The minimal important difference in the 6-minute walk test for patients with pulmonary arterial hypertension.
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ABSTRACT: Rationale
Although commonly used as the primary outcome measure of clinical trials in pulmonary arterial hypertension (PAH), the minimal important difference (MID) of the 6-minute walk test (6MWT) has not been well defined for this population of patients.Objectives
To estimate the MID in the 6MWT in patients with PAH.Methods
Study subjects from the clinical trial of tadalafil in PAH, a 16-week, parallel-group, randomized clinical trial of patients who were treatment naive or on background therapy with an endothelin receptor antagonist, were eligible. 6MWT was performed using a standardized protocol. Distributional and anchor-based methods were used to estimate the MID; the latter method used the Physical Component Summary Score (PCS) of the Medical Outcomes Study 36-item short form (SF-36).Measurements and main results
Four hundred five subjects were analyzed. Domains of the SF-36 were weakly to modestly associated with 6MWT. Change in the PCS of the SF-36 was most strongly associated with change in 6MWT (r = 0.40, P < 0.001) and thus was selected as the anchor for subsequent anchor-based analyses. Distributional analyses yielded estimates of the MID ranging from 25.1 to 38.5 m, whereas anchor-based analyses yielded an estimate of 38.6 m.Conclusions
Using both distributional and anchor-based methods, the estimated consensus MID in the 6MWT for PAH is approximately 33 m. These results have important implications for (1) assessing treatment responses from clinical trials and metaanalyses of specific PAH therapy, and (2) sample size calculations for future study design.
SUBMITTER: Mathai SC
PROVIDER: S-EPMC3443803 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Several patient-reported outcome measures have been developed to assess health status in pulmonary arterial hypertension. The required change in instrument scores needed, to be seen as meaningful to the individual, however remain unknown. We sought to identify minimal clinically important differences in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) and to validate these against objective markers of functional capacity. Minimal clinically important differences were established from a discovery cohort (n = 129) of consecutive incident cases of idiopathic pulmonary arterial hypertension with CAMPHOR scores recorded at treatment-naïve baseline and 4-12 months following pulmonary arterial hypertension therapy. An independent validation cohort (n = 87) was used to verify minimal clinically important differences. Concurrent measures of functional capacity relative to CAMPHOR scores were collected. Minimal clinically important differences were derived using anchor- and distributional-based approaches. In the discovery cohort, mean (SD) was 54.4 (16.4) years and 64% were female. Most patients (63%) were treated with sequential pulmonary arterial hypertension therapy. Baseline CAMPHOR scores were: Symptoms, 12 (7); Activity, 12 (7) and quality of life, 10 (7). Pulmonary arterial hypertension treatment resulted in significant improvements in CAMPHOR scores (p < 0.05). CAMPHOR minimal clinically important differences averaged across methods for health status improvement were: Symptoms, -4 points; Activity, -4 points and quality of life -3 points. CAMPHOR Activity score change ≥minimal clinically important difference was associated with significantly greater improvement in six-minute walk distance, in both discovery and validation populations. In conclusion, CAMPHOR scores are responsive to pulmonary arterial hypertension treatment. Minimal clinically important differences in pulmonary hypertension-specific scales may provide useful insights into treatment response in future clinical trials.
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Project description:ObjectiveThe 6-min walk distance (6MWD), a widely used test of functional capacity, has limited evidence of construct validity among patients surviving acute respiratory failure (ARF) and ARDS. The objective of this study was to examine construct validity and responsiveness and estimate minimal important difference (MID) for the 6MWD in patients surviving ARF/ARDS.MethodsFor this secondary data analysis of four international studies of adult patients surviving ARF/ARDS (N = 641), convergent and discriminant validity, known group validity, predictive validity, and responsiveness were assessed. MID was examined using anchor- and distribution-based approaches. Analyses were performed within studies and at various time points after hospital discharge to examine generalizability of findings.ResultsThe 6MWD demonstrated good convergent and discriminant validity, with moderate to strong correlations with physical health measures (|r| = 0.36-0.76) and weaker correlations with mental health measures (|r| = 0.03-0.45). Known-groups validity was demonstrated by differences in 6MWD between groups with differing muscle strength and pulmonary function (all P < .01). Patients reporting improved function walked farther, supporting responsiveness. 6MWD also predicted multiple outcomes, including future mortality, hospitalization, and health-related quality of life. The 6MWD MID, a small but consistent patient-perceivable effect, was 20 to 30 m. Findings were similar for 6MWD % predicted, with an MID of 3% to 5%.ConclusionsIn patients surviving ARF/ARDS, the 6MWD is a valid and responsive measure of functional capacity. The MID will facilitate planning and interpretation of future group comparison studies in this population.
