Editorial Replication and reproducibility in spinal cord injury research Oswald Steward a, b, c, d, ⁎, Phillip G. Popovich e, f , W. Dalton Dietrich g, h , Naomi Kleitman i a Reeve-Irvine Research Center, University of California at Irvine School of Medicine, Irvine, CA 92697-4265, USA b Department of Anatomy & Neurobiology, University of California at Irvine School of Medicine, Irvine, CA 92697-4265, USA c Department of Neurobiology & Behavior, University of California at Irvine School of Medicine, Irvine, CA 92697-4265, USA d Department of Neurosurgery, University of California at Irvine School of Medicine, Irvine, CA 92697-4265, USA e Center for Brain and Spinal Cord Repair, The Ohio State University College of Medicine, Columbus, Ohio 432, USA f Department of Neuroscience, The Ohio State University College of Medicine, Columbus, Ohio 43210, USA g The Miami Project to Cure Paralysis, University of Miami, Leonard M. Miller School of Medicine, Miami, FL 33136-1060, USA h Department of Neurological Surgery, University of Miami, Leonard M. Miller School of Medicine, Miami, FL 33136-1060, USA i National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-9525, USA abstract article info Article history: Received 23 June 2011 Accepted 28 June 2011 Available online 10 November 2011 Keywords: Replication Regeneration This special issue of Experimental Neurology compiles a series of papers that either explicitly replicate published studies or retest phenomena reported in previous publications. The explicit replications were carried out as part of the “Facilities of Research Excellence—Spinal Cord Injury” (FORE—SCI) program launched by the National Institute of Neurological Disorders and Stroke (NINDS) in 2003. Here, we review the FORE—SCI replication experiments published prior to those in this special issue. We then discuss emerging issues regarding replication and reproducibility in spinal cord injury research, especially in terms of potential translation to clinical trials. © 2011 Elsevier Inc. All rights reserved. Introduction In 2003, the National Institute of Neurological Disorders and Stroke (NINDS) launched a new program called “Facilities of Research Excellence—Spinal Cord Injury” (FORE—SCI). This program provided funding via contracts to carry out independent replication of published studies that report experimental interventions that reduce secondary injury, improve recovery, or enhance axon regeneration after SCI. Two FORE—SCI replication contracts were awarded in 2003, one to the University of California, Irvine under direction of O. Steward at the Reeve- Irvine Research Center (UCI/RIRC), and the other to the University of Miami, under direction of W. D. Dietrich at The Miami Project to Cure Paralysis (UM/TMP). The program was renewed in 2008 through a competitive solicitation, with contracts awarded again to UCI and a new contract site, The Ohio State University (OSU), under direction of P. Popovich. This special issue of Experimental Neurology compiles several papers resulting from the FORE—SCI program that explicitly replicate published studies, as well as other papers that retest phenomena reported in previous publications. Here, we discuss the organization and impact of the FORE-SCI replication program, review previously published FORE—SCI replication studies and discuss general issues regarding replication, reproducibility and potential translatability in SCI research. The FORE—SCI replication program The FORE—SCI replication program was established by NINDS after extensive discussions among the spinal cord injury (SCI) research community of two perceived problems. First, every year for at least the preceding two decades, numerous papers appeared reporting that some intervention, drug or biologic (e.g. cell transplant), reduces injury severity or functional impairment (i.e., is neuroprotective), improves recovery of function, or enhances regenerative growth following SCI. Despite this apparent progress at the basic science level, not one of the many strategies reported as having promising effects were translated into successful therapies. Indeed, only recently was one of these interventions carried forward through preclinical development to testing in a clinical trial. Second, many reports of striking effects were never followed up either by the original authors or by others, or if they were, the results were not reported in the scientific literature. What happened? Were the results not reproducible? If there were failures to replicate, these were rarely communicated to the community at large, although rumors abound (“I tried that and it didn't work”). It is impossible to interpret or judge the validity of the rumors or whether the rumored replications were thorough and had been carried out properly. One possibility is that the lack of follow-up indicates a lack of robustness of the findings. This may have been detected by the Experimental Neurology 233 (2012) 597–605 ⁎ Corresponding author at: Reeve-Irvine Research Center, University of California, Irvine, 1105 Gillespie Neuroscience Research Facility, Irvine, CA 92697-4265, USA. Fax: + 1 949 824 2625. E-mail address: osteward@uci.edu (O. Steward). 0014-4886/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.expneurol.2011.06.017 Contents lists available at ScienceDirect Experimental Neurology journal homepage: www.elsevier.com/locate/yexnr