Sunday, 17 March 2013

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." 


  1. Could it also be that more MSers supplement VitD? Or does the trial designs allow for this?

  2. Is it ethical to run placebo controlled trials rather than standard of care for RRMS?

    1. I agree there are now drugs available for RRMS, and so the controls will need to be on standard care. At moment companies are taking on the interferons as it usually gives them a marketing advantage when the drugs are shown to work better. Once one of the more effective DMT becomes standard care it will be hard to show better efficacy.

  3. This post is such pr0-DMT propaganda.

    1. We are pro DMT because they have positive effects on clinical course, it is not propoganda


Please note that all comments are moderated and any personal or marketing-related submissions will not be shown.