Peer Review in Toxicologic Pathology

Abstract

Peer review of histopathology findings in safety assessment studies involving rodents and other animals is a relatively recent procedure in toxicologic pathology. It serves to ensure the integrity of the pathology evaluation in safety studies, encourages consistency of diagnostic criteria and use of common terminology, and provides a method of continuing education for participants. The use of a standardized system of pathology nomenclature and diagnostic criteria, such as the Society of Toxicologic Pathologist's Guides for Toxicologic Pathology, is of great value in the procedure. Pathology reviews may involve government-sponsored bioassay programs, in-house industrial corporations, or individual peer reviews suggested or required by government regulatory agencies. Pathology Working Groups can be an integral part of the review process. The extent of the peer review is primarily dependent on the study results; however, other variables such as confidence of the data, study size and duration, complexity, and purpose are also important considerations. Essential components of any peer review, however, include selection of tissues/lesions for review, by a reviewing pathologist, discrepancy resolution, data modification, and documentation of all aspects of the review process. Specific procedures for pathology peer review are discussed. Disagreements among pathologists discovered in peer reviews can be resolved by several methods and examples will be presented. The entire pathology peer review process should be a learning experience for all involved and can help ensure the integrity of animal toxicology studies used for important regulatory decisions involving the use of chemicals in our society.

The Effect of Chronic Progressive Nephropathy on the Incidence of Renal Tubule Cell Neoplasms in Control Male F344 Rats

“…Pathology diagnoses in NTP studies are subjected to a rigorous peer review to assure the accuracy of both neoplastic and nonneoplastic diagnoses within a study (30). Similarly, there is an effort to assure diagnostic consistency for neoplastic lesions across NTP studies.…”

The Roles of the Toxicologic Pathologist in Cancer Research

“…Pathologists also develop new applications for methods in toxicologic pathology for use in safety assessment (Cattley 2004;Cohen et al 2007;Elmore 2007;Foster 1997). Pathology peer review was initiated by the National Cancer Institute's Carcinogenesis Bioassay Program in the 1970s and advanced by the National Toxicology Program (Boorman et al 2002;Ward et al 1995). The pathology societies, the Society of Toxicologic Pathology (www .toxpath.org), the European Society of Toxicologic Pathology (www.eurotoxpath.org), the British Society of Toxicological Pathologists (www.bstp.org.uk), and the Japanese Society of Toxicologic Pathology (www.soc.nii.ac.jp/jstp3/index-e.html), among others, have provided the leadership for the nomenclature of neoplastic and nonneoplastic lesions in rodents through the development of pathology publications (Boorman et al 1990;Greaves 2007;Haschek, Wallig, and Rousseaux 2009;Maronpot 1999;Mohr 1992;Mohr et al 1996Mohr et al , 2001Ward et al 2000; Standardized System of Nomenclature and Diagnostic Criteria [SSNDC] Guides, www.toxpath.org/ssndc.asp RENI, and the new GoRENI [www.goreni.org/index.php]).…”

Regulatory Forum Opinion Piece*

“…While this practice may be expeditious in completing the peer review and reduces retained documents, it can be perceived as a ''black box'' around the peer-review process and opens the study for criticisms relative to data integrity and manipulation of data. While pathologists have long stated that peer review is intended to ensure the quality of the pathology evaluation in safety studies (Ward et al 1995;Boorman et al 2010), it does no good if the process used creates doubt in the skeptical mind of compliance and regulatory authorities relying on the final evaluation and interpretation of the data. It has previously been suggested that the peer review worksheets could be included as an appendix to the pathology report or maintained in the study file (Ward et al 1995).…”