In this paper, we discuss the diagnosis of particle-induced failures in harsh environments such as space and high-energy physics. To address these effects, simulation-before-test and simulation-after-test can be the key points in choosing which radiation hardening by design (RHBD) techniques can be implemented to mitigate or prevent failures. Despite the fact that total ionising dose (TID) has slow but destructive effects overtime on silicon devices, single-event effect (SEE) impulsively disrupts the typical operation of a circuit with temporary or permanent effects. The recently released SpaceFibre protocol drives the current requirements for space applications, and the future upgrade of the LHC experiment scheduled by CERN will require a redesign of the electronic front-end to sustain a radiation level up to the 1 Grad TID level. The effects that these two environments have on two different architectures for high-radiation and high-frequency data transmission are reported, and the efficiency of the mitigation techniques implemented, based on simulations and measurement tests, in the commercial 65 nm technology, are exploited.