Suitability of external controls for drug evaluation in Duchenne muscular dystrophy

Nathalie Goemans, James Signorovitch, Gautam Sajeev, Zhiwen Yao, Heather Gordish-Dressman, Craig M. Mcdonald, Krista Vandenborne, Debra Miller, Susan J. Ward, Eugenio Mercuri, Eugenio Maria Mercuri

Risultato della ricerca: Contributo in rivistaArticolo in rivista

2 Citazioni (Scopus)


Objective: To evaluate the suitability of real-world data (RWD) and natural history data (NHD) for use as external controls in drug evaluations for ambulatory Duchenne muscular dystrophy (DMD). Methods: The consistency of changes in the 6-minute walk distance (Δ6MWD) was assessed across multiple clinical trial placebo arms and sources of NHD/RWD. Six placebo arms reporting 48-week Δ6MWD were identified via literature review and represented 4 sets of inclusion/exclusion criteria (n = 383 patients in total). Five sources of RWD/NHD were contributed by Universitaire Ziekenhuizen Leuven, DMD Italian Group, The Cooperative International Neuromuscular Research Group, ImagingDMD, and the PRO-DMD-01 study (n = 430 patients, in total). Mean Δ6MWD was compared between each placebo arm and RWD/NHD source after subjecting the latter to the inclusion/exclusion criteria of the trial for baseline age, ambulatory function, and steroid use. Baseline covariate adjustment was investigated in a subset of patients with available data. Results: Analyses included ∼1,200 patient-years of follow-up. Differences in mean Δ6MWD between trial placebo arms and RWD/NHD cohorts ranged from -19.4 m (i.e., better outcomes in RWD/NHD) to 19.5 m (i.e., worse outcomes in RWD/NHD) and were not statistically significant before or after covariate adjustment. Conclusions: We found that Δ6MWD was consistent between placebo arms and RWD/NHD subjected to equivalent inclusion/exclusion criteria. No evidence for systematic bias was detected. These findings are encouraging for the use of RWD/NHD to augment, or possibly replace, placebo controls in DMD trials. Multi-institution collaboration through the Collaborative Trajectory Analysis Project rendered this study feasible.
Lingua originaleEnglish
pagine (da-a)e1381-e1391
Stato di pubblicazionePubblicato - 2020


  • duchenne


Entra nei temi di ricerca di 'Suitability of external controls for drug evaluation in Duchenne muscular dystrophy'. Insieme formano una fingerprint unica.

Cita questo