"The headline result is that MSers rate a delay in disease progression the most important outcome measures in relation to DMTs."
"The problem with disability progression in relatively short RRMS clinical trials is that the outcome measure is driven by relapses. Relapses change the EDSS in the short-term, which may not relate to long-term disability progression; I have said, on may occasions in the recent past, that the correlation between relapses and long-term outcome is very poor."
"How do relapses drive short-term disability progression? This occurs because of the way we analyse disability progression using a statistical technique called the survival curve. For example, if you have an EDSS of 2.0 and have a relapse that increases your EDSS to 4.0, and your EDSS stays at this level for 4 months before you recover over the next 6 months back to an EDSS of 2.0, you will defined in the trial as having progressed, simply because your EDSS increased by more than 1.0 point for longer than 3 months. Despite having no effect on the average EDSS scores across a population of MSers in clinical trials many DMTs claim to have an impact on disability progression simply because of this effect; this scenario happens because more relapses occur in trial subjects on placebo than on active treatment."
"This effect of relapses on the survival curve is a major confounder and is the reason why I believe that to claim that a particular drug has impact on disability progression it also need to impact on the average EDSS scores across the study and have an impact on objective MRI measures that we have linked to disease progression, for example brain atrophy. I am therefore very impressed that 38% of readers of this blog rated brain atrophy as the most important outcome measure for a DMT. I am not sure in myself that it should be rated this highly at this point in time, simply because we still have a lot for us to learn about its meaning and role in MS. Despite this brain atrophy does offer us a window into the brain and probably correlates with neuroprotective effects of DMTs. This is why DMTs that have a positive impact on brain atrophy are more-than-likely to have a positive impact on long-term disability progression, the outcome measure that is the most important to MSers."