Trial design: how must we move ahead?
Scleroderma is clinically heterogeneous and a variety of plausible mechanisms of disease have been hypothesized. Recent years have witnessed a significant improvement in overall survival although all of the gains in management have been therapies for specific organ involvement, e.g. renal crisis and pulmonary arterial hypertension. Future studies will rely on improved clinical science, which involves structured validation of proposed measures of outcome; development of a combined response index; and further refinement of specific subsets of disease expression. Immunoablation with stem cell reconstitution is an example of aggressive therapy chosen as appropriate for a particularly severe disease subset and in whom the pilot data are encouraging. Good science and clinical ethics force continued consideration of equipoise between risk and benefit.
Seibold
J R
JR
University of Michigan Scleroderma Program, Ann Arbor, Michigan 48106, USA. jseibold@umich.edu
Tyndall
A
A
Furst
D E
DE
D002986:Clinical Trials as Topic / Q000592:standards*; D006801:Humans; D012107:Research Design; D018570:Risk Assessment; D012595:Scleroderma, Systemic / Q000628:therapy*; D016896:Treatment Outcome
Ann Rheum Dis. 2008 May;67(5):703-9
17893248
Arthritis Rheum. 2006 Dec;54(12):3962-70
17133610
Blood. 2007 Aug 15;110(4):1388-96
17452515
Ann Rheum Dis. 2007 Jul;66(7):940-4
17329309
Am J Respir Crit Care Med. 2007 Nov 15;176(10):1026-34
17717203
N Engl J Med. 2006 Jun 22;354(25):2655-66
16790698