Document Type

Article

Publication Date

7-1-2012

Comments

This article has been peer reviewed. It is the authors' final version prior to publication in Arthritis Care and Research

Volume 64, Issue 7, July 2012, Pages 945-954.

The published version is available at DOI: 10.1002/acr.21667. Copyright ©

Wiley-Blackwell

Abstract

The purpose of this manuscript is to discuss relevant aspects of clinical trials for Systemic Sclerosis (SSc) and to identify important considerations for the design of SSc disease modification clinical trials. Placebo randomized controlled trials with appropriate identification of SSc patients with diffuse progressive SSc skin involvement of recent onset, along with a rescue strategy for patients with worsening lung and skin involvement are suggested. If change in skin thickening is a major outcome of the study, the selection of patients with recent onset of disease and a predetermined degree of skin involvement are crucial requirements. The trial duration should be of at least 12 months. Sample size calculations should consider differences that exceed the Minimal Important Difference. Other relevant trial designs and potential threats to study validity are also discussed. Previous SSc-disease modifying trials have been beset by high dropout rates. Analyses on the subset of subjects completing the trial or applying the last observation- carried-forward approach can potentially lead to biased estimates and false conclusions. Strategies for retention of subjects should be included at the design stage and analyses to account for missing data should be performed.

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