Toxicologic Pathology Forum*: Summary of the 2024 Society of Toxicologic Pathology Town Hall and 2025 STP Member Survey on Determining and Communicating Adversity.

Abstract

In 2016, the publication of the Society of Toxicologic Pathology's (STP) "best practice" recommendations on determining and communicating adversity and the European Society of Toxicologic Pathology's (ESTP) expert working group report on adversity were key milestones in addressing adversity determinations for nonclinical studies as translational tools for assessing human risk. Since then, many publications attest to the ongoing difficulty in adversity decision-making posed by unique context-specific challenges. The STP gathered input on current adversity practices from Society members via an open discussion at the 2024 STP Town Hall session (held at the STP 43rd Annual Symposium) and by a subsequent online survey. Most STP pathologists make adversity determinations by applying the STP and/or ESTP recommendations at their discretion. Adversity decisions are generally made for pivotal toxicity studies but occasionally may be assigned for other study types. Adversity determinations are difficult for certain organ systems (immune, reproductive, and endocrine) and product classes (eg, cell and gene therapies, proteins, and small molecules). Most pathologists assign adversity based on direct effects of the test article, but other factors (eg, secondary pharmacology, species relevance, adaptive responses) are also considered. Procedural adversity (eg, effects of administration/implantation) is a key factor in some circumstances.