P.2.8 The 6-min walk test and clinical endpoints in Duchenne MD: Reliability, validity, and clinically-important differences
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- 作者：C.M. McDonald ; E.K. Henricson ; R.T. Abresch ; J.M. Florence ; M. Eagle ; E. Gappmaier ; A. Glanzman ; R. Spiegel ; J. Barth ; G. Elfring ; A. Reha ; S.W. Peltz ; P.T.C. Study Group
- 刊名：Neuromuscular Disorders
- 出版年：2013
- 出版时间：October, 2013
- 年：2013
- 卷：23
- 期：9-10
- 页码：751
- 全文大小：47 K
文摘
Introduction: An international clinical trial enrolled 174 ambulatory males ?5 years old with nonsense mutation Duchenne muscular dystrophy (DMD). Pre-treatment data provide insight into reliability, concurrent validity, and minimal clinically important differences (MCID) of the 6-min walk test (6MWT), and other endpoints. Methods: Eligibility criteria included nonsense-mediated severe dystrophinopathy, males ?5 years, and ambulatory (defined as ability to walk >75 m on the 6MWT). A total of 174 patients, 70 % of whom were treated with corticosteroids, were randomized into three treatment groups for the PTC124-GD-007 Ataluren clinical trial and evaluated initially at screening and baseline visits. The 6 min walk distance (6MWD) was defined as primary endpoint and other secondary and exploratory endpoints included timed function tests ¡§C TFTs (time to stand from supine, time to climb 4 stairs, time to run/walk 10 m, and methods during TFTs), quantitative strength by hand-held myometry (knee extensors, knee flexors, elbow extensors, and elbow flexors), the PedsQL physical functioning scale, and energy expenditure index determined by heart rate measurement during the 6-min walk test. Results: The 6MWT proved feasible and reliable in a multicenter context. Concurrent validity with other endpoints was excellent. The MCID for 6MWD was 28.5 and 31.7 m based on two statistical distribution methods. Discussion: The ratio of MCID to baseline mean is lower for 6MWD than for other endpoints demonstrating the sensitivity of this endpoint. The 6MWD showed an MCID of approximately 30 m - similar to the magnitude of change observed in previous registration trials focused on other clinical populations. The 6MWD is a reliable, valid and clinically meaningful primary endpoint and an optimal primary endpoint for DMD clinical trials that are therapeutically focused on preservation of ambulatory functioning and slowing disease progression.