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.
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.
Authors: Natalie A Schwehr; Karen M Kuntz; Mary Butler; Eva A Enns; Nathan D Shippee; Elaine Kingwell; Helen Tremlett; Adam F Carpenter Journal: Mult Scler Date: 2019-07-29 Impact factor: 6.312
Authors: Thomas Lehnert; Christian Röver; Sascha Köpke; Jordi Rio; Declan Chard; Andrea V Fittipaldo; Tim Friede; Christoph Heesen; Anne C Rahn Journal: Syst Rev Date: 2022-07-01
Authors: Ludwig Kappos; Gilles Edan; Mark S Freedman; Xavier Montalbán; Hans-Peter Hartung; Bernhard Hemmer; Edward J Fox; Frederik Barkhof; Sven Schippling; Andrea Schulze; Dirk Pleimes; Christoph Pohl; Rupert Sandbrink; Gustavo Suarez; Eva-Maria Wicklein Journal: Neurology Date: 2016-08-10 Impact factor: 9.910
Authors: Bruce Ac Cree; Jeffrey A Cohen; Anthony T Reder; Davorka Tomic; Diego Silva; Daniela Piani Meier; Annik K Laflamme; Shannon Ritter; David Leppert; Ludwig Kappos Journal: Mult Scler Date: 2021-03-26 Impact factor: 6.312