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Project description:BackgroundPulmonary arterial hypertension (PAH) is a chronic disease of the pulmonary vasculature that can lead to heart failure and premature death. Assessment of patients with PAH includes performing a 6-minute walk test (6MWT) in clinics. We developed a smartphone app to compute the walked distance (6MWD) indoors, by counting U-turns, and outdoors, by using satellite positioning.ObjectiveThe goal of the research was to assess (1) accuracy of the indoor 6MWTs in clinical settings, (2) validity and test-retest reliability of outdoor 6MWTs in the community, (3) compliance, usability, and acceptance of the app, and (4) feasibility of pulse oximetry during 6MWTs.MethodsWe tested the app on 30 PAH patients over 6 months. Patients were asked to perform 3 conventional 6MWTs in clinic while using the app in the indoor mode and one or more app-based 6MWTs in outdoor mode in the community per month.ResultsBland-Altman analysis of 70 pairs of conventional versus app-based indoor 6MWDs suggests that the app is sometimes inaccurate (14.6 m mean difference, lower and upper limit of agreement: -133.35 m to 162.55 m). The comparison of 69 pairs of conventional 6MWDs and community-based outdoor 6MWDs within 7 days shows that community tests are strongly related to those performed in clinic (correlation 0.89), but the interpretation of the distance should consider that differences above the clinically significant threshold are not uncommon. Analysis of 89 pairs of outdoor tests performed by the same patient within 7 days shows that community-based tests are repeatable (intraclass correlation 0.91, standard error of measurement 36.97 m, mean coefficient of variation 12.45%). Questionnaires and semistructured interviews indicate that the app is usable and well accepted, but motivation to use it could be affected if the data are not used for clinical decision, which may explain low compliance in 52% of our cohort. Analysis of pulse oximetry data indicates that conventional pulse oximeters are unreliable if used during a walk.ConclusionsApp-based outdoor 6MWTs in community settings are valid, repeatable, and well accepted by patients. More studies would be needed to assess the benefits of using the app in clinical practice.Trial registrationClinicalTrials.gov NCT04633538; https://clinicaltrials.gov/ct2/show/NCT04633538.
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Project description:OBJECTIVE:To determine Glittre-ADL test minimal important difference in patients with chronic obstructive pulmonary disease. METHODS:This is quasi-experimental study. Sixty patients with moderate to very severe chronic obstructive pulmonary disease (age 64.1, SD=9.09 years; forced expiratory volume in the first second 37.9, SD=13.0% predicted participated in a pulmonary rehabilitation program based on physical training, conducted over 24 sessions supervised, three times a week, including aerobic training in treadmill and resistance training for upper limbs and lower limbs. The main outcomes were the Glittre-ADL test and six-minute walk test, before and after 24 sessions of pulmonary rehabilitation. The minimal important difference was established using the distribution and anchor-based methods. RESULTS:Patients improved their functional capacity after the pulmonary rehabilitation. The effect sizes of Glittre-ADL test and six-minute walk test improvement were similar (0.45 vs 0.44, respectively). The established minimal important differences ranged from -0.38 to -1.05. The reduction of 0.38min (23s) corresponded to a sensitivity of 64% and a specificity of 69% with an area under the curve of 0.66 (95%CI 0.51-0.81; p=0.04). Subjects who achieved the minimal important difference of -0.38min for the Glittre-ADL test had a superior improvement of approximately 42m in the six-minute walk test when compared to patients who did not. CONCLUSIONS:The present findings suggest -0.38min as the minimal important difference in the time spent in the Glittre-ADL test after 24 sessions of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease. TRIAL REGISTRATION:NCT03251781 (https://clinicaltrials.gov/ct2/show/NCT03251781).
