification of 100Â and 400Â.…”

Scientific and Regulatory Policy Committee Best Practices: Recommended (“Best”) Practices for Informed (Non-blinded) Versus Masked (Blinded) Microscopic Evaluation in Animal Toxicity Studies

“…37,38,41,46,47 The unavoidable, marginal diagnostic variation among pathologists is inherent to the nature of all medical judgments and is inconsequential to overall interpretation of microscopic data. 2,13,41,48…”

Observational Study Design in Veterinary Pathology, Part 2: Methodology

“…Furthermore, systematic errors that differ between the study groups may cause differential information bias that could lead to a spurious outcome of the study. Guidelines for histologic scoring and grading have been published 16,23,30,32,45 including a series in Veterinary Pathology on scoring histologic lesions in comparative pathology research, 22,24,25,31,52 and guidelines and insights on cancer grading studies are also available. 29,55…”