Liver safety assessment: required data elements and best practices for data collection and standardization in clinical trials.

A workshop was convened to discuss best practices for the assessment of drug-induced liver injury (DILI) in clinical trials. In a breakout session, workshop attendees discussed necessary data elements and standards for the accurate measurement of DILI risk associated with new therapeutic agents in clinical trials. There was agreement that in order to achieve this goal the systematic acquisition of protocol-specified clinical measures and lab specimens from all study subjects is crucial. In addition, standard DILI terms that address the diverse clinical and pathologic signatures of DILI were considered essential. There was a strong consensus that clinical and lab analyses necessary for the evaluation of cases of acute liver injury should be consistent with the US Food and Drug Administration (FDA) guidance on pre-marketing risk assessment of DILI in clinical trials issued in 2009. A recommendation that liver injury case review and management be guided by clinicians with hepatologic expertise was made. Of note, there was agreement that emerging DILI signals should prompt the systematic collection of candidate pharmacogenomic, proteomic and/or metabonomic biomarkers from all study subjects. The use of emerging standardized clinical terminology, CRFs and graphic tools for data review to enable harmonization across clinical trials was strongly encouraged. Many of the recommendations made in the breakout session are in alignment with those made in the other parallel sessions on methodology to assess clinical liver safety data, causality assessment for suspected DILI, and liver safety assessment in special populations (hepatitis B, C, and oncology trials). Nonetheless, a few outstanding issues remain for future consideration.

Lääkeainemetabolian merkitys lääkekehittelyssä : lajierot ja ennustamisen vaikeus

Translationaalinen lääketutkimus ja -kehitys.

Biomarkers - regulatory and toxicological perspectives

Referaatti kongressiesitelmästä.

The human placental proteome is affected by maternal smoking

Acknowledgements This paper belongs to the studies carried out by Kuopio Birth Cohort consortium (www.KuBiCo.fi). We thank Ms Pirjo Hänninen for expert laboratory assistance at University of Eastern Finland, Ms Margaret Fraser, Dr Panagiotis Filis and the Proteomics Core Facility at the University of Aberdeen for their expert assistance. We also thank the staff of the Department of Obstetrics and Gynaecology in Kuopio University Hospital for skilful collection of these specimens. This work was supported by the Academy of Finland [122859/2007], the Helena Vuorenmies Foundation, the Emil Aaltonen Foundation, the University of Eastern Finland Doctoral Programme in Drug Research and the Medical Research Council, UK [MR/L010011/1]. The funders played no roles in study design, data collection, data analysis, manuscript preparation and/or publication decisions.

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