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Project description:Functional tests such as Motor Function Measure-32 (MFM-32), supine to stand, ascend/descend stairs permit the assessment of task-specific motor function in neuromuscular disease (NMD). The 6-min walk test (6MWT), though functional, is primarily used to assess endurance and disease progression in children with neuromuscular disorders. Barriers to 6MWT administration, in this population, can include reduced attention span due to age and inability to tolerate test length due to weakness. We propose task-specific functional deficits are related to endurance. Additionally, the 2-min walk test (2MWT) could effectively replace the 6MWT in this population. Seventy-seven participants, ages 5-18, with a variety of neuromuscular disorders performed the 6MWT, timed functional tests (TFT), and the MFM-32. Correlation and paired t-test analyses were used to compare the distance walked in the first 2 min (2MWD) to the distance walked in the entire 6 min (6MWD) and to the functional outcome measures above. The 2MWD strongly correlated with 6MWD and the other outcome measures. Paired t-test analysis also showed that the 2MWD did not differ from the distance walked in the last 2 min of the 6MWT. Although equivalence testing could not reject the claim that this difference exceeded the upper practical limit of 9.5 m, it only showed a modest overestimation of the 4-6MWD compared with the 2MWD. Together, our results support the ability of the 2MWD to predict the 6MWD, specifically in the pediatric neuromuscular disease population.
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Project description:The six-minute walk test (6MWT) is a simple test that is widely used to assess functional exercise capacity in patients with idiopathic pulmonary fibrosis (IPF). Patients with IPF have reduced exercise capacity due to a number of factors, such as impaired respiratory mechanics and circulatory problems. As a self-paced and usually submaximal exercise test, the 6MWT reflects the exercise level of everyday activities. Variables measured during the 6MWT, such as six-minute walk distance (6MWD) and desaturation, are strong predictors of mortality in patients with IPF. However, the results of a 6MWT are affected by numerous factors, including age, body size, comorbidities and the use of supplemental oxygen during the test, and these need to be borne in mind when interpreting the results of individual and serial tests. Clinical studies, including trials of potential therapies for IPF, have differed in the methodology used to implement the 6MWT, hindering the comparison of results across studies. In this review, I describe the utility of the 6MWT in patients with IPF and provide recommendations for standardisation of the test for use both in clinical practice and research. A brief video on how to set up and administer the 6MWT is available at http://www.usscicomms.com/respiratory/lancaster/6mwt/.
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Project description:Morquio A syndrome is an ultra-rare, inherited lysosomal storage disorder associated with progressive, multi-systemic clinical impairments, causing gradual loss of functional capacity and endurance, impaired quality of life, and early mortality. Studies in Morquio A patients have used the 6-min walk test (6MWT) to assess functionality and endurance and to evaluate disease progression or efficacy of treatment. The objective of the present study was to review minimal clinically important differences (MCIDs) for the 6MWT reported for disease states that widely use the 6MWT to evaluate clinical benefit and to discuss the results in view of the challenges in estimating MCID for ultra-rare diseases, using the case of elosulfase alfa in Morquio A patients. A systematic literature search was performed using Embase and Medline to identify studies specifically estimating the MCID using either anchor-based or distribution-based methods. A total of 19 publications on 17 studies were identified; none of these included patients with Morquio A syndrome or the wider disease category of lysosomal storage disorders. Therefore, the MCIDs determined by studies in patients with respiratory, cardiovascular, or musculoskeletal disease were compared to changes in the 6MWT seen in Morquio A patients in the pivotal phase 3 clinical trial of elosulfase alfa enzyme replacement therapy. The literature review showed a mean MCID for the 6MWT of 7% change (range 3-15%) in studies using anchor-based methods and a 9% change (range 4-16%) using distribution-based methods. Results of the elosulfase alfa clinical trial and its extension showed a placebo-adjusted 14.9% improvement in the 6MWT from baseline at week 24, which was greater than the mean MCID based on the results of the systematic literature review. After 2 years, 6MWT distance increased by a mean of 20.7% from baseline in a modified per-protocol population, versus a reduction of 6.9% in comparable untreated patients from the MorCAP natural history study over the same period. Although further research is required to establish the MCID of the 6MWT in Morquio A patients, the presented data provide further evidence for the positive effect of elosulfase alfa in this patient population.
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