Twenty years of safety pharmacology model validation and the wider implications of this to drug discovery.

ABSTRACT

This editorial summarizes the content of the current themed issue of J Pharm Tox Methods derived from the 2019 Annual Safety Pharmacology Society (SPS) meeting held in Barcelona, Spain, and reflects on 20 years of innovation in the elaboration of methods for evaluating adversity, particularly during the nonclinical research phase. Given the success of safety pharmacology (SP) in the last 20 years, we propose that the rubric for SP method invention and validation be examined in more detail to explore whether it may have wider relevance to the drug discovery process. Articles arising from the Barcelona meeting are summarized here. They reflect current areas of controversy and innovation in SP. Not for the first time in recent years, the suitability of the No Observable Adverse Effect Level (NOAEL) as a variable in SP was considered in an article derived from a survey of SPS members. It was found from the survey and concluded from the analysis that the NOAEL is not necessary for assessing the safety of a New Chemical Entity (NCE). The meeting included scientific content from more than 190 abstracts (reproduced in the current volume of J Pharm Tox Methods). The impact of the INSPIRE program on the educational endeavor of SP, cardiovascular SP with regard to hERG and advances in CiPA and stem cells assays, the use of the echocardiogram in SP, the applicability of deep learning methods in SP and toxicology studies, the role of biomarkers in renal SP studies, and advances in CNS SP are highlighted in this issue of the Journal. This continued innovation reflects a rubric in SP that identifies problems, seeks solutions and, importantly, validates the solutions. If there is a lesson to be learned from the 20 years of annual SP methods themed issues it is that drug discovery efforts may benefit from a more rigorous validation process for discovery methods, using positive and negative controls for validation, as is done in SP method validation.