Reliability and Validity of the 6‐Minute Walk Test in Hypophosphatasia

Abstract

This investigation evaluated the reliability and validity of the 6‐Minute Walk Test (6MWT) in patients with pediatric hypophosphatasia (HPP). Children (aged 6 to 12 years; n = 11), adolescents (13 to 17 years; n = 4), and adults (18 to 65 years; n = 9) completed the 6MWT at screening and baseline in two clinical studies of asfotase alfa. Test‐retest reliability of the 6MWT, evaluated with Pearson's correlation coefficients ( r ) for screening versus baseline, was high for children ( r = 0.95; p < 0.0001), adolescents ( r = 0.81; p = 0.125), and adults ( r = 0.94; p = 0.0001). The most conservative minimal clinically important differences, estimated using distribution‐based methods, were 31 m (children and adults) and 43 m (adolescents). In children, the 6MWT correlated significantly with scores on measures of skeletal disease, which included the Radiographic Global Impression of Change scale ( r = 0.50; p < 0.0001) and the Rickets Severity Scale ( r = −0.78; p < 0.0001), such that distance walked increased as the severity of skeletal disease decreased. Significant ( p < 0.0001) correlations with the 6MWT distance walked were also observed for children with scores on parent‐reported measures of disability ( r = −0.67), ability to function in activities of daily living ( r = 0.71 to 0.77), and parent‐reported measures of pain ( r = −0.39). In adolescents and adults, 6MWT distance walked correlated significantly ( p < 0.05) with measures of lower extremity function ( r = 0.83 and 0.60, respectively), total pain severity ( r = −0.41 and −0.36, respectively), and total pain interference ( r = −0.41 and −0.49, respectively). Collectively, these data indicate that the 6MWT is a reliable, valid measure of physical functioning in patients with pediatric HPP. © 2018 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

Physical Function and Health‐Related Quality of Life in Adults Treated With Asfotase Alfa for Pediatric‐Onset Hypophosphatasia

“…(25) Of the primary outcome measures of physical function (6MWT, TUG test, SPPB, and grip strength), both the 6MWT and the TUG test, as well as two of the three components of the SPPB, showed statistically significant improvements from baseline to sometime during 12 months of treatment, which indicates the effectiveness of asfotase alfa in improving the functional health of adult patients with pediatric-onset HPP. Minimum clinically important differences for adults with HPP have been established for the 6MWT (31 m) (26) ; in this study, the median 6MWT distance increased by a clinically meaningful 39 m at 6 months and 53 m at 12 months of treatment compared with baseline. Although improvements observed by 6 months were not significant, statistically significant improvements were noted at 12 months.…”

Marked motor function improvement in a 32-year-old woman with childhood-onset hypophosphatasia by asfotase alfa therapy: Evaluation based on standardized testing batteries used in Duchenne muscular dystrophy clinical trials

“…The 6MWT was used as a validated measure in combination with multiple exploratory tests, including the Bruininks-Oseretsky Test of Motor Proficiency (Running Speed and Agility subset and Strength subtest) for evaluating gross motor function, hand-held dynamometry for testing muscle strength of the hip extensors and abductors, the Lower Extremity Functional Scale to calculate the performance of transitional movements, locomotion, climbing stairs, and squatting, and the Brief Pain Inventory-Short Form for assessing pain [ 12 ]. Phillips et al also showed high test-retest reliability (r = 0.95; p < 0.0001) for the 6MWT in HPP as well as sufficient validity (i.e., walking distance increased as the severity of skeletal disease decreased) [ 13 ].…”

“…Indicating the smallest benefit of value to the patient [ 14 ], the minimally clinically important difference (MCID) of the 6MWT is reportedly 31 m in adults with pediatric-onset HPP and 43 m in adolescents with pediatric-onset HPP [ 13 ]. In the present case, the 6MWT distance surpassed both MCID values: 48 m at 3 months of treatment and 102 m at 12 months.…”

Testes funcionais validados em indivíduos hospitalizados e não hospitalizados: revisão sistemática

“…Dos 42 artigos, 27 eram estudos observacionais longitudinais 6,7,[9][10][11]13,[15][16][17][18][19][20]22,24,27,[29][30][31][35][36][37][38]40,41,43,45,46 , nove observacionais de corte transversal 14,21,23,25,26,39,42,44,47 e seis utilizaram dados de ensaios clínicos 8,12,28,[32][33][34] . Apenas três foram realizados com indivíduos hospitalizados, sendo um em sujeitos com lesão traumática cerebral 30 , outro em indivíduos durante ou fora do tratamento do câncer 40 e outro em sujeitos com doença renal terminal .…”

“…Em relação à execução dos testes, foram realizados em corredores de 70 m 30,34 , 50 m 6 , 40 m 14,22,47 , 30 m 11,17,24,26,31,38,40,42,47 , 25 m 13,19,39 , 20 m 15,21,28,33,43,44 , 15 m 26,35 , 10 m 41 , 8 m 20 , um campo 40 m × 20 m 46 , em pista retangular 10 m x 50 m 41 , de 12 m x 6 m 30 , em corredor circular de 125 m 25 e em percurso oval de 150 e 250 pés 17 . Dezenove estudos seguiram as diretrizes da American Thoracic Society (ATS) 8,9,11,13,14,17,18,22,23,27,29,31,35,36,39,40,42,46,47 .…”