Prognostic factors for changes in the timed 4-stair climb in patients with Duchenne muscular dystrophy, and implications for measuring drug efficacy: A multi-institutional collaboration
| العنوان: | Prognostic factors for changes in the timed 4-stair climb in patients with Duchenne muscular dystrophy, and implications for measuring drug efficacy: A multi-institutional collaboration |
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| المؤلفون: | Nathalie Goemans, Brenda Wong, Marleen Van den Hauwe, James Signorovitch, Gautam Sajeev, David Cox, John Landry, Madeline Jenkins, Ibrahima Dieye, Zhiwen Yao, Intekhab Hossain, Susan J Ward, Collaborative Trajectory Analysis Project (cTAP) |
| المصدر: | PLoS ONE, Vol 15, Iss 6, p e0232870 (2020) PLoS ONE |
| بيانات النشر: | PUBLIC LIBRARY SCIENCE, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Heredity, Physiology, Genetic Linkage, Duchenne muscular dystrophy, Walking, Duchenne Muscular Dystrophy, 030105 genetics & heredity, Pediatrics, Muscular Dystrophies, DISEASE, law.invention, Tadalafil, Efficacy, 0302 clinical medicine, Randomized controlled trial, DESIGN, law, Medicine and Health Sciences, Medicine, Child, Multidisciplinary, Organic Compounds, Prognosis, Phase III clinical investigation, Multidisciplinary Sciences, Chemistry, Neurology, Neuromuscular Agents, X-Linked Traits, Sex Linkage, Ambulatory, Physical Sciences, Disease Progression, Science & Technology - Other Topics, Steroids, TRIAL, Research Article, medicine.medical_specialty, Drug Research and Development, Adolescent, Science, ATALUREN, Placebo, Research and Analysis Methods, 03 medical and health sciences, DRISAPERSEN, Diagnostic Medicine, Genetics, Humans, Clinical Trials, Computer Simulation, Clinical Genetics, Pharmacology, Science & Technology, business.industry, Biological Locomotion, Clinical study design, Organic Chemistry, Chemical Compounds, Biology and Life Sciences, medicine.disease, Clinical trial, Muscular Dystrophy, Duchenne, Sample size determination, Sample Size, Physical therapy, Exercise Test, Clinical Medicine, business, 030217 neurology & neurosurgery, Follow-Up Studies |
| الوصف: | The timed 4-stair climb (4SC) assessment has been used to measure function in Duchenne muscular dystrophy (DMD) practice and research. We sought to identify prognostic factors for changes in 4SC, assess their consistency across data sources, and the extent to which prognostic scores could be useful in DMD clinical trial design and analysis. Data from patients with DMD in the placebo arm of a phase 3 trial (Tadalafil DMD trial) and two real-world sources (Universitaire Ziekenhuizen, Leuven, Belgium [Leuven] and Cincinnati Children's Hospital Medical Center [CCHMC]) were analyzed. One-year changes in 4SC completion time and velocity (stairs/second) were analyzed. Prognostic models included age, height, weight, steroid use, and multiple timed function tests and were developed using multivariable regression, separately in each data source. Simulations were used to quantify impacts on trial sample size requirements. Data on 1-year changes in 4SC were available from the Tadalafil DMD trial (n = 92) Leuven (n = 67), and CCHMC (n = 212). Models incorporating multiple timed function tests, height, and weight significantly improved prognostic accuracy for 1-year change in 4SC (R2: 29%-36% for 4SC velocity, and 29%-34% for 4SC time) compared to models including only age, baseline 4SC and steroid duration (R2:8%-17% for 4SC velocity and 2%-13% for 4SC time). Measures of walking and rising ability contributed important prognostic information for changes in 4SC. In a randomized trial with equal allocation to treatment and placebo, adjustment for such a prognostic score would enable detection (at 80% power) of a treatment effect of 0.25 stairs/second with 100-120 patients, compared to 170-190 patients without prognostic score adjustment. Combining measures of ambulatory function doubled prognostic accuracy for 1-year changes in 4SC completion time and velocity. Randomized clinical trials incorporating a validated prognostic score could reduce sample size requirements by approximately 40%. Knowledge of important prognostic factors can also inform adjusted comparisons to external controls. ispartof: PLOS ONE vol:15 issue:6 ispartof: location:United States status: published |
| وصف الملف: | Electronic-eCollection |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c05aa276ab26d60ebede754c9790ea90Test https://lirias.kuleuven.be/handle/20.500.12942/704020Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c05aa276ab26d60ebede754c9790ea90 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |