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

Histopathology data comprise a critical component of toxicology studies conducted on experimental drugs and are typically presented as finding incidence counts and severity scores per organ, tabulated in study reports. These data are oftentimes presented on multiple pages of a report which can be challenging for review and aggregation of results. However, the SEND (Standard for Exchange of Nonclinical Data; a subpart of CDISC-SDTM) standard provides a means for electronically collecting and managing histopathology data in a uniform fashion which can allow informatics systems to archive, display and analyse data in novel ways. Various software applications have become available to convert histopathology data into graphical displays as well as outputs for visual 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 (e.g. histopathology versus organ weight data) 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 involved in drug discovery and development. Graphical displays 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

Development of Pandemic Vaccines: ERVEBO Case Study

Preventative vaccines are considered one of the most cost-effective and efficient means to contain outbreaks and prevent pandemics. However, the requirements to gain licensure and manufacture a vaccine for human use are complex, costly, and time-consuming. The 2013–2016 Ebola virus disease (EVD) outbreak was the largest EVD outbreak to date and the third Public Health Emergency of International Concern in history, so to prevent a pandemic, numerous partners from the public and private sectors combined efforts and resources to develop an investigational Zaire ebolavirus (EBOV) vaccine candidate (rVSVΔG-ZEBOV-GP) as quickly as possible. The rVSVΔG-ZEBOV-GP vaccine was approved as ERVEBOTM by the European Medicines Authority (EMA) and the United States Food and Drug Administration (FDA) in December 2019 after five years of development. This review describes the development program of this EBOV vaccine, summarizes what is known about safety, immunogenicity, and efficacy, describes ongoing work in the program, and highlights learnings applicable to the development of pandemic vaccines

Projecting the impact of an ebola virus outbreak on endangered mountain gorillas.

Ebola virus is highly lethal for great apes. Estimated mortality rates up to 98% have reduced the global gorilla population by approximately one-third. As mountain gorillas (Gorilla beringei beringei) are endangered, with just over 1000 individuals remaining in the world, an outbreak could decimate the population. Simulation modeling was used to evaluate the potential impact of an Ebola virus outbreak on the mountain gorilla population of the Virunga Massif. Findings indicate that estimated contact rates among gorilla groups are high enough to allow rapid spread of Ebola, with less than 20% of the population projected to survive at 100 days post-infection of just one gorilla. Despite increasing survival with vaccination, no modeled vaccination strategy prevented widespread infection. However, the model projected that survival rates greater than 50% could be achieved by vaccinating at least half the habituated gorillas within 3 weeks of the first infectious individual