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.
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Acknowledgements
We are grateful for the support of The International Campaign for Cures of spinal cord injury Paralysis (ICCP), which provided the funding for the authors' travel and accommodation expenses. The ICCP represents the following member organizations: Christopher Reeve Foundation (USA), Institut pour la Recherche sur la Moëlle Epinière (FRA), International Spinal Research Trust (UK), Japan Spinal Cord Foundation, Miami Project to Cure Paralysis (USA), Paralyzed Veterans of America (USA), Rick Hansen Man In Motion Foundation (CAN), SpinalCure Australia, and Spinal Research Fund of Australia. We thank the European Multicenter study in Spinal Cord Injury (EM-SCI) for sharing their data on spontaneous recovery after spinal cord injury. ICORD (International Collaboration on Repair Discoveries) in Vancouver provided all logistical coordination and support. All panel members (authors) volunteered their time and effort. Finally, we are most grateful for the input and constructive comments from a countless number of SCI investigators over the past 2.5 years.
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Steeves, J., Lammertse, D., Curt, A. et al. Guidelines for the conduct of clinical trials for spinal cord injury (SCI) as developed by the ICCP panel: clinical trial outcome measures. Spinal Cord 45, 206–221 (2007). https://doi.org/10.1038/sj.sc.3102008
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