Preclinical trials safety margin

An overall risk assessment should be included. This is intended to be a brief integrated summary that analyzes the preclinical and clinical data in relation to the potential risks and benefits of the proposed trial. Safety margins should be expressed on the basis of relative systemic exposure rather than applied dose. 

Once the phase 1 has been completed, next steps include the comparison of observed human exposure data (maximum concentration, Cmax and area under the concentration-time curve, AUC) to the exposures observed in the supportive preclinical studies, prediction of the human exposure in future clinical trials (based on dose level and frequency) and the calculation of the actual safety margins provided by the repeat-dose preclinical toxicology studies. The need for safety margins (based on preclinical safety and single-dose human data) to support phase lb or phase 2 dosing is usually considered on a case-by-case basis. 

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