1. ¹ICORD, University of British Columbia (UBC) and Vancouver Coastal Health (VCH) Research Institute, Vancouver, BC, Canada
2. ²Craig Hospital, Englewood, CO, USA
3. ³Cambridge University Centre for Brain Repair, Robinson Way, Cambridge, UK
4. ⁴Center for Neural Repair, University of California at San Diego, La Jolla, CA, USA
5. ⁵Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA
6. ⁶Department of Movement and Balance, Division of Neuroscience and Mental Health, Imperial College London, Charing Cross Campus, London, UK
7. ⁷University of Toronto, Krembil Neuroscience Center, Head Spine and Spinal Cord Injury Program, Toronto Western Hospital, Toronto, Ontario, Canada
8. ⁸Department of Neurological Surgery and the Miami Project to Cure Paralysis, Lois Pope LIFE Center, Miami, FL, USA
9. ⁹National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA
10. ¹⁰Queensland Brain Institute, University of Queensland, St Lucia, Queensland, Australia
11. ¹¹Acorda Therapeutics, Hawthorne, NY, USA
12. ¹²Spinal Cord Injury Center, Balgrist University Hospital, Zurich, Switzerland
13. ¹³Department of Neurology, University of California Los Angeles, Geffen School of Medicine, Neurologic Rehabilitation and Research Program, Los Angeles, CA, USA
14. ¹⁴Baylor College of Medicine, Department of Neurosurgery, One Baylor Plaza, Houston, TX, USA
15. ¹⁵Midlands Centre for Spinal Injuries, Robert Jones and Agnes Hunt Orthopaedic and District Hospital NHS Trust, Oswestry, Shropshire, UK
16. ¹⁶Department of Orthopaedic Surgery, Keio University, School of Medicine, Tokyo, Japan
17. ¹⁷WPCMath, Buffalo, NY, USA
18. ¹⁸Institut des Neurosciences – CHU St Eloi, INSERM U-583, Montpellier, France

Correspondence: J Steeves, ICORD, University of British Columbia (UBC) and Vancouver Coastal Health (VCH) Research Institute, c/o 2469-6270 University Boulevard, Vancouver, BC, Canada V6T 1Z4

Abstract

An international panel reviewed the methodology for clinical trials of spinal cord injury (SCI), and provided recommendations for the valid conduct of future trials. This is the second of four papers. It examines clinical trial end points that have been used previously, reviews alternative outcome tools and identifies unmet needs for demonstrating the efficacy of an experimental intervention after SCI. The panel focused on outcome measures that are relevant to clinical trials of experimental cell-based and pharmaceutical drug treatments. Outcome measures are of three main classes: (1) those that provide an anatomical or neurological assessment for the connectivity of the spinal cord, (2) those that categorize a subject's functional ability to engage in activities of daily living, and (3) those that measure an individual's quality of life (QoL). The American Spinal Injury Association impairment scale forms the standard basis for measuring neurologic outcomes. Various electrophysiological measures and imaging tools are in development, which may provide more precise information on functional changes following treatment and/or the therapeutic action of experimental agents. When compared to appropriate controls, an improved functional outcome, in response to an experimental treatment, is the necessary goal of a clinical trial program. Several new functional outcome tools are being developed for measuring an individual's ability to engage in activities of daily living. Such clinical end points will need to be incorporated into Phase 2 and Phase 3 trials. QoL measures often do not correlate tightly with the above outcome tools, but may need to form part of Phase 3 trial measures.