Translational safety biomarkers

Cytotoxicity Evaluated for confounding interpretation of in vitro efficacy assays, for predicting potential for human toxicity especially in liver but also if warranted by other safety assessments in bone marrow, kidney, neurons, immu-nocytes and so on. Also used for developing understanding of biochemical mechanisms of toxicity. HCA has been repeatedly demonstrated to be an effective tool in predictive toxicology. May also be used for certain translational safety biomarkers of toxicity [37]... 

Biomarkers Translational safety biomarkers (e.g., mitochondrial toxicity can be detected in vitro and in vivo), phospholipidosis [37]... 

O Brien, P.J. and Domingos, M.C. (2009) Use of high content analysis in toxicologic clinical pathology for identification and monitoring of translational safety biomarkers. American Drug Discovery... 

O Brien, P.J. (2008). Cardiac troponin is the most effective translational safety biomarker for myocardial injury in car-diotoxicity. Toxicology 245 206-18. 

O Brien, P. J. 2006. Blood cardiac troponin in toxic myocardial injury Archetype of a translational safety biomarker. Expert Reviews in Molecular Diagnosis 6 685-702. 

O Brien PJ (2014) High-content analysis in toxicology screening substances for human toxicity potential, elucidating subcellular mechanisms and in vivo use as translational safety biomarkers. Basic Clin Pharmacol Toxicol 115, 4-17. 

Matheis, K., et al., A generic operational strategy to quahfy translational safety biomarkers. Drug Discov Today, 2011.16(13-14) p. 600-8. 

A generic operational strategy to qualify translational safety biomarkers using a two-stage approach of (Jenkins et al., 2011) initial exploratory studies to identify and characterize candidate biomarkers followed by (Eosho et al., 2012) confirmatory studies to build upon the evidence of the initial studies has been described (Matheis et al., 2011). We highlight key statistical considerations in these contexts. 

STATISTICAL CONSIDERATIONS FOR EXPLORATORY CLINICAL STUDIES OF TRANSLATIONAL SAFETY BIOMARKERS... 

Matheis K, Laurie D, Andriamandroso C, Arber N, Badimon L, Benain X, Bendjama K, Clavier I, Colman P, Firat H, Goepfert J, HaU S, Joos T, Kraus S, Kretscbmer A, Merz M, Padro T, Planatscher H, Rossi A, Schneiderhan-Marra N, Schuppe-Koistinen I, Thomann P, Vidal J, Molac B (2011). A generic operational strategy to qualify translational safety biomarkers. Drug Discovery Today, 16(13) 600-608. 

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