Biomaterial Database

Developing a Natural History Progression Model for Duchenne Muscular Dystrophy Using the Six-Minute Walk Test. 2017

Lora Hamuro, and Phyllis Chan, and Giridhar Tirucherai, and Malaz AbuTarif

Department of Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, Princeton, New Jersey, USA.

The 6-minute walk test (6MWT) is used as a clinical endpoint to evaluate drug efficacy in Duchenne Muscular Dystrophy (DMD) trials. A model was developed using digitized 6MWT data that estimated two slopes and two intercepts to characterize 6MWT improvement during development and 6MWT decline. Mean baseline 6MWT was 362 (±87) meters. The model predicted an improvement at a rate of 20 meters/year (95% confidence interval (CI) = 9.4-30) up until 10 years old (95% CI = 6.78-13.1), and then a decline at a rate of 85 meters/year (95% CI = 72-98). Interpatient slope variability for improvement and decline were similar at 21.9 percentage of coefficient of variation (%CV) and 23.3%CV, respectively. Model simulations using age demographics from a previous DMD natural history study could reasonably predict the trend in improvement and decline in the 6MWT. This model can be used to quantitate individual patient trajectories, identify prognostic factors for disease progression, and evaluate drug effect.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D002648	Child	A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL.	Children
D002675	Child, Preschool	A child between the ages of 2 and 5.	Children, Preschool,Preschool Child,Preschool Children
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000070857	Walk Test	A measure of endurance tests that show how far and fast an individual can walk without stopping within a certain period of time.	6-Min Walk Test,Six-Minute Walk Test,6-Minute Walk Test,Endurance Shuttle Walk Test,Incremental Shuttle Walk Test,6 Min Walk Test,6 Minute Walk Test,6-Min Walk Tests,6-Minute Walk Tests,Six Minute Walk Test,Six-Minute Walk Tests,Test, 6-Min Walk,Test, 6-Minute Walk,Test, Six-Minute Walk,Test, Walk,Tests, 6-Min Walk,Tests, 6-Minute Walk,Tests, Six-Minute Walk,Tests, Walk,Walk Test, 6-Min,Walk Test, 6-Minute,Walk Test, Six-Minute,Walk Tests,Walk Tests, 6-Min,Walk Tests, 6-Minute,Walk Tests, Six-Minute
D000293	Adolescent	A person 13 to 18 years of age.	Adolescence,Youth,Adolescents,Adolescents, Female,Adolescents, Male,Teenagers,Teens,Adolescent, Female,Adolescent, Male,Female Adolescent,Female Adolescents,Male Adolescent,Male Adolescents,Teen,Teenager,Youths
D018450	Disease Progression	The worsening and general progression of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.	Clinical Course,Clinical Progression,Disease Exacerbation,Exacerbation, Disease,Progression, Clinical,Progression, Disease
D020388	Muscular Dystrophy, Duchenne	An X-linked recessive muscle disease caused by an inability to synthesize DYSTROPHIN, which is involved with maintaining the integrity of the sarcolemma. Muscle fibers undergo a process that features degeneration and regeneration. Clinical manifestations include proximal weakness in the first few years of life, pseudohypertrophy, cardiomyopathy (see MYOCARDIAL DISEASES), and an increased incidence of impaired mentation. Becker muscular dystrophy is a closely related condition featuring a later onset of disease (usually adolescence) and a slowly progressive course. (Adams et al., Principles of Neurology, 6th ed, p1415)	Becker Muscular Dystrophy,Duchenne Muscular Dystrophy,Muscular Dystrophy, Becker,Muscular Dystrophy, Pseudohypertrophic,Becker's Muscular Dystrophy,Cardiomyopathy, Dilated, 3B,Cardiomyopathy, Dilated, X-Linked,Childhood Muscular Dystrophy, Pseudohypertrophic,Childhood Pseudohypertrophic Muscular Dystrophy,Duchenne and Becker Muscular Dystrophy,Duchenne-Becker Muscular Dystrophy,Duchenne-Type Progressive Muscular Dystrophy,Muscular Dystrophy Pseudohypertrophic Progressive, Becker Type,Muscular Dystrophy, Becker Type,Muscular Dystrophy, Childhood, Pseudohypertrophic,Muscular Dystrophy, Duchenne Type,Muscular Dystrophy, Duchenne and Becker Types,Muscular Dystrophy, Pseudohypertrophic Progressive, Becker Type,Muscular Dystrophy, Pseudohypertrophic Progressive, Duchenne Type,Muscular Dystrophy, Pseudohypertrophic, Childhood,Progressive Muscular Dystrophy, Duchenne Type,Pseudohypertrophic Childhood Muscular Dystrophy,Pseudohypertrophic Muscular Dystrophy, Childhood,Duchenne Becker Muscular Dystrophy,Duchenne Type Progressive Muscular Dystrophy,Muscular Dystrophy, Becker's,Muscular Dystrophy, Duchenne-Becker,Pseudohypertrophic Muscular Dystrophy