A newly developed analytical procedure was applied to evaluate longitudinal treatment effects in Duchenne muscular dystrophy (DMD) using the North Star Ambulatory Assessment (NSAA) data, researchers recently reported in Muscle & Nerve.

“The unique approach presented here answers a different clinical question by investigating the longitudinal profile of the treatment effect over time, rather than evaluating the effect at a single, fixed time point only,” the study authors explained.

By applying the LWYY approach (named after Lin, Wei, Yang, and Ying), McDonald et al found that the curve for the group-wise mean cumulative number of failures was steeper for placebo than ataluren after 16 weeks, as well as for prednisone/prednisolone compared to deflazacort after 8 weeks. Thereafter, the curves in each comparison pair continued to diverge.

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Cumulative NSAA item failure rates were reduced by 27% for ataluren vs placebo (rate ratio, 0.73, 95% CI, 0.55-0.97, P =.027) and 28% for deflazacort vs prednisone/prednisolone (rate ratio, 0.72, 95% CI, 0.53-0.96, P =.028). A previous single time point analysis showed that patients in the ataluren group experienced a 31% reduced risk of loss of function compared to the placebo group.

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This type of analysis, the authors said, is particularly important when assessing progressive diseases such as DMD, as it allows to evaluate the totality of evidence from multiple outcome data over time, thereby complementing the traditional fixed time point analyses.

To test the procedure, the study authors used NSAA data from the phase 3 study on ataluren. They collected cumulative counts of failures to perform each item at specific time points over 48 weeks for each patient.

They then constructed treatment group-wise mean cumulative item failure count curves to compare ataluren vs placebo groups and deflazacort vs prednisone/prednisolone groups among placebo-treated patients. The sharper the curve, the worse the outcome.

The NSAA is a functional 17 item-based scale designed to evaluate ambulatory performance in patients with DMD.


McDonald CM, Wei LJ, Flanigan KM, et al. Evaluating longitudinal therapy effects via the North Star Ambulatory Assessment. Muscle Nerve. Published online August 12, 2021. doi:10.1002/mus.27396

Phase 3 study of ataluren in participants with nonsense mutation Duchenne muscular dystrophy (nmDMD) (ACT DMD). ClinicalTrials.gov. April 8, 2013. Updated August 4, 2020. Accessed August 18, 2021.