Systemic sclerosis (scleroderma, SSc) is a rare, multisystem disease with features of autoimmunity, inflammation, and fibrosis that leads to organ- and life-threatening complications. SSc has the highest case fatality of any rheumatic disease and there are no therapies for the management of SSc approved by the United States Food and Drug Administration (FDA). A 2015 Roundtable meeting at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) focused on unmet research needs in scleroderma. A major conclusion from the Roundtable was the need to move beyond having outcome measure for each manifestation of SSc for use in clinical research to arriving at a set of validated outcome tools meeting the high standards and specific requirements of the FDA. Specifically, the scleroderma research community was challenged with working towards a White Paper, defined as a document that carefully evaluates the current status of outcome measures and trial design in SSc and to provide direction on outcome measures for clinical trials with a future goal to develop an FDA Draft Guidance Document. In this R13 conference grant, we propose to develop a White Paper on outcome measures for use in clinical trials in SSc, with a focus on measures that meet the FDA mandate on a how a patient feels, functions, and survives. We seek support for this process, the critical element of which is to hold a 2-day, in-person meeting to bring together all the key stakeholders in this disease space and finalize the outcomes for inclusion in the White Paper. The focus of the work is on outcomes likely acceptable to the FDA for clinical trials designed to support regulatory approval of new drugs for the treatment of SSc. The White Paper will be drafted by a group representing the key stakeholders related to this topic, including informed investigators, patient partners, patient advocacy groups, representatives of the biopharmaceutical industry, and representatives from the FDA. This project will be co-sponsored by the Scleroderma Clinical Trials Consortium, the major international, investigator-led group focused on the science and implementation of trials in SSc.
Our Specific Aims i nclude the following: 1) Organize an extended study team of stakeholders to work through focused task forces to propose outcomes suitable for use in trials in the main areas of disease impact in SSc; 2) Hold a 2-day in-person meeting that brings together leaders of the task forces, patients, patient advocacy groups, industry representatives, FDA officials, and expert consultants to arrive at a final set of outcomes appropriate for inclusion in a White Paper, and; 3) Disseminate results and conclusions that include preparing a manuscript of conference proceedings and presentation(s) at national and international rheumatology meetings.
(Public Health Relevance) Systemic sclerosis (scleroderma, SSc) is a rare, multisystem autoimmune disease that has the highest case fatality among rheumatic diseases and for which there are no FDA-approved management therapies. In this proposed conference grant, we plan to develop a ?White Paper? on outcomes measures for use in scleroderma clinical trials, with a focus on measures that meet the FDA mandate on a how a patient feels, functions, and survives. We seek support for this process, the critical element of which is to hold a 2-day, in- person meeting to bring together all the key stakeholders in this disease space and finalize the outcomes for inclusion in a White Paper that we believe will propel drug development in scleroderma and serve as a template for a future Draft Guidance Document by the FDA.
