Review

. 2018 Jul;56(7):628-642.

doi: 10.1038/s41393-018-0097-8. Epub 2018 Apr 27.

Lower extremity outcome measures: considerations for clinical trials in spinal cord injury

Marc Bolliger^{1

2}, Andrew R Blight³, Edelle C Field-Fote⁴, Kristin Musselman^{5

6}, Serge Rossignol⁷, Dorothy Barthélemy⁸, Laurent Bouyer⁹, Milos R Popovic^{10

11}, Jan M Schwab¹², Michael L Boninger¹³, Keith E Tansey¹⁴, Giorgio Scivoletto¹⁵, Naomi Kleitman¹⁶, Linda A T Jones¹⁶, Dany H Gagnon¹⁷, Sylvie Nadeau¹⁷, Dirk Haupt¹⁸, Lea Awai¹⁹, Chris S Easthope¹⁹, Björn Zörner¹⁹, Ruediger Rupp²⁰, Dan Lammertse²¹, Armin Curt^{19

22}, John Steeves¹⁸

Affiliations

¹ Spinal Cord Injury Center, University Hospital Balgrist, University Zurich, Zurich, Switzerland. marc.bolliger@balgrist.ch.
² Swiss Center for Clinical Movement Analysis (SCMA), Zurich, Switzerland. marc.bolliger@balgrist.ch.
³ Acorda Therapeutics, Ardsley, NY, USA.
⁴ Shepherd Center, Georgia Institute of Technology, School of Biological Sciences, Emory University School of Medicine, Division of Physical Therapy, Atlanta, GA, USA.
⁵ Toronto Rehabilitation Institute, University Health Network, Toronto, ON, Canada.
⁶ Department of Physical Therapy, University of Toronto, Toronto, ON, Canada.
⁷ Department of Neuroscience, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.
⁸ School of Rehabilitation, Faculty of Medicine, Université de Montréal, and Centre de recherche interdisciplinaire en réadaptation (CRIR), Institut universitaire sur la réadaptation en déficience physique de Montréal (IURDPM) du CIUSSS du Centre-Sud-de-l'Ile-de-Montréal, Montreal, QC, Canada.
⁹ Department of Rehabilitation, Faculty of Medicine, Université Laval, Québec, Canada.
¹⁰ Rehabilitation Engineering Laboratory, Toronto Rehabilitation Institute, University Health Network, Toronto, ON, Canada.
¹¹ Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada.
¹² Department of Neurology, Spinal Cord Injury Division and Departments of Neuroscience and Physical Medicine and Rehabilitation, The Neurological Institute, The Ohio State University, Wexner Medical Center, Columbus, OH, USA.
¹³ Department of Physical Medicine and Rehabilitation, University of Pittsburgh & Department of Veterans Affairs, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA.
¹⁴ Methodist Rehabilitation Center, University of Mississippi Medical Center and Jackson VA Medical Center, Jackson, MS, USA.
¹⁵ Spinal Cord Unit and Spinal Rehabilitation (SpiRe) laboratory, IRCCS Fondazione S. Lucia, Rome, Italy.
¹⁶ Craig H. Neilsen Foundation, Encino, CA, USA.
¹⁷ School of Rehabilitation, Université de Montréal and Pathokinesiology Laboratory, Centre for Interdisciplinary Research in Rehabilitation, Institut universitaire sur la réadaptation en déficience physique de Montréal, CIUSSS Centre-Sud-de-l'Île-de-Montréal, Montreal, QC, Canada.
¹⁸ University of British Columbia, Vancouver, BC, Canada.
¹⁹ Spinal Cord Injury Center, University Hospital Balgrist, University Zurich, Zurich, Switzerland.
²⁰ Spinal Cord Injury Center, Heidelberg University Hospital, Heidelberg, Germany.
²¹ Craig Hospital, Englewood, Colorado, University of Colorado School of Medicine, Colorado, USA.
²² Swiss Center for Clinical Movement Analysis (SCMA), Zurich, Switzerland.

PMID: 29700477
PMCID: PMC6131138
DOI: 10.1038/s41393-018-0097-8

Review

Lower extremity outcome measures: considerations for clinical trials in spinal cord injury

Marc Bolliger et al. Spinal Cord. 2018 Jul.

. 2018 Jul;56(7):628-642.

doi: 10.1038/s41393-018-0097-8. Epub 2018 Apr 27.

