1. ¹Department of Neurosciences, Center for Neural Repair, University of California,-San Diego, La Jolla, CA, USA
2. ²Department of Neurology, Veterans Administration Medical Center, La Jolla, CA, USA
3. ³ICORD, University of British Columbia and Vancouver Coastal Health Research Institute, Vancouver, British Columbia, Canada
4. ⁴Cambridge University Centre for Brain Repair, Robinson Way, Cambridge, UK
5. ⁵Craig Hospital, Englewood, CO, USA
6. ⁶Department of Physical Medicine and Rehabilitation, University of Colorado at Denver and Health Sciences Center, Denver, CO, USA
7. ⁷Research Ethics Program and Department of Pathology, University of California - San Diego, La Jolla, CA, USA
8. ⁸Institute for OneWorld Health, San Francisco, CA, USA
9. ⁹Department of Rehabilitation Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA, USA
10. ¹⁰Department of Surgery, University of Toronto, Division of Neurosurgery, Toronto, Ontario, Canada
11. ¹¹Department of Neurosurgery, University of Miami, Miami, FL, USA
12. ¹²Department of Movement & Balance, Division of Neuroscience & Mental Health, Imperial College London, London, UK
13. ¹³National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
14. ¹⁴National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA
15. ¹⁵Acorda Therapeutics, Inc., Hawthorne, New York, NY, USA
16. ¹⁶Spinal Cord Injury Center, Balgrist University Hospital, Zurich, Switzerland
17. ¹⁷Department of Neurology, University of California Los Angeles, Geffen School of Medicine, Neurologic Rehabilitation and Research Program, Los Angeles, CA, USA
18. ¹⁸Methodist Neurological Institute, Houston, TX, USA
19. ¹⁹Institut des Neurosciences - CHU St Eloi, INSERM U-583, Montpellier Cedex, France

Correspondence: MH Tuszynski, Department of Neurosciences, Center for Neural Repair, University of California- San Diego, La Jolla, CA 92093, USA

Abstract

The International Campaign for Cures of Spinal Cord Injury Paralysis established a panel tasked with reviewing the methodology for clinical trials for spinal cord injury (SCI), and making recommendations on the conduct of future trials. This is the third of four papers. It examines inclusion and exclusion criteria that can influence the design and analysis of clinical trials in SCI, together with confounding variables and ethical considerations. Inclusion and exclusion criteria for clinical trials should consider several factors. Among these are (1) the enrollment of subjects at appropriate stages after SCI, where there is supporting data from animal models or previous human studies; (2) the severity, level, type, or size of the cord injury, which can influence spontaneous recovery rate and likelihood that an experimental treatment will clinically benefit the subject; and (3) the confounding effects of various independent variables such as pre-existing or concomitant medical conditions, other medications, surgical interventions, and rehabilitation regimens. An issue of substantial importance in the design of clinical trials for SCI is the inclusion of blinded assessments and sham surgery controls: every effort should be made to address these major issues prospectively and carefully, if clear and objective information is to be gained from a clinical trial. The highest ethical standards must be respected in the performance of clinical trials, including the adequacy and clarity of informed consent.