An Introduction to the Analysis and Interpretation of Radiographic Data from Rheumatoid Arthritis Clinical Trials

• Activity Number: 368
• Type: Topic Contributed
• Date/Time: Wednesday, August 11, 2004 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): James Whitmore*+ and Guowen (Gordon) Sun and Wayne Tsuji
• Companies: Amgen, Inc. and Amgen, Inc. and Amgen, Inc.
• Keywords: clinical trials ; rheumatoid arthritis ; radiographic data

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease that often results in progressive loss of function in affected joints. Serial x-ray films reveal the joint erosions and progressive joint space narrowing that characterize RA. Validated radiographic indices have been developed, with progression generally assessed over periods of at least 12 months. Slowing radiographic progression has become an established surrogate marker for overall patient benefit. Advances in RA treatment have led to therapies that may inhibit the progression of structural damage. The analysis and interpretation of the radiographic data from clinical trials of these therapies is complicated by missing data, inter- and intra-reader variability, and the highly skewed distribution of change. Further, placebo treatment arms may be unethical in these studies, leading to active comparators for which historical data on radiographic progression versus untreated patients is scant. This paper will provide an overview of the rationale and methods for characterization of progression and illustrate statistical issues in the analysis of radiographic data from RA clinical trials.