Bridging the Divide Between Pre-Clinical and Clinical Drug Safety

The goals of this new Gordon Research Conference are to stimulate discussion of contemporary approaches to assessing drug safety, and to bridge the divide that exists between individuals working in pre-clinical and clinical drug safety research. The speakers, discussion leaders, and attendees will include a mix of scientists from academia and Pharma/biotech. An important benefit of the design of this conference is the blend of innovation in the lab and its translation in the clinic. Scientific sessions are sequenced in a way that parallels the drug development process itself, building momentum from the molecular to the epidemiological, as follows:

• Chemical Biology and Systems Toxicology: The opening sessions features a Keynote address on Bioengineering Systems Analysis of Drug Reactions by Doug Lauffenburger (MIT) followed by presentations in the session Chemical Biology: Merging Computational Chemistry and Systems Biology by Jeremy Jenkins (Novartis), Michael Keiser (Seachange Pharma & UCSF), and Jeff Sutherland (Lilly). Key topics include computational modeling and knowledge management approaches to leveraging the growing wealth of information in the public domain for early safety assessments of drug targets, pathways, and the compounds that modulate them.
• Stem Cell and 3D Biology In Vitro: Presentation by Kit Parker (Wyss Institute, Harvard), Uwe Marx (Technische Universitat, Munich), Teresa Woodruff Northwestern University), Ed LeCluyse (The Hamner Institutes), and novel applications in Pharma by Matt Peters (AstraZeneca) focus on applications of primary cells, stem cells, 3D cell culture (microphysiologic) models including their utility in exploring toxicities that occur at the tissue level in animals and humans.
• Animal Models and the Future of Drug Safety Testing: The third set of sessions focus on the value of animal models, and applications of preclinical and clinical biomarkers of human toxicities, with focus on the heart, liver, and kidney. Content for this part of the program is richly elaborated by leading scientists including Jim Stevens (Eli Lilly), Jill Steidl-Nichols (Pfizer), Thomas Hartung (Johns Hopkins University), Richard Knight (AstraZeneca), Husam Younis (ISIS), and Darrell Abernethy (FDA).
• Human Safety in Development and Post-Approval: The final sessions focus on application of novel biomarkers of drug toxicity by Vishal Vaidya (Harvard) and Stephen Furlong (AstraZeneca), Pharmacoepidemiology and drug safety in late-phase development including identification of emerging drug safety issues post-approval by Israel Guttierez (Exelixis), Abraham Hartzema (University of Florida), and Bill DuMouchel (Oracle Health Sciences). The conference closes Thursday evening with a presentation entitled "Bench to Bedside 10 Years On: Predicting Risk to Improve Drug Safety" by Trevor Gibbs (London School of Hygiene and Tropical Medicine).

We look forward to talks and robust discussions that explore both basic and applied research questions such as these: What are the most important drug safety issues for which we need additional research and technologies? What technological approaches have been effective, for what applications, which have been less successful, and why? For which drug safety issues are animals successful predictors of human drug safety issues, and for which are they inadequate? Are human stem cells superior nonclinical models for predicting human drug safety, for which types of toxicity, and why? What are the risk factors that predispose humans to adverse drug reactions? What do we currently know, and what do we suspect, are the contributions of genetic polymorphisms to drug safety issues in humans? How could this knowledge improve the design of clinical trials and guide the safe use of marketed compounds?