The safety of a potential drug is always onw of the main focuses during the clinical development process. For first-in-human (FIH) studies, this is particularly of concern, since there is no clinical (means in humans) data that can be relied upon. There is only the preclinical data (often called Non-clinical data) from all the animals, in silico models, etc. The combined dossier of all this preclinical data is called the Investigator's Brochure (IB). It is one of THE most important documents for a proper dose rationale. From the preclinical data, translation should be made that identifies the target organs of toxicity and safety margins for clinical trials. This information is used during the translation from the pre-clinical to the clinical phase. Reviewing safety is important to describe AND monitor adverse events that could occur and that have to be included on product labels and information leaflets. It is also used to decide on whether additional safety-focused studies should be performed (e.g. additional blood biomarker tests, slower increase in dose in ascending dose studies, more frequent monitoring of safety parameters).

The IB is often a very long (over 50, and commonly over 100 pages), difficult and 'unstructured' document. Although it has a general structure/index, data from different species, in varying units (mM, gram, etc...), and with different parameters can be found throughout the whole document. Structuring an IB to reduce the risk for an FIH-study can therefore be a solution. An example of structuring and the exact procedure including examples can be found here:

- website with general information about derisking trials by structuring the IB: here

- free online tool (registration required) for derisking an IB: here

- open access manuscript that explains in more detail the IB-derisk approach: here

- Youtube tutorial: here