Dropping relapse rates

#MSBlog: were have all the relapses gone?

Epub: Steinvorth et al. Explaining temporal trends in annualised relapse rates in placebo groups of randomised controlled trials in relapsing multiple sclerosis: systematic review and meta-regression Mult Scler. 2013 Mar.

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: These investigators 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: They identified 56 studies. MSers 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.


"The drop in relapse rates are being driven by several factors: 

(1) the change in definition of MS with the adoption of the McDonal criteria - this is called the Will Rogers Effect.
(2) less active MSers are being recruited to trials; the most active MSers are already on treatment or are reluctant to volunteer for a placebo-controlled trials. 
(3) relapses are now defined using quite strict definitions; did you know about 50% of relapses that occurin contemporary trials don't fulfill the protocol-defined criteria for a relapse.
(4) finally the natural history of MS may be changing; i.e. becoming more benign. 

All this means that when we do trials now we need many more MSers to participate to get a definitive answer." 

Labels: