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