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Neurorehabil Neural Repair. 2015 Oct;29(9):867-77. doi: 10.1177/1545968315570322. Epub 2015 Feb 2.

Toward Inclusive Trial Protocols in Heterogeneous Neurological Disorders: Prediction-Based Stratification of Participants With Incomplete Cervical Spinal Cord Injury.

Author information

1
Spinal Cord Injury Center, Balgrist University Hospital, Zurich, Switzerland Department of Biostatistics, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland ltanadini@paralab.balgrist.ch.
2
Department of Biostatistics, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.
3
Craig H. Neilsen Foundation, Encino, CA, USA.
4
Craig Hospital, Englewood, CO, USA Department of Physical Medicine and Rehabilitation, University of Colorado Denver, Aurora, CO, USA.
5
Trauma Center Bayreuth, Bayreuth, Germany EMSCI Study Group.
6
EMSCI Study Group Trauma Center Murnau, Murnau, Germany.
7
EMSCI Study Group Spinal Cord Injury Center, Heidelberg University Hospital, Heidelberg, Germany.
8
Spinal Cord Injury Center, Balgrist University Hospital, Zurich, Switzerland EMSCI Study Group.
9
ICORD, University of British Columbia and Vancouver Coastal Health, Vancouver, Canada.

Abstract

BACKGROUND:

Several novel drug- and cell-based potential therapies for spinal cord injury (SCI) have either been applied or will be considered for future clinical trials. Limitations on the number of eligible patients require trials be undertaken in a highly efficient and effective manner. However, this is particularly challenging when people living with incomplete SCI (iSCI) represent a very heterogeneous population in terms of recovery patterns and can improve spontaneously over the first year after injury.

OBJECTIVE:

The current study addresses 2 requirements for designing SCI trials: first, enrollment of as many eligible participants as possible; second, refined stratification of participants into homogeneous cohorts from a heterogeneous iSCI population.

METHODS:

This is a retrospective, longitudinal analysis of prospectively collected SCI data from the European Multicenter study about Spinal Cord Injury (EMSCI). We applied conditional inference trees to provide a prediction-based stratification algorithm that could be used to generate decision rules for the appropriate inclusion of iSCI participants to a trial.

RESULTS:

Based on baseline clinical assessments and a defined subsequent clinical endpoint, conditional inference trees partitioned iSCI participants into more homogeneous groups with regard to the illustrative endpoint, upper extremity motor score. Assuming a continuous endpoint, the conditional inference tree was validated both internally as well as externally, providing stable and generalizable results.

CONCLUSION:

The application of conditional inference trees is feasible for iSCI participants and provides easily implementable, prediction-based decision rules for inclusion and stratification. This algorithm could be utilized to model various trial endpoints and outcome thresholds.

KEYWORDS:

clinical trial design; inclusion exclusion criteria; unbiased recursive partitioning; upper extremity motor score

PMID:
25644238
DOI:
10.1177/1545968315570322
[Indexed for MEDLINE]

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