Objective. The objective was to describe the methodology used to develop new response criteria for adult DM/PM and JDM. Methods. Patient profiles from prospective natural history data and clinical trials were rated by myositis specialists to develop consensus gold-standard ratings of minimal, moderate and major improvement. Experts completed a survey regarding clinically meaningful improvement in the core set measures (CSM) and a conjoint-analysis survey (using 1000Minds software) to derive relative weights of CSM and candidate definitions. Six types of candidate definitions for response criteria were derived using survey results, logistic regression, conjoint analysis, application of conjoint-analysis weights to CSM and published definitions. Sensitivity, specificity and area under the curve were defined for candidate criteria using consensus patient profile data, and selected definitions were validated using clinical trial data. Results. Myositis specialists defined the degree of clinically meaningful improvement in CSM for minimal, moderate and major improvement. The conjoint-analysis survey established the relative weights of CSM, with muscle strength and Physician Global Activity as most important. Many candidate definitions showed excellent sensitivity, specificity and area under the curve in the consensus profiles. Trial validation showed that a number of candidate criteria differentiated between treatment groups. Top candidate criteria definitions were presented at the consensus conference. Conclusion. Consensus methodology, with definitions tested on patient profiles and validated using clinical trials, led to 18 definitions for adult PM/DM and 14 for JDM as excellent candidates for consideration in the final consensus on new response criteria for myositis.
Bibliographical noteFunding Information:
We thank Saad Feroz for assistance in drafting candidate definitions for response criteria and developing patient profiles. We thank the following people for invaluable input and feedback on project development and support: B.M.F., American College of Rheumatology; Daniel Aletaha, European League Against Rheumatism; Suzette Peng and Sarah Yim, the US Food and Drug Administration; Thorsten Vetter and Richard Vesely, European Medicines Agency; Bob Goldberg and Theresa Curry, The Myositis Association; Rhonda McKeever and Patti Lawler, Cure JM Foundation; and Irene Oakley, Myositis UK. We thank Drs Michael Ward and Steven Pavletic for critical reading of the manuscript. P.H. owns the 1000Minds software referred to in this article, which he co-invented with Franz Ombler. J.V.'s work in myositis is supported by the project (Ministry of Health, Czech Republic) for conceptual development of research organization 00023728 (Institute of Rheumatology). H.C. is supported by an Arthritis Research UK (18474) and the National Institute for Health Research Biomedical Research Unit Funding Scheme.This work was supported in part by the ACR, the EULAR, the intramural research programme of the National Institutes of Health, National Institute of Environmental Health Sciences, the National Center for Advancing Translational Sciences and the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Istituto Giannina Gaslini Genova (Italy) and the Paediatric Rheumatology International Trials Organisation (PRINTO), Cure JM Foundation, Myositis UK and The Myositis Association.
- 1000Minds software
- Conjoint analysis
- Hybrid measure
- Juvenile dermatomyositis
- Outcome assessment
- Response criteria