Placebo response in Raynaud's Phenomenon clinical trials: The prominent role of regression towards the mean: Placebo response in Raynaud's Phenomenon.

Autor: Roustit M; Univ. Grenoble Alpes, Inserm U1300, 38000 Grenoble, France; Univ. Grenoble Alpes, Inserm CIC 1406, CHU Grenoble Alpes, 38000 Grenoble, France. Electronic address: MRoustit@chu-grenoble.fr., Jullien A; Univ. Grenoble Alpes, Inserm CIC 1406, CHU Grenoble Alpes, 38000 Grenoble, France., Jambon-Barbara C; Univ. Grenoble Alpes, Inserm CIC 1406, CHU Grenoble Alpes, 38000 Grenoble, France., Goudon H; Univ. Grenoble Alpes, Inserm CIC 1406, CHU Grenoble Alpes, 38000 Grenoble, France., Blaise S; Univ. Grenoble Alpes, Inserm U1300, 38000 Grenoble, France; Department of Vascular Medicine, CHU Grenoble Alpes, 38000 Grenoble, France., Cracowski JL; Univ. Grenoble Alpes, Inserm U1300, 38000 Grenoble, France; Univ. Grenoble Alpes, Inserm CIC 1406, CHU Grenoble Alpes, 38000 Grenoble, France., Khouri C; Univ. Grenoble Alpes, Inserm U1300, 38000 Grenoble, France; Univ. Grenoble Alpes, Inserm CIC 1406, CHU Grenoble Alpes, 38000 Grenoble, France.
Jazyk: angličtina
Zdroj: Seminars in arthritis and rheumatism [Semin Arthritis Rheum] 2022 Dec; Vol. 57, pp. 152087. Date of Electronic Publication: 2022 Aug 27.
DOI: 10.1016/j.semarthrit.2022.152087
Abstrakt: Background: Substantial placebo response has been observed in trials assessing treatments in Raynaud's Phenomenon (RP), which makes any treatment effect difficult to detect. However, whether this response is due to a real placebo effect or to other nonspecific effects, such as regression towards the mean (RTM), has not been explored. Our objectives were to explore and quantify placebo response in RP, and to evaluate the magnitude of RTM contribution.
Methods: We combined trial-level and individual-level data from a series of n-of-1 trials and a network meta-analysis, respectively. Main outcomes were the daily frequency and the mean duration of RP attacks, as well as the Raynaud's Condition Score (RCS). We estimated the placebo response by the mean difference between the placebo period (or arm) and the baseline. RTM was estimated by the relationship between placebo response and baseline, and with Galton squeeze plots. Finally, we simulated the effect of the threshold used for inclusion in clinical trials on RTM.
Findings: We observed a large and significant placebo response from both individual and trial data for RCS [-1.20 (-1.63, -0.77) and -0.65 (-0.89, -0.41)] and the daily frequency of RP [-0.61 (-0.85, -0.37) and -0.75 (-0.95, -0.54)]. Outcome at baseline was significantly associated with placebo response, suggesting the presence of RTM. The latter was confirmed on individual data, through Galton squeeze plots.
Interpretation: Placebo response is large in RP trials, and likely due to regression towards the mean rather than 'true' placebo effect. This should be carefully considered when designing future trials.
Funding: This work has been partially supported by MIAI @ Grenoble Alpes (ANR-19-P3IA-0003).
Competing Interests: Declaration of Competing Interest The authors declare no competing interest for this work.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: