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

Fawcett, J. W., Curt, A., Steeves, J. D., Coleman, W. P., Tuszynski, M. H., Lammertse, D., Bartlett, P. F., Blight, A. R., Dietz, V., Ditunno, J., Dobkin, B. H., Havton, L. A., Ellaway, P. H., Fehlings, M. G., Privat, A., Grossman, R., Guest, J. D., Kleitman, N., Nakamura, M., Gaviria, M. and Short, D. (2007) 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. Spinal Cord, 45 3: 190-205. doi:10.1038/sj.sc.3102007


Author Fawcett, J. W.
Curt, A.
Steeves, J. D.
Coleman, W. P.
Tuszynski, M. H.
Lammertse, D.
Bartlett, P. F.
Blight, A. R.
Dietz, V.
Ditunno, J.
Dobkin, B. H.
Havton, L. A.
Ellaway, P. H.
Fehlings, M. G.
Privat, A.
Grossman, R.
Guest, J. D.
Kleitman, N.
Nakamura, M.
Gaviria, M.
Short, D.
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
Journal name Spinal Cord   Check publisher's open access policy
ISSN 1362-4393
Publication date 2007
Year available 2006
Sub-type Article (original research)
DOI 10.1038/sj.sc.3102007
Volume 45
Issue 3
Start page 190
End page 205
Total pages 16
Editor L. Illis
J. Wilde
Place of publication London
Publisher Nature Publishing Group
Collection year 2008
Language eng
Subject 320702 Central Nervous System
730104 Nervous system and disorders
C1
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 to 18 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.
Keyword Clinical Neurology
Randomized Controlled-trial
Neurologic Recovery
Tirilazad Mesylate
Motor Recovery
Methylprednisolone
Multicenter
Quadriplegia
Tetraplegia
Naloxone
ASIA
Q-Index Code C1
Q-Index Status Confirmed Code

 
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Created: Mon, 18 Feb 2008, 16:27:16 EST