Defining appropriate outcome measures in pulmonary arterial hypertension related to systemic sclerosis: A Delphi consensus study with cluster analysis

Abstract

Objective. Outcome measures for pulmonary arterial hypertension associated with systemic sclerosis (PAH-SSc) are only partially validated. The aim of the present study was to establish an expert consensus regarding which outcome measures are most appropriate for clinical trials in PAH-SSc. Methods. Sixty-nine PAH-SSc experts (rheumatologists, cardiologists, pulmonologists) rated a list of disease domains and measurement tools in an Internet-based 3-stage Delphi consensus study. In stages 2 and 3, the medians of domains and measurement tools and frequency distributions of ratings, along with requests for re-ratings, were distributed to respondents to provide feedback. A final score of items was identified by means of cluster analysis. Results. The experts judged the following domains and tools as most appropriate for randomized controlled trials in PAH-SSc: lung vascular/pulmonary arterial pressure and cardiac function both measured by right heart catheterization and echocardiography, exercise testing measured by 6-minute walking test and oxygen saturation at exercise, severity of dyspnea measured on a visual analog scale, discontinuation of treatment measured by (serious) adverse events, quality of life/activities of daily living measured by the Short Form 36 and Health Assessment Questionnaire disability index, and global state assessed by physician measured by survival. Conclusion. Among experts in PAH-SSc, a core set of outcome measures has been defined for clinical trials by Delphi consensus methods. Although these outcome measures are recommended by this expert group to be used as an interim tool, it will be necessary to formally validate the present measures, as well as potential research measures, in further studies.

Systemic Sclerosis-Associated Pulmonary Arterial Hypertension

“…For the reasons mentioned above, alternative strategies are required to measure and compare the relative effects of available treatments in SSc-PAH. A call for noninvasive and clinically relevant markers of disease severity has been made and some are already currently tested (85).…”

Echocardiography as an Outcome Measure in Scleroderma-related Pulmonary Arterial Hypertension: A Systematic Literature Analysis by the EPOSS Group

“…SSc (EPOSS) utilizing a Delphi process among 74 interdisciplinary experts [8], only right heart catheterization (RHC) has so far been considered validated according to the "OMERACT filter criteria" and therefore judged "ready for use in clinical trials" [9].…”

“…Studies including < 5 PAH/PH-SSc patients and those for which there was no information given as to whether any PAH/PH-SSc patients were analyzed, were also excluded. Studies concerning exercise echo were also not considered for the analysis, because exercise echo was not part of the core set recommended by the EPOSS group after the Delphi exercise [8].…”

“…Echocardiography was selected by the experts during the recent Delphi study [8] as an appropriate measure for the evaluation of PAP, heart structure and function in PAH-SSc patients. Thus, by definition, it was considered credible (having face validity).…”

“…Face validity is the only OMERACT criterion that is fully validated based on the consensus of experts who selected echo as an appropriate outcome measure for evaluation of PAH-SSc [8] as well as based on its frequent use as an evaluation tool in PAH/PH-SSc studies. There are no further studies required.…”