Development and Initial Validation of the Novel Scleroderma Clinical Trials Consortium Activity Index.

ABSTRACT

OBJECTIVE: Accurate measurement of disease activity in systemic sclerosis (SSc) remains a significant clinical challenge. The Scleroderma Clinical Trials Consortium (SCTC) convened an Activity Index (AI) Working Group (WG) to develop a novel measure of disease activity (SCTC-AI). METHODS: Using consensus methodology, we developed a conceptual definition of disease activity. Literature review and expert consensus generated provisional SCTC-AI items, which were reduced by Delphi survey. Provisional items were weighted against a combined endpoint of morbidity and mortality, using time-dependent Cox proportional hazards regression analysis of the Australian Scleroderma Cohort Study (ASCS) (n = 1,254). External validation of the SCTC-AI was performed using data collected from 1,103 Canadian Scleroderma Research Group Study participants. RESULTS: Disease activity in SSc was defined using consensus methodology as "aspects of disease that are reversible, or can be arrested, with time and, or effective therapy." One-hundred and forty-one provisional SCTC-AI items were generated and reduced using three rounds of Delphi survey and statistical reduction and weighting, against mortality and quality of life measures, yielding a final 24-item index with a maximum possible score of 140. Survival analysis in an external cohort showed a graded relationship between disease activity scores and survival (P < 0.01). CONCLUSION: We present a novel instrument to quantify the burden of disease activity in SSc. We have employed a rigorous consensus-based process in combination with data-driven methods to develop an instrument that has face, content, and criterion validity. Further work is required to fully validate and confirm the construct and discriminative validity of the SCTC-AI.