Our final analysis on MS

Increasing the power of MS clinical trials

By Jacob Elkins, M.D.
Senior Director, Clinical Development

April 18, 2016

As a physician-scientist, I have first-hand experience in how difficult it can be to truly assess treatment efficacy. The weight and importance of clinical trials and whether a drug or treatment makes it to the market, relies on how we interpret our results. At Biogen, I work closely with Katherine Reister, a biostatistician, on developing new methods to improve data analysis in clinical trials.

A new look at the data
Kathy and I realized that measuring disability progression in multiple sclerosis (MS) clinical trials may be biased by patients dropping out of trials after an initial decline in their disability scores; they may feel that the treatment is not working for them and see no reason to continue their participation. This introduces consequences for assessing how well a trial performs. We therefore set out to develop new analysis methods that they would be less vulnerable to this bias and potentially improve our ability to determine how well an MS treatment is working.

MS disability is typically assessed by an initial visit to identify a worsening of symptoms. A patient then returns 3-6 months later for confirmation. The gold standard for diagnosing a patient with MS is confirmed disability progression (CDP), which is the combination of objective assessments by a neurologic examiner (i.e., measurement of weakness and difficulty walking). CDP is an important and commonly used measure of evaluating how a treatment is working and provides immense value and information.

Improving CDP measurement
During an MS clinical trial, if a patient drops out after a decline in their disability but before the confirmatory visit, their data typically does not inform the analysis of disability. Furthermore, if patients continue to decline or improve after confirmed disability progression occurs, this information is also not included in the analysis of the treatment effect. Perhaps this is based on the assumption that CDP is irreversible: once you have confirmed disability progression, you won’t get better. We now know this is untrue, and some patients return to baseline whereas others continue to decline. Trial analysis has not adjusted for this. It’s therefore essential that we consider ways to analyze disability progression that makes a more complete use of the information we gather in our trials.

Increasing the power of MS clinical trials
CDP is widely used and accepted within the medical community, so Kathy and I decided to adjust the way we analyze clinical trial data to extract more and better information. Our team at Biogen recently demonstrated that when evaluating treatment effects in an MS trial, it is important to consider loss of follow-up on patients who have dropped out before their confirmed diagnosis. By analyzing data from these patients, we were able to assess a risk estimate for confirmed disease progression diagnosis, had they remained in the trial.

With our new approach, we believe that we can provide a more accurate estimation of how well a treatment is working. In addition, by improving the way we analyze clinical trial data, we have the potential to increase the power of clinical trials and reduce their costs so that the barriers to bringing new medicines to patients can be reduced.

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