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

Abstract

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). 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. 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). 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.