McDonald, CM;
Wei, L-J;
Flanigan, KM;
Elfring, G;
Trifillis, P;
Muntoni, F;
(2021)
Evaluating longitudinal therapy effects via the North Star Ambulatory Assessment.
Muscle & Nerve
10.1002/mus.27396.
(In press).
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Abstract
Introduction/Aims: In comparative studies, treatment effects are typically evaluated at a specific time point. When data are collected periodically, an alternative, clinically meaningful approach could be used to assess the totality of treatment effects. We applied a well-developed analytical procedure for evaluating longitudinal treatment effects using North Star Ambulatory Assessment (NSAA) data for illustration. / Methods: The NSAA comprises 17 scorable items/outcomes that measure changes in motor function. Using NSAA data from the published ataluren phase 3, randomized, placebo-controlled trial (NCT01826487), cumulative counts of failures to perform each item (transition from 2/1 [able/impaired] to 0 [unable]) were collected at specified time points for each patient over 48 wk. Treatment group-wise mean cumulative item failure count curves were constructed, comparing ataluren versus placebo and deflazacort versus prednisone/prednisolone among placebo-treated patients. The steeper the curve, the worse the outcome. A clinically meaningful summary of the between-group difference was provided for each comparison. / Results: The curve was uniformly steeper for placebo than ataluren after 16 wk and for prednisone/prednisolone than deflazacort after 8 wk. The two curves in each comparison continued to diverge thereafter, indicating sustained treatment benefits over time. Using a unique analytical approach, cumulative failure rates were reduced, on average, by 27% for ataluren versus placebo (rate ratio, 0.73; 95% confidence interval [CI], 0.55–0.97; p = .027) and 28% for deflazacort versus prednisone/prednisolone (rate ratio, 0.72; 95% CI, 0.53–0.96; p = .028). / Discussion: Unlike fixed-time analyses, this analytical approach enabled demonstration of cumulative, longitudinal treatment effects over time using repeatedly measured NSAA observations.
| Type: | Article |
|---|---|
| Title: | Evaluating longitudinal therapy effects via the North Star Ambulatory Assessment |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/mus.27396 |
| Publisher version: | https://doi.org/10.1002/mus.27396 |
| Language: | English |
| Additional information: | Copyright © 2021 The Authors. Muscle & Nerve published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
| Keywords: | Duchenne muscular dystrophy, efficacy, motor function, outcome measure, treatment |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Neurosciences Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10134963 |
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