Kolandaivelu K, Tzafriri AR. Lost in translational filters between peers.
Summary: In a recent issue of EuroIntervention, two articles(1)(2) and an editorial(3) detailed the translational journey taken by Qvanteq’s ultra-hydrophilic stent platform. Bench-top studies and animal experiments in two species of swine as well as rabbits suggested that a reduction in restenosis and stent thrombosis might be anticipated based on preclinical indices. In contrast, the first-in-man (FIM) study did not corroborate these results. Ultra-hydrophilic devices had a rate of neointimal formation similar to that found in contemporary bare metal stents (BMS). Rightfully, these reports question the relevance of preclinical models when ultimate risk/benefit plays out in humans with disease.
As translational researchers and authors of the preclinical animal work, we praise EuroIntervention and the Editors for curating this topic. Such timed alignment in bridging articles is rare, let alone in a single, high-impact forum. Advances in transgenic animal models4 and emerging CRISPR technologies5, coupled with the ability to correlate disease, treatment, and response in vivo with exquisite measurement tools, demand that we rethink together how best to configure the translational “filters” between animal and human. If suboptimal technologies pass, patients are exposed to undue risks. If promising technologies are sifted prematurely, putative benefits and investments are lost. Given the stakes, we feel it is crucial to comment on how divergent preclinical and clinical conclusions could have been reached. In so doing, we hope to extend hands between preclinical and clinical colleagues and advance much needed interdisciplinary, inter-sector, and international debate.