National MS Society-Sponsored Group Creates Tool Set to Measure Outcomes in MS Clinical Trials

Four newly published articles, the focused work of a group of researchers, evaluate the validity of four outcome measures commonly used in clinical trials of multiple sclerosis (MS) to set standards for such measures, the National MS Society recently reported.

The effort by the Society-sponsored MS Outcome Assessments Consortium (MSOAC) aims to increase the speed of clinical trials by identifying tools that best mirror changes in disease aspects that include walking, vision, cognition, and hand movements.

The four articles, published in the Multiple Sclerosis Journal, are available to the public:

• Validity of the Symbol Digit Modalities Test as a cognition performance outcome measure for multiple sclerosis
• Validity of low-contrast letter acuity as a visual performance outcome measure for multiple sclerosis
• Validity of the timed 25-foot walk as an ambulatory performance outcome measure for multiple sclerosis
• The Nine-Hole Peg Test as a manual dexterity performance measure for multiple sclerosis

While the choice of an outcome measure may mean little to the average patient, not all measures are equal. Some measures of cognition, for instance, may capture the specific deterioration in MS better than others. Only through a thorough assessment of analytic tools can researchers be certain that they measure what they intend to measure in a valid way.

The assessment was based on extensive reviews of published literature and clinical trial data.

The four tools assessed by the Consortium were the Symbol Digit Modalities Test, measuring information processing speed as an aspect of cognition; the 9-hole peg test for measuring manual dexterity performance — or the ability to perform hand and finger movements; the Timed-25-Foot Walk as a measure of ambulation; and the Sloan low-contrast letter acuity test for measuring vision.

The publications concluded that all four tools — widely used in clinical trials — are reliable and valid for use with MS patients with MS. But the researchers underscored that these four measures are not necessarily enough to explain every aspect of a disability, and have their constraints.

In an accompanying editorial, three researchers from the VU University Medical Center in the Netherlands and University College London in the U.K. also pointed out that although the measures are good at providing statistical evidence of change, how well they reflect real changes for patients also needs to be a research focus.

“We are able to tell the ‘statistical tale.’ But there is more to pursue: in this day and age, where personalized medicine and patient-tailored care are central concepts, we need to identify changes on these outcome measures that have a clinical impact on our patients’ lives,” the three wrote.

For instance, they asked how a two-point improvement on the cognitive test would translate into effects seen in a patient’s daily life.

MSOAC is now preparing an application for receive regulatory approval, in both the U.S. and Europe, for a tool set for use in MS trials. Once approval is in place, the tool set — along with instructions on its use — will be freely available to all researchers.

MSOAC is composed of researchers from academic institutions, pharmaceutical companies, the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the National Institutes of Health (NIH).

The initiative was launched in 2011, after a National MS Society-supported task force decided that a collaboration with the Critical Path Institute was necessary to address the need for better measures of MS-related disability in clinical trials.

The Institute is a non-profit partner to the FDA, and works to speed up the pace and reduce costs of medical product development by developing new standards for evaluation.

MSOAC earlier developed new MS data standards, named CDISC standards. Such standardization of data allows researchers to harmonize data from different studies. In the future, the FDA will require clinical trials to use standardized data.

Another effort by the Consortium led to the release of a subset of the data, containing nearly 2,500 patient records (with patients’ identity removed) from the placebo groups of nine MS clinical trials. This data will be accessible by qualified investigators and used to answer additional research questions not addressed in trials.