Background

hamner watkinsThe UNC Institute for Drug Safety Sciences (IDSS) was founded in 2009, and Dr. Paul B. Watkins, a Professor of Medicine and Pharmacy at UNC, was subsequently named Director of the IDSS. Shortly thereafter, Dr. Watkins and the IDSS became involved in a project focused on developing a predictive, mathematical model of drug-induced liver injury (DILI) that eventually developed into the DILI-sim Initiative in the spring of 2011.

The DILI-sim Initiative is a consortium of pharmaceutical and other life science companies centered around and led by DILIsym Services, Inc. The DILI-sim Initiative sponsors the development and application of DILIsym®, a mechanistic model of drug induced liver injury (DILI). The goals of the DILI-sim Initiative include developing the DILIsym® software and advancing the knowledge of DILI for the benefit of the scientific community and the public at-large. DILIsym® will be used during drug development, to provide enhanced understanding of the DILI hazard posed by individual molecules, and to provide deeper insight into the mechanisms responsible for observed DILI responses at various stages of the development process.

DILIsym® allows users to carry out in vitro to in vivo extrapolation, translate preclinical results to clinical trial protocol design, and to evaluate the impact of patient variability (SimPops™) on predicted hepatotoxicity. IVIVE simulations provide a better understanding of how in vitro assay results relate to DILI responses in animals and people. In the short term, it is envisaged that results from DILIsym® will be integrated with other key nonclinical safety data and will form a part of the weight of evidence for safety assessment prior to undertaking nonclinical in vivo regulatory safety studies and progression of drug candidates into man. In the longer term, it is envisaged that use of DILIsym® will improve human risk assessment and provide enhanced opportunities for customized clinical safety monitoring during all phases of clinical development.

The development plans for DILIsym® are shaped by the DILI-sim Initiative members at regularly held meetings. Research topics are discussed, along with suggested model additions and improvements. DILI-sim engages with the Food and Drug Administration (FDA) and other academic and non-profit groups to ensure that the model includes the most recent advances related to DILI. Experiments are also undertaken at the IDSS and with collaborators as key unanswered questions related to DILI arise throughout the modeling process.

The DILI-sim Initiative is currently open to new members. Academic and non-profit researchers are also encouraged to contact the DILI-sim modeling team at DILIsym Services, Inc. to receive a copy of the DILIsym® modeling software.

Companies Supporting DILIsym® Software Development

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