Of Mice And Men

I have run into zealous naysayers from both camps. From a clinical researcher: “Human trials are the ultimate, difficult to run, very different from animal studies which may have no clinical relevance.” From a bench scientist: “Epidemiologic studies are trash in, trash out. Well designed animal studies are real science that will advance health.”
There’s an element of truth to both sides. Patient trials are complex and costly, liable to inter-subject variation (diabetic nephropathy is notorious), lag-time bias, selection bias, and in the case of non-blinded trials there is potential treatment effect due to patient preference (see blog by #AHAEarlyCareerBlogger @LeonieKlompstra). Thus truly successful RCTs are uncommon. At #ISC18, it was remarkable to hear the findings from the DEFUSE 3 trial which showed that in select patients with suitable brain imaging profile, thrombectomy for ischemic stroke beyond the traditional 6-hour window (a 6-16 hour timeframe was specified) conferred improved functional and mortality outcomes compared to medical therapy alone. The trial was terminated early due to efficacy superiority, with a staggering number needed to treat (NNT) of two. The NNT declaration incited spontaneous cheering from the audience – uncommon at scientific meetings where we politely applaud at the end of talks – because it is rare to see such robust positive RCT outcomes.
For identifying at-risk cohorts or new targets for preventative healthcare, epidemiology is essential. The inherent limitation here is that correlation is not causality. With a large database (thousands of patients) sophisticated tools for multivariate and time-varying adjustments can result in a dizzying array of associations that have to be carefully interpreted. (Simple illustrative case: positive correlation between higher number of firemen in areas with more fires. The firemen didn’t cause the fires. I hope.)
Animal studies have their niche in that they allow for evaluation of disease or drug pathways in a living model when a human study is not feasible. Animal studies are fraught with their own set of flaws, the most prominent being translational failure due to the model not adequately replicating human disease. Dr. Jun Chen gave the Thomas Willis Lecture at #ISC18 and pointed out the importance of streamlining integrative methods in stroke models to make them clinically relevant. The majority of animal trials will not translate into approved clinical interventions, but still serve to advance our understanding of pathophysiology and drug effects. Some major discoveries (including insulin, erythropoietin, klotho, aspirin, and numerous anti-cancer therapies) would not have been possible without judicious animal research.
Advancements in patient care would not be possible without both basic science and patient trials (some impressive folks out there wear both hats!). Bench and clinical research each have their strengths and limitations and deserve to be critically interpreted, while prioritizing exchange of ideas and constructive feedback to collectively move medicine forward.
Wei Ling Lau Headshot
Wei Ling Lau, MD is Assistant Professor in Nephrology at University of California-Irvine, where she studies vascular calcification and brain microbleeds in chronic kidney disease. She is currently funded by an AHA Innovative Research Grant, and has been a speaker for CardioRenal University and the American Society of Nephrology.