Bench to bedside: the quest for quality in experimental stroke research.
Over the past decades, great progress has been made in clinical as well as experimental stroke research. Disappointingly, however, hundreds of clinical trials testing neuroprotective agents have failed despite efficacy in experimental models. Recently, several systematic reviews have exposed a number of important deficits in the quality of preclinical stroke research. Many of the issues raised in these reviews are not specific to experimental stroke research, but apply to studies of animal models of disease in general. It is the aim of this article to review some quality-related sources of bias with a particular focus on experimental stroke research. Weaknesses discussed include, among others, low statistical power and hence reproducibility, defects in statistical analysis, lack of blinding and randomization, lack of quality-control mechanisms, deficiencies in reporting, and negative publication bias. Although quantitative evidence for quality problems at present is restricted to preclinical stroke research, to spur discussion and in the hope that they will be exposed to meta-analysis in the near future, I have also included some quality-related sources of bias, which have not been systematically studied. Importantly, these may be also relevant to mechanism-driven basic stroke research. I propose that by a number of rather simple measures reproducibility of experimental results, as well as the step from bench to bedside in stroke research may be made more successful. However, the ultimate proof for this has to await successful phase III stroke trials, which were built on basic research conforming to the criteria as put forward in this article.
Dirnagl
Ulrich
U
Department of Experimental Neurology, Center for Stroke Research, Humboldt-Universität Berlin, Universitätsklinikum Charite, Berlin, Germany. ulrich.dirnagl@charite.de
D000818:Animals; D035843:Biomedical Research / Q000639:trends; D006801:Humans; D017594:Publication Bias; D011786:Quality Control; D016032:Randomized Controlled Trials as Topic; D012107:Research Design / Q000639:trends; D020521:Stroke