title: The need to move from 6-minute walk distance to outcome trials in pulmonary arterial hypertension.
abstract: Assessment of change in exercise capacity using the 6-min walk distance (6MWD) test has been the primary end-point in the majority of pulmonary arterial hypertension (PAH) clinical trials. The 6MWD has some advantages as an end-point in such studies. It is simple and inexpensive to perform, reproducible and validated. In short-term studies with small patient numbers, as is typical in a rare disease like PAH, using change from baseline in 6MWD as the primary outcome measure demonstrated statistically significant differences between placebo and study drugs, leading to their approval. However, there have been increasing calls for clinical trials to employ primary end-points that reflect long-term disease progression and morbidity. While the 6MWD was initially considered to be a potentially reliable surrogate for disease progression in PAH, there is increasing evidence that this is not necessarily the case. Given this, there is a need to re-examine the role of 6MWD in PAH trials, and to evaluate the evidence supporting whether there is a need to move from 6MWD to more robust measures of clinical outcomes, such as morbidity and mortality. However, in the clinic the 6MWD test, alongside symptoms, haemodynamics and biomarkers, remains a useful tool in the assessment and management of PAH patients.
authors.affiliation: National Pulmonary Hypertension Unit, Mater Misericordiae University Hospital, Dublin, Ireland. 2 Service de Pneumologie, Hôpital Universitaire de Bicêtre, Université Paris-Sud, Le Kremlin Bicêtre, France.
authors.forename: Sean
authors.initials: S
authors.lastname: Gaine
authors.forename: Gérald
authors.initials: G
authors.lastname: Simonneau
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods*; D018450:Disease Progression; D023381:Endpoint Determination; D005080:Exercise Test; D017079:Exercise Tolerance; D065627:Familial Primary Pulmonary Hypertension; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis* / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D011237:Predictive Value of Tests; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome; D016138:Walking