Graphical display of histopathology data from toxicology studies for drug discovery and development: An industry perspective.

Histopathology data comprise a critical component of pharmaceutical toxicology studies and are typically presented as finding incidence counts and severity scores per organ, and tabulated on multiple pages which can be challenging for review and aggregation of results. However, the SEND (Standard for Exchange of Nonclinical Data) standard provides a means for collecting and managing histopathology data in a uniform fashion which can allow informatics systems to archive, display and analyze data in novel ways. Various software applications have become available to convert histopathology data into graphical displays for analyses. A subgroup of the FDA-PhUSE Nonclinical Working Group conducted intra-industry surveys regarding the use of graphical displays of histopathology data. Visual cues, use-cases, the value of cross-domain and cross-study visualizations, and limitations were topics for discussion in the context of the surveys. The subgroup came to the following conclusions. Graphical displays appear advantageous as a communication tool to both pathologists and non-pathologists, and provide an efficient means for communicating pathology findings to project teams. Graphics can support hypothesis-generation which could include cross-domain interactive visualizations and/-or aggregating large datasets from multiple studies to observe and/or display patterns and trends. Incorporation of the SEND standard will provide a platform by which visualization tools will be able to aggregate, select and display information from complex and disparate datasets.

Data Standardization, Pharmaceutical Drug Development, and the 3Rs.

Despite the efforts, cost, and extensive use of animals for nonclinical research, only a small number of studies have methodically compared findings from animal toxicology studies to those from human clinical trials. Impediments to understanding the translation of nonclinical safety have included the lack of easy access to data and the need for extensive data curation given the diverse terminologies, formats, and data platforms in use. SEND and SDTM study data standards, developed by CDISC and about to become mandated by FDA, can address this and other drug development issues by facilitating access to data in ways that are not currently feasible. A consistent data standard across clinical and nonclinical will discourage the development of data silos, which easily become obstacles to data sharing and maximizing the value of animal and human data. The confluence of rapid scientific advances, increasingly larger quantities of diverse data, technological advances in data mining, and the FDA's requirements for standardized study data create new opportunities for the advancement of drug development and for refinement in the way we use animals.

Community Opinions on the Collection and Use of Historical Control Data in Nonclinical Toxicity Studies.

BACKGROUND: Access and use of historical control data was identified as a top stakeholder concern across organizations according to results of a survey of needs and challenges related to nonclinical data conducted by the FDA/PhUSE Nonclinical Working Group in 2011. There is a perception there may be additional ways to capitalize on historical control data to enhance studies or submissions across industry, academia, and government. During the working sessions of the FDA/PhUSE Computational Sciences Symposium in March 2012, a Historical Control subgroup of the FDA/PhUSE Nonclinical Working Group was formed to investigate how the industry might more effectively harness the vast amount of data from untreated/vehicle control animals. The subgroup includes broad representation of stakeholders with interest in nonclinical data. METHODS: This paper describes progress to date and includes results of a second survey to determine how organizations use and would like to use historical control data. RESULTS: Respondents to the survey strongly support that historical control data are useful and should be in an accessible format. Four potential project options were posed in the survey, with an overall positive response; also, several write-in options were suggested by respondents. CONCLUSIONS: Community-supported projects to increase the availability of well-annotated and scientifically curated collections of historical control data appear to be of most interest.