The “Crisis of Reproducibility” of Animal Studies: Causes and Solutions

Abstract

Abstract A majority of post-phase III clinical trial therapies have historically failed to receive regulatory approval due to a lack of demonstrated efficacy. According to a 2012 study published by Amgen researchers, 90% of the 50+ in vivo oncology studies were irreproducible. Over the last two years, questions and debates concerning the validity of the preclinical science data have resulted in multiple published reviews. Suboptimal disease models, inadequate or inappropriate controls, and poor documentation practices (including electronic spreadsheets) will be discussed as primary causes of irreproducibility in animal research. To address these concerns, several best-practice resources and initiatives have been made available to the research community. The ARRIVE guidelines, PHISPS protocols, and the N3R Design Assistant will be described as practically-applicable concepts and publicly-available resources to address issues contributing to the “Crisis of Reproducibility”. Researchers have increasingly adopted animal study workflow software applications and databases, which were developed to address this crisis. By applying such automated and time-saving technologies, researchers can now more easily standardize the highly variable but detailed processes of study design, procedure adherence and descriptions, animal welfare parameter monitoring, graphing, data analyses, report creation, task and measurement scheduling, and data preservation. Using some real-life examples, the advantages and disadvantages of preclinical study software applications and the use of electronic spreadsheets will be discussed in the context of helping to resolve the “Crisis of Reproducibility” in animal studies.