Fig. 1

Simplified illustration of a preclinical research trajectory, starting from exploration towards confirmation considering robust study design, minimum validity criteria to finally engage in a confirmatory multicenter study. At some steps a decision is required (loupe) whether to proceed with the study (check mark, blue), whether refinement of i.e., experimental design or (animal) model (question mark) is needed or whether (a priori defined) No-Go criteria were met to stop an experiment completely (red X). A robustness check after exploration should be used to decide if a within-lab replication is required before the multicenter confirmation. If minimum validity and reliability criteria are already met during exploration, a multicenter study might be planned without further in-house replication. Icons in dark blue (Generated evidence, within-lab replication, and study plan of the multicenter confirmatory study) highlight the focus areas of this review