New method may be better at measuring disability improvement

A new statistical method could help to more accurately capture changes in disability severity for people with multiple sclerosis (MS) and monitor the impact of MS treatments.

“With the use of this new statistical methodology, it is possible to estimate the time to improvement as well as the duration of improvement, information that is better suited to describing a non-final outcome like disability improvement,” researchers wrote.

The study, “Assessing the Duration of EDSS Improvement After a Therapy Start: A Novel Approach Applied to the Long-Term Extension of the PRISMS Study,” was published in Multiple Sclerosis and Related Disorders.

Expanded Disability Status Scale commonly used to track disability

Multiple sclerosis causes many symptoms that can be disabling, leading to challenges in day-to-day life. To track disability in MS, researchers commonly use the Expanded Disability Status Scale, which is a rating from 0 to 10 where higher scores reflect greater disability.

Measuring changes on the EDSS is one of the main tools that scientists use in clinical trials to test new therapies for MS. Typically, trials will look at the number of patients who experienced an improvement in EDSS, as well as the number who experienced a worsening in this score.

In the new study, scientists argue that this analysis method fails to capture the experience of disability in MS.

The problem, according to the researchers, is that these methods don’t adequately account for the fact that disability status can change over time, even after initial improvement. As an example, if one patient experiences an improvement in EDSS scores that lasts only a few months, but another patient has improvements that last several years, traditional methods would simply count both patients as having “improved,” without any distinctions based on how long the improvement lasted.

“This method of measuring disability improvement does not necessarily take into account the transitory nature of the improvement in a chronic and progressive condition such as MS,” the researchers wrote.

The prevalence estimator was found to be more powerful at identifying a treatment impact than an improvement in EDSS alone.

In this study, the scientists used a different method where they instead estimated the prevalence of improvement. In simple terms, this method involves looking at EDSS scores based on a single point in time (e.g., the end of a study). If EDSS scores are better at the time of assessment than at the start of the study, then the patient is labeled as “improved.” If the patient had experienced some earlier improvement, but EDSS scores then worsened again, the patient isn’t counted as having improved.

To illustrate the usefulness of this method, the researchers conducted an analysis of data from more than 500 people with MS who participated in PRISMS, a clinical trial conducted in the 1990s that helped support the approval of the MS therapy Rebif (interferon beta-1a).

At the start of the trial, patients were randomly assigned to one of three groups: a low dose of Rebif, a high dose of Rebif, or a placebo. After the two-year placebo-controlled portion of the study, patients originally on placebo were switched to Rebif treatment.

Using standard methods, the rate of improvement in EDSS score after several years of follow-up was similar in all three groups, with just over 20% of patients experiencing any documented improvement in disability scores that was confirmed six months later.

“More than 20% of patients who were initially assigned to one of the three treatment groups were estimated to have experienced at least one confirmed improvement event over the course of seven years. This cumulative incidence of improvement does not take into account how long this improvement might last,” the researchers wrote.

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Prevalence method shows clear distinction between dose groups after follow-up

However, using the prevalence method, there was a clear distinction between groups after three years of follow-up: 15.4% of patients in the high-dose group showed improvement, compared with 11.3% of those on the low dose and 10.1% of those originally on a placebo.

“This research indicates the clinical significance of the prevalence estimator, in contrast to the conventional methodology which only considers the proportion of patients having at least one improvement event throughout the follow-up, to evaluate a treatment-induced improvement over the long term by assessing both the incidence and duration of the improvement,” the scientists wrote.

The distinction between the groups was even clearer after seven years of follow-up: 15.7% in the high-dose group, 10.4% in the low-dose, and 6.3% in the placebo group.

“The prevalence estimator was found to be more powerful at identifying a treatment impact than an improvement in EDSS alone,” the researchers concluded.