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Traditional endpoints in trials of therapies for pulmonary arterial hypertension (PAH), including 6-min walk distance, are associated with significant limitations. Time to clinical worsening (TTCW) may represent an alternative, and although it is being considered as a primary endpoint in future trials, it will ultimately require refinement before it can be broadly applied.Discussions with regulators about TTCW are ongoing, and there are several potential strategies that could be applied to enhance its robustness. For example, reliability and reproducibility could be increased if each individual component of TTCW were carefully defined. The optimal definition of TTCW may need to be varied in order to meet the differing needs of factors that include PAH cause, functional class, and age. The establishment of an independent and blinded committee who adjudicate problematic events (e.g. PAH-related hospitalization) in PAH trials using TTCW would further increase reliability, reducing intersite and interinvestigator variability.As the field continues to develop, overall trial design may warrant attention; to make results more clinically relevant, goal-orientated therapy strategies may be considered, in addition to traditional randomized controlled trial designs.