Guidelines for clinical trials in systemic sclerosis (scleroderma)

Abstract

Objective. To develop guidelines for therapeutic trials designed to improve the overall course of systemic sclerosis (SSc), that is, to reduce the development of significant organ damage or death.Methods. A committee developed general guidelines for patient inclusion and exclusion criteria, randomization, blinding of patients and physicians, controls, duration of the trial, investigator training, responses, samples size, study dropouts, statistical analyses, data management, and safety monitoring. Delphi and nominal group techniques were used.Results. Briefly, patients with diffuse cutaneous SSc of less than 24 months' duration should be included

Recombinant human anti–transforming growth factor β1 antibody therapy in systemic sclerosis: A multicenter, randomized, placebo‐controlled phase I/II trial of CAT‐192

“…Previous studies yielding negative results have hampered the development of validated assessment tools that are sensitive to change over the time course of a therapeutic clinical trial. There is continued interest in this area, and several groups of investigators have reported guidelines for disease assessment and for the performance of clinical trials (16,17,31). At present, for a short-term study, the MRSS remains the most frequently used tool for the assessment of skin sclerosis.…”

“…To enrich the study cohort for patients in the progressive phase of dcSSc, the following inclusion criteria were 324 DENTON ET AL required for any study subject: enrollment within 18 months of the onset of their disease (defined as the time from the first non-Raynaud's phenomenon manifestation); a modified Rodnan skin thickness score (MRSS) between 10 and 28 (inclusive); and evidence of worsening disease by any of the following 3 criteria: progression of skin disease to a new skin score site within the previous 3 months; an increase in the skin score from 1 to 3 at any skin score location; or the presence of tendon friction rubs at 3 or more joints (16). The clinical features of the study cohort are given in Table 2.…”

“…The 17-site MRSS was used, with each site assessed by global average integer scoring (0-3 scale). Consistent with clinical trial guidelines (16,17), and to minimize interobserver variation, all investigators attended skin scoring standardization sessions, since earlier studies suggest that this reduces interindividual variability in skin scoring (18). Renal function was determined by serum creatinine and creatinine clearance values.…”

Production of type 2 cytokines by CD8+ lung cells is associated with greater decline in pulmonary function in patients with systemic sclerosis

“…Diffuse cutaneous SSc was defined as skin involvement on the extremities proximal to the elbows or knees, or truncal involvement. Disease onset was defined as the time of the first symptom clearly attributable to SSc, which included Raynaud's phenomenon (22).…”

Improvement in skin thickening in systemic sclerosis associated with improved survival

“…Many reports have attributed improvement in skin thickening to certain medications, but controlled trials have not confirmed these observational studies (8,9). Several problems have made clinical therapeutic trials in scleroderma particularly difficult to perform and interpret, although recent guidelines for the treatment of scleroderma have been made by a National Institutes of Health panel (10). Great variability in the disease makes it hard to identify an adequate number of patients with similar disease features.…”