title: Clinical Trial Design Issues in Systemic Sclerosis: an Update.
abstract: Systemic sclerosis (scleroderma, SSc) is a multisystem disease characterized by vasculopathy, autoimmunity, and fibrosis. SSc has the highest disease-related mortality rate among the rheumatologic illnesses. In the USA, there remains no FDA-approved therapy. As our understanding of SSc pathogenesis improves, targeted therapies interrupting key pathways and mediators will be studied in clinical trials. However, clinical trials in SSc are fraught with challenges. Validated clinical outcome measures do not exist for all disease manifestations. It can be difficult to discern disease activity from damage. SSc is highly heterogeneous, with multiple different phenotypes, and predicting who will have progressive disease is not currently well understood. Biomarkers are in early stages of development and do not represent surrogate outcomes at this time. Given that SSc is uncommon, studies of similar disease aspects or populations can lead to competition for patients. This review will focus on current issues in SSc clinical trial design.
authors.affiliation: Hospital for Special Surgery, 535 East 70th Street, New York, NY, 10021, USA. gordonj@hss.edu.
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Gordon
authors.affiliation: University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Robyn T
authors.initials: RT
authors.lastname: Domsic
mesh_terms: D015415:Biomarkers / Q000097:blood; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D017063:Outcome Assessment, Health Care / Q000379:methods; D018579:Patient Selection; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design; D012595:Scleroderma, Systemic / Q000175:diagnosis / Q000188:drug therapy*
chemical_list: D015415:Biomarkers
keywords: Clinical trial design; Scleroderma; Systemic sclerosis