EPL, Inc. - Pathology Working Group (PWG) Services
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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 nonneoplastic 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.
Transcript of EPL, Inc. - Pathology Working Group (PWG) Services
Experimental Pathology Laboratories, Inc.
Pathology Working Groups (PWG)
What is the Purpose of a PWG?
• Independent unbiased assessment to address specific
questions concerning the study results
• The Pathology Working Group (PWG) does not review the
entire study
• Pathology peer review and data audits are used to provide a
detailed review of the study data
• PWG review limited to specific findings or toxicologic end
points
• May be convened to address questions presented by
regulatory authorities following IND or NDA submission
• May be convened to address issues that have resulted in a
clinical hold being placed on a drug in development
• May be convened establish appropriate nomenclature and
diagnostic criteria for lesions of interest
When Should a PWG Review be
Considered?
• Studies with final reports
• Pivotal studies with controversial end points
• 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
Examples of Issues Addressed During a
PWG Review
• Incidence of neoplasms occurring in a target organ tissue in oncogenicity
studies (kidney and adrenal medulla)
• Comparison of proliferative liver lesions in multiple studies conducted with
several PCB compounds to understand relative toxicity
• Comparison of heart lesions in rats given the same test article in two
different labs and evaluated by two different pathologists (cardiomyopathy
vs. degeneration/necrosis with fibrosis)
• NOAEL for alveolar macrophages with metered dose inhaler route of drug
administration
• Relevance of low incidences of neoplasms only in treated groups in 13
week toxicity studies (renal tubule tumors and malignant lymphoma)
• Misinterpretation of tissue artifacts as treatment related (“dark neurons” in
brain; formalin fixation artifact in testes)
• Human relevance of rodent neoplasms (rat kidney; mouse lung; mouse
liver)
How is the PWG Review Performed?
• PWG examines coded slides without knowledge of treatment
group or previous diagnoses
• Each panel member records his/her diagnoses on worksheets
provided by the chairperson
• Each member of the panel voices their opinion (vote) concerning
each diagnosis
• In instances where there is wide variance of opinions concerning a
diagnosis, the panel discusses the lesion and a second vote may
be necessary
• A PWG consensus diagnosis is determined for each slide
examined by majority vote
• The final consensus diagnosis of the PWG is recorded by the
PWG chairperson
• After the chairperson records the final PWG diagnoses, the results
are decoded and tabulated for evaluation
• The PWG panel evaluates the results and provides conclusions
resulting in a Final PWG Report
