Can Animal Models of Disease Reliably Inform Human Studies?

Animal experiments have contributed much to our understanding of mechanisms of disease, but their value in predicting the effectiveness of treatment strategies in clinical trials has remained controversial [1-3].In fact, clinical trials are essential because animal studies do not predict with sufficient certainty what will happen in humans.In a review of animal studies published in seven leading scientific journals of high impact, about one-third of the studies translated at the level of human randomised trials, and one-tenth of the interventions, were subsequently approved for use in patients [1].However, these were studies of high impact (median citation count, 889), and less frequently cited animal research probably has a lower likelihood of translation to the clinic.Depending on one's perspective, this attrition rate of 90% may be viewed as either a failure or as a success, but it serves to illustrate the magnitude of the difficulties in translation that beset even findings of high impact.Recent examples of therapies that failed in large randomised clinical trials despite substantial reported benefit in a range of animal studies include enteral probiotics for the prevention of infectious complications of acute pancreatitis, NXY-059 for acute ischemic stroke, and a range of strategies to reduce lethal reperfusion injury in patients with acute myocardial infarction [4][5][6][7].In animal models of acute ischemic stroke, about 500 ''neuroprotective'' treatment strategies have been reported to improve outcome, but only aspirin and very early intravenous thrombolysis with alteplase (recombinant tissueplasminogen activator) have proved effec-tive in patients, despite numerous clinical trials of other treatment strategies [8,9].Research in Translation discusses health interventions in the context of translation from basic to clinical research, or from clinical evidence to practice.