Validity of the Symbol Digit Modalities Test as a cognition performance outcome measure for multiple sclerosis

Ralph Hb Benedict, John DeLuca, Glenn Phillips, Nicholas LaRocca, Lynn D Hudson, Richard Rudick, Multiple Sclerosis Outcome Assessments Consortium, Ralph Hb Benedict, John DeLuca, Glenn Phillips, Nicholas LaRocca, Lynn D Hudson, Richard Rudick, Multiple Sclerosis Outcome Assessments Consortium

Abstract

Cognitive and motor performance measures are commonly employed in multiple sclerosis (MS) research, particularly when the purpose is to determine the efficacy of treatment. The increasing focus of new therapies on slowing progression or reversing neurological disability makes the utilization of sensitive, reproducible, and valid measures essential. Processing speed is a basic elemental cognitive function that likely influences downstream processes such as memory. The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) includes representatives from advocacy organizations, Food and Drug Administration (FDA), European Medicines Agency (EMA), National Institute of Neurological Disorders and Stroke (NINDS), academic institutions, and industry partners along with persons living with MS. Among the MSOAC goals is acceptance and qualification by regulators of performance outcomes that are highly reliable and valid, practical, cost-effective, and meaningful to persons with MS. A critical step for these neuroperformance metrics is elucidation of clinically relevant benchmarks, well-defined degrees of disability, and gradients of change that are deemed clinically meaningful. This topical review provides an overview of research on one particular cognitive measure, the Symbol Digit Modalities Test (SDMT), recognized as being particularly sensitive to slowed processing of information that is commonly seen in MS. The research in MS clearly supports the reliability and validity of this test and recently has supported a responder definition of SDMT change approximating 4 points or 10% in magnitude.

Keywords: Multiple sclerosis; Symbol Digit Modalities Test; cognition; performance outcome; processing speed; psychometric validity.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Benedict receives research support from Accorda, Novartis, Genzyme, Biogen, and Mallinckrodt Pharmaceuticals; is on the speakers’ bureau for EMD Serono (designing CME courses); consults for Biogen, Genentech, Genzyme, Novartis, Abbvie, Roche and Sanofi; and receives royalties from Psychological Assessment Resources. Dr DeLuca receives grant funding from Biogen and EMD Serono, serves on an Advisory board for Biogen, and is on the speakers’ bureau for EMD Serono.

Figures

Figure 1.
Figure 1.
(a) The Symbol Digit Modalities Test as originally developed by Whipple and Pyle in the early 20th century. This is the earliest description of a symbol/number coding task we are able to locate, and neither source refers to a prior version of the task. (b) A scored version of the Digit Symbol Substitution Test as developed for the US Army in the early 1920s, subsequently adapted by the Wechsler intelligence scales. (c) A faux version of the Symbol Digit Modalities Test (SDMT) as presented in an earlier publication on the Brief International Cognitive Assessment for MS (BICAMS).
Figure 2.
Figure 2.
Mean effect sizes and ranges for each of the more commonly used neuropsychological tests in consensus standard batteries. Figure shows the mean effect size as calculated by the Cohen d method where d is the difference between group means divided by the average SD. All d values reflect MS and healthy control group comparisons. SDMT has a larger mean effect size as compared to others depicted.

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