Authors

Affiliations

¹ Spinal Cord Injury Center, University Hospital Balgrist, University Zurich, Zurich, Switzerland. marc.bolliger@balgrist.ch.
² Swiss Center for Clinical Movement Analysis (SCMA), Zurich, Switzerland. marc.bolliger@balgrist.ch.
³ Acorda Therapeutics, Ardsley, NY, USA.
⁴ Shepherd Center, Georgia Institute of Technology, School of Biological Sciences, Emory University School of Medicine, Division of Physical Therapy, Atlanta, GA, USA.
⁵ Toronto Rehabilitation Institute, University Health Network, Toronto, ON, Canada.
⁶ Department of Physical Therapy, University of Toronto, Toronto, ON, Canada.
⁷ Department of Neuroscience, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.
⁸ School of Rehabilitation, Faculty of Medicine, Université de Montréal, and Centre de recherche interdisciplinaire en réadaptation (CRIR), Institut universitaire sur la réadaptation en déficience physique de Montréal (IURDPM) du CIUSSS du Centre-Sud-de-l'Ile-de-Montréal, Montreal, QC, Canada.
⁹ Department of Rehabilitation, Faculty of Medicine, Université Laval, Québec, Canada.
¹⁰ Rehabilitation Engineering Laboratory, Toronto Rehabilitation Institute, University Health Network, Toronto, ON, Canada.
¹¹ Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada.
¹² Department of Neurology, Spinal Cord Injury Division and Departments of Neuroscience and Physical Medicine and Rehabilitation, The Neurological Institute, The Ohio State University, Wexner Medical Center, Columbus, OH, USA.
¹³ Department of Physical Medicine and Rehabilitation, University of Pittsburgh & Department of Veterans Affairs, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA.
¹⁴ Methodist Rehabilitation Center, University of Mississippi Medical Center and Jackson VA Medical Center, Jackson, MS, USA.
¹⁵ Spinal Cord Unit and Spinal Rehabilitation (SpiRe) laboratory, IRCCS Fondazione S. Lucia, Rome, Italy.
¹⁶ Craig H. Neilsen Foundation, Encino, CA, USA.
¹⁷ School of Rehabilitation, Université de Montréal and Pathokinesiology Laboratory, Centre for Interdisciplinary Research in Rehabilitation, Institut universitaire sur la réadaptation en déficience physique de Montréal, CIUSSS Centre-Sud-de-l'Île-de-Montréal, Montreal, QC, Canada.
¹⁸ University of British Columbia, Vancouver, BC, Canada.
¹⁹ Spinal Cord Injury Center, University Hospital Balgrist, University Zurich, Zurich, Switzerland.
²⁰ Spinal Cord Injury Center, Heidelberg University Hospital, Heidelberg, Germany.
²¹ Craig Hospital, Englewood, Colorado, University of Colorado School of Medicine, Colorado, USA.
²² Swiss Center for Clinical Movement Analysis (SCMA), Zurich, Switzerland.

PMID: 29700477
PMCID: PMC6131138
DOI: 10.1038/s41393-018-0097-8

Abstract

Study design: This is a focused review article.

Objectives: To identify important concepts in lower extremity (LE) assessment with a focus on locomotor outcomes and provide guidance on how existing outcome measurement tools may be best used to assess experimental therapies in spinal cord injury (SCI). The emphasis lies on LE outcomes in individuals with complete and incomplete SCI in Phase II-III trials.

Methods: This review includes a summary of topics discussed during a workshop focusing on LE function in SCI, conceptual discussion of corresponding outcome measures and additional focused literature review.

Results: There are a number of sensitive, accurate, and responsive outcome tools measuring both quantitative and qualitative aspects of LE function. However, in trials with individuals with very acute injuries, a baseline assessment of the primary (or secondary) LE outcome measure is often not feasible.

Conclusion: There is no single outcome measure to assess all individuals with SCI that can be used to monitor changes in LE function regardless of severity and level of injury. Surrogate markers have to be used to assess LE function in individuals with severe SCI. However, it is generally agreed that a direct measurement of the performance for an appropriate functional activity supersedes any surrogate marker. LE assessments have to be refined so they can be used across all time points after SCI, regardless of the level or severity of spinal injury.

Sponsors: Craig H. Neilsen Foundation, Spinal Cord Outcomes Partnership Endeavor.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

**Fig. 1**
Range of walking deficit over which each “well-reviewed” LE-outcome measure can be applied. There is currently no validated outcome measure that can cover the whole spectrum of SCI from the most severely to mildly affected patients. 3D-Gait analysis consists of kinematics, kinetics and electromyography

See this image and copyright information in PMC

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Lower extremity outcome measures: considerations for clinical trials in spinal cord injury

Affiliations

Lower extremity outcome measures: considerations for clinical trials in spinal cord injury

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Affiliations

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Conflict of interest statement

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