Model‐Informed Reverse and Forward Translation of Safety Risks in Drug Development

: Despite major scientific investments, safety accounts for significant pipeline attrition, especially in late preclinical and early clinical development. Many failures are due to difficulty interpreting safety signals or difficulty optimizing schedules of compounds with narrow therapeutic margins. Model-informed translation can address these challenges, both through "forward" translation of early signals to future scenarios, as well as through "reverse" translation of safety data into mechanistic insight.