Assessing Early Development Safety – Exploratory Clinical Development World 2013

patient safety clinical trials (rosmary)The afternoon session at Exploratory Clinical Development World 2013 in sunny Knightsbridge, west London, focussed in part on assessing the safety of early development. Talk included minimising clinical attrition and improving pre- to clinical safety translation, improving human translation of safety pharmacology models, and safety in FIH trials. Dr Malcolm Mitchell, Senior Medical Fellow at Eli Lilly, spoke about "Dose selection and safety in First-in-Human clinical trials". Healthy volunteers are normally default for clinical pharmacology studies, unless the risks are considered too great. However, patients are increasingly being studied for Phase I studies, especially if the disease impacts on the drug's effects. In terms of drug safety, there is a tendency to concentrate on ECGs as they are easily to monitor and it is easy to assess the QT. However, warned Dr Mitchell, is it important to look at the entire subject, including: Vital signs (e.g. BP / HR / RR / To), ECG, telemetry and AEs (e.g. rashes). The bottom line, said Dr Mitchel, was that "safety comes before science".

Dr Ignacio Rodriguez, Director, Drug Safety, Roche, spoke next on "Approaches in safety assessments of compounds with QT effects", although he expressed a wish to change his title to ‘approaches to cardiovascular safety with some emphasis on QT', for reasons that soon became clear. There is a huge emphasis around QT, and Dr Rodriguez pointed out that many speakers before him had mentioned QT.  QT prolongation has often been used as a surrogate for torsades de points (TDP), but why is there so much emphasis on QT? It's because we can, explained Dr Rodriguez. Because it's easy and cheap. However, the drug safety arena is making a move towards multichannel effects and looking at PR and QRS complexes. He also discussed ECG monitoring in Phase I and II, and why it is critical to acquire good ECG data in early development. Cardiovascular monitoring is more than QT, he explained, and ECG monitoring is more than QT.

To conclude the session on assessing early development safety, Dr Michael Merz, Chair, Liver Expert Team, Novartis, discussed "Assessing drug-induced liver injury during exploratory clinical trials". Drug-induced liver injury (DILI) is apparently the leading cause of acute liver failure in the US. Dr Merz spoke about some of the shortcomings with standard liver tests (ALT/AST/AP/yGT/bilirubin), and spoke about the use of microRNAs as human DILI biomarkers.

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