Caswell Jeff L, Bassel Laura L, Rothenburger Jamie L, Gröne Andrea, Sargeant Jan M, Beck Amanda P, Ekman Stina, Gibson-Corley Katherine N, Kuiken Thijs, LaDouceur Elise E B, Meyerholz David K, Origgi Francesco C, Posthaus Horst, Priestnall Simon L, Ressel Lorenzo, Sharkey Leslie, Teixeira Leandro B C, Uchida Kazuyuki, Ward Jerrold M, Webster Joshua D, Yamate Jyoji
1 Department of Pathobiology, University of Guelph, Guelph, ON, Canada.
2 Department of Ecosystem and Public Health; Canadian Wildlife Health Cooperative (Alberta), Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada.
Vet Pathol. 2018 Nov;55(6):774-785. doi: 10.1177/0300985818798121. Epub 2018 Sep 18.
Observational studies are a basis for much of our knowledge of veterinary pathology, yet considerations for conducting pathology-based observational studies are not readily available. In part 1 of this series, we offered advice on planning and carrying out an observational study. Part 2 of the series focuses on methodology. Our general recommendations are to consider using already-validated methods, published guidelines, data from primary sources, and quantitative analyses. We discuss 3 common methods in pathology research-histopathologic scoring, immunohistochemistry, and polymerase chain reaction-to illustrate principles of method validation. Some aspects of quality control include use of clear objective grading criteria, validation of key reagents, assessing sample quality, determining specificity and sensitivity, use of technical and biologic negative and positive controls, blinding of investigators, approaches to minimizing operator-dependent variation, measuring technical variation, and consistency in analysis of the different study groups. We close by discussing approaches to increasing the rigor of observational studies by corroborating results with complementary methods, using sufficiently large numbers of study subjects, consideration of the data in light of similar published studies, replicating the results in a second study population, and critical analysis of the study findings.
观察性研究是我们许多兽医病理学知识的基础，但关于开展基于病理学的观察性研究的考量却并不容易获得。在本系列的第1部分中，我们提供了关于规划和开展观察性研究的建议。本系列的第2部分聚焦于方法学。我们的总体建议是考虑使用已经验证的方法、已发布的指南、来自原始资料的数据以及定量分析。我们讨论病理学研究中的3种常用方法——组织病理学评分、免疫组织化学和聚合酶链反应——以阐明方法验证的原则。质量控制的一些方面包括使用明确的客观分级标准、关键试剂的验证、样本质量评估、确定特异性和敏感性、使用技术和生物学阴性及阳性对照、研究者设盲、尽量减少操作者依赖性变异的方法、测量技术变异以及不同研究组分析的一致性。我们最后讨论通过用互补方法确证结果、使用足够数量的研究对象、根据类似已发表研究考虑数据、在第二个研究人群中重复结果以及对研究结果进行批判性分析来提高观察性研究严谨性的方法。
