Novel approaches to analysis of the North Star Ambulatory Assessment (NSAA) in Duchenne muscular dystrophy (DMD): Observations from a phase 2 trial

PLoS One. 2022 Aug 23;17(8):e0272858. doi: 10.1371/journal.pone.0272858. eCollection 2022.

Abstract

Introduction: The North Star Ambulatory Assessment (NSAA) tool is a key instrument for measuring clinical outcomes in patients with Duchenne muscular dystrophy (DMD). To gain a better understanding of the longitudinal utility of the NSAA, we evaluated NSAA data from a phase II trial of 120 patients with DMD treated with domagrozumab or placebo.

Methods: The NSAA exploratory analyses included assessment of individual skills gained/lost, total skills gained/lost, cumulative loss of function, and the impact of transient loss of function due to a temporary disability on NSAA total score (temporary zero score).

Results: There was no significant difference in the total number of NSAA skills gained (mean 1.41 and 1.04, respectively; p = 0.3314) or lost (3.90 vs. 5.0; p = 0.0998) between domagrozumab- vs. placebo-treated patients at week 49. However, domagrozumab-treated patients were less likely to lose the ability to perform a NSAA item (hazard ratio 0.80, 95% confidence interval [CI]: 0.65-0.98, p = 0.029) over 48-weeks vs. placebo-treated patients. When temporary zero scores were changed to "not obtainable" (8 values from 7 patients), domagrozumab-treated patients scored higher on the NSAA total score versus placebo-treated patients (difference at week 49: 2.0, 95% CI: 0.1-3.9, p = 0.0359).

Conclusions: These exploratory analyses reveal additional approaches to interpreting the NSAA data beyond just change in NSAA total score. These observations also highlight the importance of reporting items as "not obtainable" for a patient with a temporary/transient physical disability that impacts their ability to perform the NSAA test.

Clinicaltrials.gov identifier: NCT02310763.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Muscular Dystrophy, Duchenne*
  • Outcome Assessment, Health Care
  • Physical Therapy Modalities

Associated data

  • ClinicalTrials.gov/NCT02310763

Grants and funding

This study was sponsored by Pfizer. The funder was involved in design and management of study B5161002; ClinicalTrials.gov: NCT02310763) from which data in the current manuscript are derived, and in data collection and analysis. The funder also provided support in the form of salaries for authors Jeffrey P. Palmer, Shannon Marraffino, and Lawrence Charnas. The specific roles of these authors are articulated in the ‘author contributions’ section. Medical writing support was provided by Vardit Dror, PhD, and Karen Burrows, MPhil, of Engage Scientific Solutions (Horsham, UK), which was funded by Pfizer.