The Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND): Test development and reliability

Abstract

The motor skills of patients with spinal muscular atrophy, type I (SMA-I) are very limited. It is difficult to quantify the motor abilities of these patients and as a result there is currently no validated measure of motor function that can be utilized as an outcome measure in clinical trials of SMA-I. We have developed the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (“CHOP INTEND”) to evaluate the motor skills of patients with SMA-I. The test was developed following the evaluation of 26 infants with SMA-I mean age 11.5 months (1.4–37.9 months) with the Test of Infant Motor Performance and The Children’s Hospital of Philadelphia Test of Strength in SMA, a newly devised motor assessment for SMA. Items for the CHOP INTEND were selected by an expert panel based on item mean and standard deviation, item frequency distribution, and Chronbach’s alpha. Intra-rater reliability of the resulting test was established by test–retest of 9 infants with SMA-I over a 2 month period; Intraclass correlation coefficient (ICC) (3,1) = 0.96. Interrater reliability was by video analysis of a mixed group of infants with neuromuscular disease by 4 evaluators; ICC (3,4) = 0.98 and in a group of 8 typically developing infants by 5 evaluators ICC (3,5) = 0.93. The face validity of the CHOP INTEND is supported by the use of an expert panel in item selection; however, further validation is needed. The CHOP INTEND is a reliable measure of motor skills in patients with SMA-I and neuromuscular disorders presenting in infancy.

Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy

“…5,6,12,15,16 Although the HINE-2 was not specifically developed to assess motor function in infants with spinal muscular atrophy, 13 it can be used to identify incremental changes in the achievement of motor milestones that are relevant among infants with spinal muscular atrophy type 1, 12 and the HINE-2 assessment can be performed reliably in a multicenter study.…”

“…Scores on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) range from 0 to 64, with higher scores indicating better motor function; a CHOP INTEND response was defined as an increase of at least 4 points from baseline in the CHOP INTEND score at the end-of-trial visit (day 183, 302, or 394). 15,16 A compound muscle action potential (CMAP) response was defined as an increase in the peroneal CMAP amplitude to at least 1 mV (or maintenance of an amplitude of ≥1 mV) at the end-of-trial visit (day 183, 302, or 394). Adverse events included all untoward events that occurred during the trial period, including those that were expected to occur in a population of infants with spinal muscular atrophy; details are provided in the Supplementary Appendix.…”

Baseline results of the NeuroNEXT spinal muscular atrophy infant biomarker study

“…After testing, all subjects were required to have a 20‐minute rest period that could include nursing/feeding. Subjects who scored less than 41 on the TIMSPI were then evaluated using The Children's Hospital of Philadelphia Infant Test for Neuromuscular Disorders (CHOP‐INTEND) which is a validated 16‐item, 64‐point scale shown to be reliable in SMA type 1 subjects 19, 24. Subjects scoring 41 or greater on the TIMPSI were evaluated using the Alberta Infant Motor Scale (AIMS), a 58‐item observational scale developed to assess motor development in children from birth until independent walking 25, 26…”

Observational study of spinal muscular atrophy type I and implications for clinical trials

“…15,16 The CHOP INTEND was performed on all subjects with SMA-I and, for comparison, 5 subjects with SMA-II. Motor function testing was performed by clinical evaluators after a training and reliability session and reliability was re-established annually.…”