A Pathology Working Group (PWG) is a specialized type of review composed of a group of expert pathologists convened to answer specific questions and provide an independent unbiased opinion regarding study results. They may be convened by study sponsors, consortiums, or government agencies. Members of the PWG may come from academia, government, or industry and are selected based on their experience in toxicologic pathology, as well as their expertise in the particular area being discussed.
PWGs are generally conducted after a study (or studies) have been finalized, and thus require full documentation. PWGs are often convened to discuss tumor endpoints (diagnostic criteria for different tumor types and the impact of this on relationship to treatment). They can also be convened to discuss the incidence and severity of non-neoplastic findings. PWGs for non-neoplastic findings are often initiated when studies have been evaluated at several different institutions, when there is a lack of clarity regarding diagnostic criteria or consistency in severity grading, or to address questions that are raised by regulatory authorities. Although PWGs are most often focused on a single change, in some instances, all target organs in a study are examined.
Pathology Working Groups may be convened to answer any number of specific questions. Here are some possible situations where a PWG might be useful:
• Studies with final reports
• Pivotal studies with controversial endpoints
• To address questions that are of concern by regulatory agencies
• Comparison of results of multiple studies that may have been conducted and evaluated by different laboratories and/or pathologists
• Mediation of important discrepancies between study and reviewing pathologists
PWGs have been conducted by EPL to:
• Confirm the incidence of neoplasms occurring in a target organ tissue in oncogenicity studies (kidney, liver, etc.)
• Compare the incidence of proliferative liver lesions in multiple studies conducted with several related compounds
• Compare the incidence and severity of lesions from target organs in animals given the same test article in different CROs and evaluated by different pathologists
PWGs generally consist of five voting members and a non-voting PWG chairperson who chairs the session, and coordinates and prepares the data for the PWG. After the slides have been coded by the chairperson, the PWG examines the slides without knowledge of treatment group or previous diagnoses. PWG members are each provided with a microscope, so that they may examine the slides individually. The final PWG diagnosis for each slide represents the majority vote of the panel members. After the PWG has examined all the slides and discussed the findings, the chairperson prepares a draft report of the PWG’s findings, interpretation, and conclusions for the panel to discuss and edit.
The PWG does not review an entire study – members’ deliberations are limited to the specific question or questions for which the panel was convened. In many cases, a complete peer review is conducted prior to the PWG. This may be a routine peer review of the study, or it might be a targeted review conducted specifically for the PWG.
PWGs are not a routine part of the quality review of a study, but they are extremely helpful to answer specific questions regarding diagnoses or interpretations for a study. The results from an independent panel of experts often carry a great deal of weight with regulatory agencies, and have helped to resolve seemingly difficult situations on many occasions.