Found in translation
Lost or found in translation? Stroke is a major cause of global morbidity and mortality, yet therapeutic options are very limited. Numerous preclinical studies promised highly effective novel treatments, none of which have made it into practice despite a plethora of clinical trials. This failure to bridge the gap between bench and bedside deeply frustrates researchers, clinicians, the pharmaceutical industry, and patients. Dirnagl and Endres argue that despite the apparent translational failures in neuroprotection research, and counter to current nihilism, basic and preclinical stroke research has in fact been able to predict human pathophysiology, clinical phenotypes, and therapeutic outcomes. The understanding of stroke pathobiology that has been achieved through basic research has led to changes in stroke care whose value can be demonstrated. Preclinical investigations have informed the clinical realm even in the absence of intermediary phase 2 or phase 3 trials. Their arguments rest on examples of successful bench-to-bedside translation in which experimental studies preceded human trials and successfully predicted outcomes or phenotypes, as well as on examples of successful ‘back-translation’, where studies in animals recapitulated what we already knew to be true in human beings. An analysis of the reasons for the apparent (or only perceived) translational failures further strenghtens their proposition, and suggests measures to improve the positive predictive value of preclinical stroke research. Researchers, funding agencies, academic institutions, publishers, and professional societies should work together to harness the tremendous potential of basic and preclinical research, in stroke research as well as in other fields of medicine
Ulrich Dirnagl and Matthias Endres. Found in Translation: Preclinical Stroke Research Predicts Human Pathophysiology, Clinical Phenotypes, and Therapeutic Outcomes. Stroke. 2014; 45: 1510-1518