Rationale and strategies for reevaluating the ACR20.

OBJECTIVE To assess whether the American College of Rheumatology response criteria ACR20 should be replaced by another definition of response with enhanced discriminant validity. METHODS We worked with statisticians to define over 100 different ways of defining response, including dichotomous definitions (e.g., ACR20; ACR50; ACR70; low disease activity), ordinal definitions (EULAR response; ACR20, ACR50, ACR70), disease activity indexes [Disease Activity Score (DAS); Disease Activity Index, SDAI], continuous definitions (mean percentage improvement in all core set measures; nACR, ACRn), and hybrid definitions (ACR20, ACR50, ACR70 defined for a patient as 0, 1, 2, 3 scale with continuous measures between intervals) along with variations on each of these approaches (e.g., percentage vs absolute change in DAS; e.g., measures requiring vs not requiring joint count improvement). To test clinical validity, we administered a survey using patients from a trial who had various levels of improvement and asked rheumatologists whether and by how much these patients improved. For Sn-to-Chge, we are collecting data from large disease modifying antirheumatic drug multicenter trials in rheumatoid arthritis and ranking candidate definitions of response on their average p values in distinguishing active treatment from placebo or combination compared to single comparator. RESULTS We surveyed 52 rheumatologists about which trial patients had improved and by how much. Trial data were obtained and tested for sensitivity to change. CONCLUSION A rigorous data-driven consensus process was used to reassess the ACR20.