@article{20035e9758f04b9b84bd15dd9ada6d32,
title = "Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: Spontaneous recovery after spinal cord injury and statistical power needed for therapeutic clinical trials",
abstract = "The International Campaign for Cures of Spinal Cord Injury Paralysis (ICCP) supported an international panel tasked with reviewing the methodology for clinical trials in spinal cord injury (SCI), and making recommendations on the conduct of future trials. This is the first of four papers. Here, we examine the spontaneous rate of recovery after SCI and resulting consequences for achieving statistically significant results in clinical trials. We have reanalysed data from the Sygen trial to provide some of this information. Almost all people living with SCI show some recovery of motor function below the initial spinal injury level. While the spontaneous recovery of motor function in patients with motor-complete SCI is fairly limited and predictable, recovery in incomplete SCI patients (American spinal injury Association impairment scale (AIS) C and AIS D) is both more substantial and highly variable. With motor complete lesions (AIS A/AIS B) the majority of functional return is within the zone of partial preservation, and may be sufficient to reclassify the injury level to a lower spinal level. The vast majority of recovery occurs in the first 3 months, but a small amount can persist for up to18 months or longer. Some sensory recovery occurs after SCI, on roughly the same time course as motor recovery. Based on previous data of the magnitude of spontaneous recovery after SCI, as measured by changes in ASIA motor scores, power calculations suggest that the number of subjects required to achieve a significant result from a trial declines considerably as the start of the study is delayed after SCI. Trials of treatments that are most efficacious when given soon after injury will therefore, require larger patient numbers than trials of treatments that are effective at later time points. As AIS B patients show greater spontaneous recovery than AIS A patients, the number of AIS A patients requiring to be enrolled into a trial is lower. This factor will have to be balanced against the possibility that some treatments will be more effective in incomplete patients. Trials involving motor incomplete SCI patients, or trials where an accurate assessment of AIS grade cannot be made before the start of the trial, will require large subject numbers and/or better objective assessment methods.",
keywords = "ASIA, Clinical assessment, Clinical examination, Clinical trial, Motor system, Power calculation, Sensory system, Spinal cord injury",
author = "Fawcett, {J. W.} and A. Curt and Steeves, {J. D.} and Coleman, {W. P.} and Tuszynski, {M. H.} and D. Lammertse and Bartlett, {P. F.} and Blight, {A. R.} and V. Dietz and J. Ditunno and Dobkin, {B. H.} and Havton, {L. A.} and Ellaway, {P. H.} and Fehlings, {M. G.} and A. Privat and R. Grossman and Guest, {J. D.} and N. Kleitman and M. Nakamura and M. Gaviria and D. Short",
note = "Funding Information: The ICCP is an affiliation of {\textquoteleft}not for profit{\textquoteright} organizations, which aims to facilitate the translation of valid treatments for SCI paralysis. The panel{\textquoteright}s travel and accommodation expenses have been supported by the following ICCP member organizations: Christopher Reeve Foundation (USA), Institut pour la Recherche sur la Mo{\"e}lle Epini{\`e}re (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, with ICORD (International Collaboration On Repair Discoveries) in Vancouver providing all logistical coordination. The membership of the panel is shown on the list of authors for this and the three accompanying papers, with all panel members volunteering their time and effort. Funding Information: 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{\textquoteright} travel and accommodation expenses. The ICCP represents the following member organizations: Christopher Reeve Foundation (USA), Institut pour la Recherche sur la Mo{\"e}lle Epini{\`e}re (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.",
year = "2007",
month = mar,
day = "30",
doi = "10.1038/sj.sc.3102007",
language = "English",
volume = "45",
pages = "190--205",
journal = "Spinal Cord",
issn = "1362-4393",
publisher = "Springer Nature",
number = "3",
}