Evaluation of Test Characteristics for Outcome Measures Used in Raynaud's Phenomenon Clinical Trials

Authors

  • Heather Gladue,

    1. University of Michigan Scleroderma Program, Ann Arbor
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  • Paul Maranian,

    1. David Geffen School of Medicine at University of California, Los Angeles
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  • Harold E. Paulus,

    1. David Geffen School of Medicine at University of California, Los Angeles
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  • Dinesh Khanna

    Corresponding author
    1. University of Michigan Scleroderma Program, Ann Arbor
    • University of Michigan Scleroderma Program, Division of Rheumatology/Department of Internal Medicine, Suite 7C27, 300 North Ingalls Street, SPC 5422, Ann Arbor, MI 48109
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    • Dr. Khanna has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Actelion, Gilead, Bayer, Pfizer, Digna, United Therapeutics, Roche, and Sanofi-Aventis.


Abstract

Objective

Randomized controlled trials (RCTs) in Raynaud's phenomenon (RP) have shown conflicting efficacy data. Also, there is no consensus on the outcome measures that should be used. Our objectives were to assess the reliability of individual core set measures used in 3 RCTs, evaluate the placebo response for individual core set measures, and determine if a composite of individual core set measures will decrease the placebo response, which may improve our ability to see treatment effects in future trials.

Methods

We analyzed core set measures from 249 patients in the placebo-treated groups from 3 RCTs. Core set measures analyzed included the Raynaud's Condition Score (RCS); patient and physician assessment of RP; pain, numbness, and tingling during an RP attack; average number of attacks/day; and duration of attacks. Intraclass correlation coefficients (ICCs) were calculated during the run-in period to the RCTs.

Results

ICCs of ≥0.70 were observed for the RCS, attack symptoms, and average attacks/day. A high placebo response rate was observed for all individual core measures except the duration of attacks. For the RCS, the placebo response ranged from 56% with ≥10% improvement to 19.5% with ≥60% improvement. In contrast, placebo response rates of 10–20% were observed when several core set measures were combined to develop a composite score.

Conclusion

Outcome measures used in RCTs of RP are associated with marked variability. A combination of outcome measures is associated with low placebo responses. Future studies are needed to assess if a composite score will be able to differentiate placebo from an effective agent.

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