Overview and considerations for the reporting of clinical pathology interpretations in nonclinical toxicology studies

Abstract

| INTRODUC TI ONAccurate, informative, and integrated reporting of toxicologic clinical pathology results has become a fundamental expectation in contemporary drug safety submission packages. The approach to clinical pathology reporting has historically been quite diverse due to the wide spectrum of individuals and organizations tasked with clinical pathology interpretations and generating reports, and the lack of specific regulatory guidance on reporting standards. The purpose of this manuscript is to present an overview of current clinical pathology reporting practices within the drug development industry, as well as to provide a framework that will help authors draft meaningful clinical pathology interpretive reports in support of nonclinical toxicology studies. The suggestions provided are neither intended to be prescriptive nor to constrain report authors to follow a rigid, standardized structure. Reporting practices should be appropriately adjusted according to organizational standards, study design, and results of each study. By using these principles, the clinical pathology report can serve as an essential asset in support of nonclinical safety studies, and not become just a data dump of statistically significant differences or values that fall outside of historical control ranges. | COMP ONENTS OF A CLINIC AL PATHOLOGY REP ORTEffective communication of clinical pathology findings can be performed in a variety of ways, including (a) a stand-alone clinical pathology subreport, (b) an integrated anatomic and clinical pathology report, or (c) incorporation of clinical pathology results into the main study (toxicology) report. Because there is no formal regulatory guidance specifically addressing clinical pathology reporting Abstract Clinical pathology reporting practices are diverse among individuals and organizations involved in nonclinical toxicology studies. Clear, informative, and consistent reporting of clinical pathology results increases their value and avoids misinterpretation, resulting in decreased drug development costs. In recent years, certain common practices in clinical pathology reporting have been embraced by industry leaders and more consistently utilized across the pharmaceutical industry. The purpose of this manuscript is to review current clinical pathology reporting practices and to provide nonbinding suggestions to improve consistency, quality, and value of clinical pathology reports generated in support of nonclinical toxicology studies. K E Y W O R D S clinical pathology, interpretation, nonclinical studies, reporting, toxicology

Selected Aspects of Ocular Toxicity Studies With a Focus on High-Quality Pathology Reports: A Pathology/Toxicology Consultant’s Perspective

“…In the author's experience, publications for best practices for anatomic pathology and clinical pathology reports 98,128 are useful for ophthalmology reports. The inclusion of specific elements, formatting, and arrangement of ophthalmology reports varies depending on the CRO and individual study circumstances and usually minimally contains study design, results, and discussion of standard and specialized ophthalmic examination techniques presented in Table 2, scoring schemes, and individual and summary tables of ophthalmology data.…”

Interpretative considerations for clinical pathology findings in nonclinical toxicology studies

“…For a complete review of concepts related to the determination of adversity of clinical pathology findings in nonclinical toxicology studies, readers are referred to the following publications . This section briefly covers some key concepts as related to adversity and the reporting of clinical pathology effects.…”

“…Most effects identified in a nonclinical toxicology study should generally have some indication of severity using one or both of these approaches. More detailed information on suggested approaches for the use of qualitative and/or quantitative descriptors have been presented elsewhere …”

“…The most common non‐TAR influences that have to potential to result in effects substantial enough to warrant specific mention include those related to restraint, serial blood collection (particularly in large animals), surgical manipulation, anesthesia, growth and maturation (longer duration dog and rat studies), CO 2 inhalation, and intravenous fluid administration/dilutional effects. When significant procedure‐related effects are seen in large animal studies (ie, those with pretest collections), it is often appropriate to make comparisons directly to controls as they will have similar influences on clinical pathology endpoints …”

VCP Special Report: Updates from the Regulatory Affairs Committee on the reporting and interpretation of clinical pathology in nonclinical toxicology studies

“…The current issue of Veterinary Clinical Pathology contains two ASVCP Special Reports entitled, “Interpretative considerations for clinical pathology findings in nonclinical toxicology studies” and “Overview and considerations for the reporting of clinical pathology interpretations in nonclinical toxicology studies,” devoted to reviewing contemporary practices of reporting and interpreting clinical pathology findings within nonclinical toxicology studies. It was the intent of the Regulatory Affairs Committee to create these manuscripts with authors from diverse backgrounds that could provide a well‐balanced perspective from both pharmaceutical and contract research organizations (CRO) since a broad spectrum of approaches is encountered to report clinical pathology findings in the current pharmaceutical development environment.…”