The minimal important difference in the 6-minute walk test for patients with pulmonary arterial hypertension.
BACKGROUND
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.


OBJECTIVE
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).


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.
Johns Hopkins University School of Medicine, Division of Pulmonary and Critical Care Medicine, 1830 E. Monument Street, Room 516, Baltimore, MD 21205, USA. smathai4@jhmi.edu
Stephen C
SC
Mathai
Milo A
MA
Puhan
Diana
D
Lam
Robert A
RA
Wise
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D002243:Carbolines / Q000627:therapeutic use; D003627:Data Interpretation, Statistical; D005080:Exercise Test / Q000706:statistics & numerical data*; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods*; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use; D015203:Reproducibility of Results; D000068581:Tadalafil; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D002243:Carbolines; D058986:Phosphodiesterase 5 Inhibitors; D000068581:Tadalafil