When Enough Is Enough: Decision Criteria for Moving a Known Drug into Clinical Testing for a New Indication in the Absence of Preclinical Efficacy Data

Abstract

Many animal models of disease are suboptimal in their representation of human diseases and lack of predictive power in the success of pivotal human trials. In the context of repurposing drugs with known human safety, it is sometimes appropriate to conduct the "last experiment first," that is, progressing directly to human investigations. However, there are not accepted criteria for when to proceed straight to humans to test a new indication. We propose a specific set of criteria to guide the decision-making around when to initiate human proof of principle without preclinical efficacy studies in animal models. This approach could accelerate the transition of novel therapeutic approaches to human applications.

Keywords: animal models; drug repurposing; translational research.

Fig. 1.

Depiction of the relative value of murine versus human testing in granulomatosis with polyangiitis, based on model developed by Little et al.