Regression to the mean and predictors of MRI disease activity in RRMS placebo cohorts--is there a place for baseline-to-treatment studies in MS?

Abstract

BACKGROUND:

Gadolinium-enhancing (GD+) lesions and T2 lesions are MRI outcomes for phase-2 treatment trials in relapsing-remitting Multiple Sclerosis (RRMS). Little is known about predictors of lesion development and regression-to-the-mean, which is an important aspect in early baseline-to-treatment trials.

OBJECTIVES:

To quantify regression-to-the-mean and identify predictors of MRI lesion development in placebo cohorts.

METHODS:

21 Phase-2 and Phase-3 trials were identified by a systematic literature research. Random-effects meta-analyses were performed to estimate development of T2 and GD+ after 6 months (phase-2) or 2 years (phase-3). Predictors of lesion development were evaluated with mixed-effect meta-regression.

RESULTS:

The mean number of GD+-lesions per scan was similar after 6 months (1.19, 95%CI: 0.87-1.51) and 2 years (1.19, 95%CI: 1.00-1.39). 39% of the patients were without new T2-lesion after 6 month and 19% after 2 years (95%CI: 12-25%). Mean number of baseline GD+-lesions was the best predictor for new lesions after 6 months.

CONCLUSION:

Baseline GD-enhancing lesions predict evolution of Gd- and T2 lesions after 6 months and might be used to control for regression to the mean effects. Overall, proof-of-concept studies with a baseline to treatment design have to face a regression to 1.2 GD+lesions per scan within 6 months.

• Authors: Jan-Patrick Stellmann, Klarissa Hanja Stürner, Kim Lea Young, Susanne Siemonsen, Tim Friede, Christoph Heesen
• Journal: PloS one (PLoS One) Vol. 10 Issue 2 Pg. e0116559 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 25659100 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Contrast Media
• Gadolinium

Topics

• Clinical Trials, Phase II as Topic
• Clinical Trials, Phase III as Topic
• Contrast Media (therapeutic use)
• Female
• Gadolinium (therapeutic use)
• Humans
• Magnetic Resonance Imaging (methods)
• Male
• Multiple Sclerosis (diagnostic imaging, therapy)
• Radiography
• Randomized Controlled Trials as Topic