The pharmaceutical industry’s productivity crisis is well known with >90% of drug candidates failing in clinical testing, primarily due to unexpected toxicity or lack of efficacy.  Despite advances in high throughput ‘omics technologies and the large volume of information that is now amassed on new drug candidates, the probability of success for new molecules is not improving.  Scannel and Bosney (2016) have pointed to a lack of predictive preclinical models as one of the key factors.  New approaches using human-based in vitro cell systems are showing promise for replacing the use of animal models, particularly in cases where animal testing has failed to predict human effects. These new approaches will be described along with case studies that illustrate how these methods can generate mechanistic hypotheses for drug induced cardiovascular toxicity.  Also to be discussed is how phenotypic assay data may be incorporated into safety risk assessments through the adverse outcome pathway framework being developed for chemical safety testing.

Learning Objectives: 

1. Learn about non-animal based in vitro assays for preclinical testing in drug discovery.
2. Review some of the factors that make it challenging to predict drug efficacy in clinical testing.
3. Find out about new hypotheses underlying cardiovascular disease and drug induced cardiotoxicity.