The 6-Minute Walk Test and Person-Reported Outcomes in Boys with Duchenne Muscular Dystrophy and Typically Developing Controls: Longitudinal Comparisons and Clinically-Meaningful Changes Over One Year

Abstract

Introduction: Data is currently lacking anchoring a 30-meter longitudinal change in walking ability by 6-minute walk test (6MWT) in Duchenne muscular dystrophy as a minimal clinically important difference and “clinically meaningful” person-reported outcomes (PROs) at differing levels of ambulatory ability. Methods: We describe correlation between measures, 1-year change in measures, and correlation of 1-year changes between measures for the six-minute walk test (6MWT), 10-meter run/walk velocity, PedsQL and POSNA Pediatric Outcomes Data Collection Instrument (PODCI) in 24 4-12 year old. ambulatory DMD and 36 typical controls, and determine if minimal clinically important differences (MCID) of PROs contribute to different estimates of 6-minute walk distance (6MWD) change at differing levels of ability. Results: PedsQL total and physical function and PODCI global, transfer/mobility and sports/physical function PROs demonstrated significant differences between DMD and controls (p<0.00001). In DMD, 6MWD and 10-meter run/walk velocity were correlated with PODCI domain scores, with the transfer/mobility scale showing the strongest relationship (r=0.79 and r=0.76). In DMD, 6MWD distance and 10-meter run/walk velocity weakly correlated with PedsQL domain scores. In DMD, 6MWD, 10-meter run/walk velocity, and PODCI global and transfer and basic mobility demonstrated significant one-year change and exceeded the amount of change representing MCID. In DMD, 6MWD change highly correlated with change in PODCI global and PODCI transfer/mobility scores (r=0.76 and r=0.93). PODCI global and PODCI transfer/mobility scales provided the best estimates of 6MWT performance. A “meaningful” 4.5 point change in a low PODCI transfer / basic mobility score of 30 to 34.5 was associated with a 5.6m 6MWD change from 150.3 to 155.9m. At PODCI levels closer to normative levels for healthy controls, the change in 6MWD distance associated with a “meaningful” change in PODCI scores was almost 46m. Discussion: At lower levels of function, smaller increases in 6MWD result in meaningful change in quality of life (QoL) instrument scores. At higher levels of function, larger increases may be necessary to achieve the same QoL change score.

Measuring functional recovery in stroke patients: the responsiveness of ACTIVLIM-Stroke

“…As such, they capture more details than the MRS, permitting more discrimination and consequently more sensitivity to small changes. In addition, the 6MWT, which was designed to reflect functional recovery in chronic disabled people,9 10 is a specific test of walking capacity. It measures only part of physical performance (ie, locomotion) and does not evaluate other subdomains of functional status and, therefore, may not be sensitive to small changes occurring in a subdomain other than locomotion.…”

“…The 6MWT is a performance test that evaluates walking endurance; it consists in recording the distance (m) a subject walked in 6 min 8. This test is demonstrated to reflect people functional status 9 10. Participants performed the 6MWT by walking as quickly as possible on a flat ground square path with a 50–85 m perimeter marked on the floor.…”

Translational and Regulatory Challenges for Exon Skipping Therapies

“…For DMD recently results of natural history studies have been published (Goemans et al, 2013;Henricson et al, 2013a;Henricson et al, 2013b;Mazzone et al, 2013;McDonald et al, 2013a;McDonald et al, 2013b;Pane et al, 2014). This information should be useful to set inclusion criteria and select the group most likely to show clinical benefit over placebo.…”

“…What clinical benefit entails will obviously vary for different diseases, depending on their symptoms and rate of disease progression. For DMD a 30 meter difference in the 6 minute walking distance between placebo-treated and drug-treated patients was proposed as clinically relevant benefit (Henricson et al, 2013a), and used in the recent Translarna CHMP positive opinion.…”

Valores de referencia del test de marcha en 6 minutos para niños y adolescentes sanos colombianos de 7 a 17 años de edad

“…Se han publicado diferentes estudios: en adultos sanos, para establecer valores de referencia normales, como los realizados por Enright P. en 1998 6 ; en niños sanos, diferentes estudios entre los cuales se tienen los realizados en China 7 , Brasil 8 , Chile 5 , Suiza 9 y Austria, 10 relacionando índice de masa corporal y test de marcha en 6 minutos( 11 ; en pacientes con peso normal y sobrepeso 12 ; en niños y adolescentes con fibrosis quística 13 ; también se han realizado estudios implementando esta prueba en pacientes con bronquiolitis obliterante 14 , en patología congénita cardiaca 15 , en asma 16 , diabetes mellitus 17 , obesidad 18 y enfermedad renal crónica 19 , en enfermedades neuromusculares como la enfermedad de Pompe( 20 ) y distrofia muscular de Duchenne. 21 A pesar de los múltiples estudios existentes a nivel mundial, esta prueba clínica continúa siendo de poca aplicación en población pediátrica, posiblemente debido a la falta de información y difusión respecto a los beneficios y facilidad de aplicación tanto en niños sanos como con algún tipo de enfermedad; con el objeto de valorar la tolerancia al ejercicio fí-sico y de manera indirecta poder valorar el consumo de oxígeno, es decir, la capacidad aeróbica, así mismo se ha presentado dificultad para obtener valores de referencia en esta población.…”