Shorter trials?

Epub: Wang et al. Short-Term Relapse Quantitation as a Fully Surrogate Endpoint for Long-Term Sustained Progression of Disability in RRMS Patients Treated with Natalizumab.Neurol Res Int. 2011:195831

Time to sustained worsening in the expanded disability status scale (EDSS) as the standard for evaluating the accumulation of disability has been used as a measure of clinical efficacy in many relapsing-remitting multiple sclerosis (RRMS) clinical trials. However, this measurement usually requires a large sample and long-term study to demonstrate the treatment effect.

Annualized relapse rate or time to first relapse is also widely used as alternative measurements of clinical efficacy. A formal statistical validation of short-term relapse activity as a surrogate endpoint for long-term sustained progression of disability could potentially permit smaller, shorter, and less expensive clinical trials in RRMS. Four statistical validation/evaluation approaches consistently showed that relapse activity through one year of treatment serves as statistically valid surrogate endpoint for time to sustained progression of disability. The analysis demonstrates that long-term sustained progression of disability can be predicted by short-term relapse measures with 4 consistent validations of statistical approaches, including a formal statistical hypothesis test.

This was demonstrated in a large phase III trial of natalizumab and showed that the beneficial clinical effect of natalizumab on sustained progression of disability at 2 years in patients with RRMS can be predicted by the total number of relapses at 1 year.

CoI: This study was undertaken by Biogen.

“What this study shows is that events in the first 12 months of a clinical trial predict what is going to happen at the end of the study and possibly beyond. I am aware of data sets beyond this data that show the same thing. I think this is valid and may be it is time for the regulators (FDA and EMA) to accept short-term surrogates to help speed-up drug development. The problem with this approach it won’t allow sufficient data to be collected to make a judgement on safety.”

One thought on “Shorter trials?”

  1. I am finding it challenging to understand the Chart above.What is the average differential in prognosis (as expressed in EDSS) for someone who relapsed in the first year on Tysabri v.s. someone who has not?Thank you

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