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 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 3 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.
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