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arXiv · 1303.2803

Explaining temporal trends in annualized relapse rates in placebo groups of randomized controlled trials in relapsing multiple sclerosis: systematic review and meta-regression

Simon M. Steinvorth·Christian Röver·Simon Schneider·Richard Nicholas·Sebastian Straube·Tim Friede
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Abstract

Background: Recent studies have shown a decrease in annualised relapse rates (ARRs) in placebo groups of randomised controlled trials (RCTs) in relapsing multiple sclerosis (RMS). Methods: We conducted a systematic literature search of RCTs in RMS. Data on eligibility criteria and baseline characteristics were extracted and tested for significant trends over time. A meta-regression was conducted to estimate their contribution to the decrease of trial ARRs over time. Results: We identified 56 studies. Patient age at baseline (p < 0.001), mean duration of multiple sclerosis (MS) at baseline (p = 0.048), size of treatment groups (p = 0.003), Oxford Quality Scale scores (p = 0.021), and the number of eligibility criteria (p<0.001) increased significantly, whereas pre-trial ARR (p = 0.001), the time span over which pre-trial ARR was calculated (p < 0.001), and the duration of placebo-controlled follow-up (p = 0.006) decreased significantly over time. In meta-regression of trial placebo ARR, the temporal trend was found to be insignificant, with major factors explaining the variation: pre-trial ARR, the number of years used to calculate pre-trial ARR and study duration. Conclusion: The observed decline in trial ARRs may result from decreasing pre-trial ARRs and a shorter time period over which pre-trial ARRs were calculated. Increasing patient age and duration of illness may also contribute.

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Simon M. Steinvorth, Christian Röver, Simon Schneider, Richard Nicholas, Sebastian Straube, Tim Friede. 2014-03-17. Explaining temporal trends in annualized relapse rates in placebo groups of randomized controlled trials in relapsing multiple sclerosis: systematic review and meta-regression. https://doi.org/10.1177/1352458513481009

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