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Design and selection of endpoints used in clinical trials is a complex and compelling topic; the diverse needs of clinicians, patients and regulatory authorities represent a challenge in devising the most relevant, meaningful yet practical measures. In trials of therapies for pulmonary arterial hypertension (PAH), a variety of endpoints have been used, including assessments of exercise capacity (6-min walk distance [6MWD]), functional class, hemodynamics, and time to clinical worsening. Most have relied upon 6MWD as the primary endpoint.Accumulating experience and expertise suggests that the relevance of the 6-min walk test as a stand-alone measure of efficacy is now a topic for consideration. Furthermore, 6MWD tends to correlate poorly with other endpoints and, most importantly, there is no linear relationship between 6MWD and morbidity/mortality. Although no linear relationship has been identified with other endpoints, time to clinical worsening may be considered a better endpoint for assessing the effectiveness of PAH therapies, in particular the impact of treatment on disease progression, because it is very relevant to the clinical outcome of patients. Treatment of mildly symptomatic patients, for example, has demonstrated a clear delay in time to clinical worsening and the endpoint might be better suited than others to demonstrate the efficacy of combination therapy.As the field of PAH develops and progresses, time to clinical worsening may be the best way currently of distinguishing between the increasing number of treatment options available. A clear definition must, therefore, be established, with adjudication by an expert panel; the needs of clinicians, patients, and regulators should be balanced when selecting the most appropriate endpoints.