Symbol Digit Modalities Test: A valid clinical trial endpoint for measuring cognition in multiple sclerosis

Lauren Strober, John DeLuca, Ralph Hb Benedict, Adam Jacobs, Jeffrey A Cohen, Nancy Chiaravalloti, Lynn D Hudson, Richard A Rudick, Nicholas G LaRocca, Multiple Sclerosis Outcome Assessments Consortium (MSOAC), Lauren Strober, John DeLuca, Ralph Hb Benedict, Adam Jacobs, Jeffrey A Cohen, Nancy Chiaravalloti, Lynn D Hudson, Richard A Rudick, Nicholas G LaRocca, Multiple Sclerosis Outcome Assessments Consortium (MSOAC)

Abstract

Background: The need for more robust outcomes in multiple sclerosis (MS) clinical trials has been a main priority of the field for decades. Dissatisfaction with existing measures has led to several consensus meetings and initiatives over the past few decades in hopes of defining and gaining acceptance of measures that are valid, reliable, sensitive to change and progression, and most importantly, relevant to those living with MS. The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) was formed for this purpose.

Objective: The objective of this paper is to describe the results of the MSOAC plan to obtain qualification for a cognitive performance measure that meets these requirements.

Methods: Using data from 14 MS disease-modifying registration trials, we completed a comprehensive examination of the psychometric qualities of the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT) with the goal of compiling evidence to support the utilization of one of these measures in future clinical trials.

Results and conclusion: Consistent with the published literature, the SDMT proved superior to the PASAT. The SDMT should be considered the measure of choice for MS trials in assessing cognitive processing speed.

Keywords: Information processing speed; PASAT; performance measure; psychometric properties.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
(a) Distribution of Symbol Digit Modalities Test (SDMT) at baseline. The histogram of SDMT scores at baseline, representing 2583 PwMS, is presented. (b) Distribution of Paced Auditory Serial Addition Test (PASAT) scores at Baseline. The histogram of PASAT scores at baseline, representing 11,609 PwMS, is presented.
Figure 2.
Figure 2.
Kaplan–Meier graphs of disability worsening by various SDMT definitions. The percent of PwMS with worsening over time (in months) is shown for a 4-point change in SDMT, a 3-point change, a 20% change, a 15% change, and a 10% change. Each graph also shows the EDSS worsening over time in the PwMS. Kappa coefficients for agreement between SDMT and EDSS worsening were −0.02 (95% CI: −0.06 to −0.02) for 4-point SDMT worsening; –0.01 (95% CI: –0.05 to −0.03) for 3-point SDMT worsening; +0.03 (95% CI: –0.01 to +0.06) for 20% SDMT worsening; +0.01 (95% CI: –0.03 to +0.05) for 15% SDMT worsening; and −0.00 (95% CI: –0.04 to +0.04) for 10% SDMT worsening.

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Source: PubMed

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