What’s in a multiple sclerosis study?
A backgrounder on the COPAXONE® 2-year pivotal trial1
During 1991-1992, 251 people with relapsing-remitting multiple sclerosis (RRMS) took part in a pivotal trial to determine the effectiveness of COPAXONE®. This was a double-blind, randomized, multicenter, placebo-controlled trial with a study duration of 2 years. These study design characteristics are considered the most reliable form of scientific evidence. The primary endpoint (or goal) for this main, or “pivotal” trial, was to measure the effect COPAXONE® had on relapses.
In addition to relapse reduction, there were secondary endpoints that looked at the impact of COPAXONE® over time. This impact can be measured by the EDSS, or the Expanded Disability Status Scale. The EDSS measures changes in a person’s physical ability on a scale beginning with 0.0 and worsening to a level of 10.0. People with an EDSS level of 0.0 to 5.0 were included in the pivotal trial.
This “Class I” trial led to the approval of COPAXONE® by the FDA in 1996. See results of the pivotal trial.
Double-blind: Double-blind describes a strict way of conducting a clinical trial. This method should reduce the possibility of bias (unfair influence) on the part of both participants and health care providers. In this type of trial, health care providers and participants are “blinded.” This means that neither knows what drug regimen the participant is taking. In the COPAXONE® pivotal trial, neither the health care providers nor the participants were aware of whether the participant was taking COPAXONE® or an inactive substance called a placebo.
Randomized: A randomized controlled trial is a type of clinical trial used to test the effectiveness of medicines. Participants are randomly chosen to take either one drug regimen or another. This method reduces many of the biases that can negatively affect the validity of medical research. For the COPAXONE® pivotal trial, 251 people with RRMS were randomly chosen to take either COPAXONE® (125 people) or an inactive substance called placebo (126 people).
Multicenter: A clinical trial that takes place at more than 1 medical center or clinic. The benefits of multicenter trials include a larger number of participants, different geographic locations, various ethnic groups, and the ability to compare results among the different centers—all of which help remove bias from the study. COPAXONE® was studied in 11 university centers across the country to help ensure that the trial was representative of a US RRMS population.
Placebo-controlled: This study method compares people taking a drug with people taking placebo. A placebo is an inactive substance which helps to determine the effectiveness of a drug by giving researchers something to compare the active drug to.
Study duration: The agreed-upon length of time during which results are collected. The study duration for the COPAXONE® pivotal trial was 2 years. Since people in this trial started at different times (staggered enrollment), the trial lasted 35 months to get 2-year’s worth of results for all participants. The average (mean) time people were on treatment was 30 months.
Primary endpoint: A primary endpoint is the main goal of a clinical trial. This goal must be met for the trial to be considered successful. The primary endpoint for the COPAXONE® pivotal trial was the reduction in the frequency of relapses.1 This was measured by calculating the difference between the number of relapses in people taking COPAXONE® compared with those taking placebo, an inactive substance, over the 2-year period. This result is known as the mean (or average) relapse rate.
Secondary endpoints: Secondary endpoints are other important ways to measure efficacy or safety in a clinical trial. The secondary endpoints for the COPAXONE® pivotal trial included1:
- Changes in EDSS from the beginning of the study (baseline) to the end, measured and organized using the following standards:
- "Improved" (a reduction of at least 1 step on the EDSS scale)
- "Stabilized" (no change in EDSS or change of less than 1 step)
- "Worsened" (an increase of more than 1 step on the EDSS scale)
- Percentage of participants with “sustained disease progression.” This was defined as an increase of more than 1 step on the EDSS scale that needs to have lasted for at least 3 months
Note: The COPAXONE® pivotal trial was not designed ("powered") to be able to include the secondary endpoints, such as EDSS, as part of the formal approval (or indication) by the FDA.
EDSS: The Expanded Disability Status Scale is one of the most widely used rating systems for determining the ability level of people with MS. The EDSS measures changes in a person’s physical ability in one-half step increments on a scale beginning with 0.0 and worsening to a level of 10.0. People with an EDSS level of 0.0 to 5.0 were included in the pivotal trial. Here are some of the scores from the EDSS and what they represent:
The labeling for COPAXONE® does not include an indication for slowing the progression of disability.
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