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Ther Adv Neurol Disord. 2019 May 13;12:1756286419847095. doi: 10.1177/1756286419847095. eCollection 2019.

Clinical trials in multiple sclerosis: potential future trial designs.

Author information

1
Department of Neurology and Neurotherapeutics, The University of Texas Southwestern Medical Center, Dallas, TX.
2
Division of Biostatistics, Washington University School of Medicine, St. Louis, MO.
3
Department of Neurology, UKD and Center for Neurology and Neuropsychiatry, LVR Klinikum, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
4
Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Germany.
5
Department of Neurology, University of Regensburg, Germany.
6
Department of Neurology, University of Michigan, Ann Arbor, MI.
7
Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL.
8
Neurology Section, VA North Texas Health Care System, Medical Service, 500 South Lancaster Rd., Dallas, TX 75216, USA Department of Neurology and Neurotherapeutics, The University of Texas Southwestern Medical Center, Dallas, TX Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Germany.

Abstract

Clinical trials of new treatments in multiple sclerosis (MS) currently require large sample sizes and long durations in order to yield reliable results. The differential responses of an already heterogeneous population of MS patients to individual disease-modifying therapies (DMTs) will further complicate future trials. MS trials with smaller samples and faster outcomes are conceivable through the substitution of current clinical and MRI outcomes with objectively measureable genomic and proteomic biomarkers. Currently, biomarkers that could be utilized for diagnosis and monitoring of MS disease activity are in the early validation phase. The power of single biomarkers or multiple correlated biomarkers to predict prognosis and response to treatment could initially be compared with currently accepted methods. These prospectively validated disease biomarkers could then be used to subcategorize the spectrum of MS patients into a finite number of endophenotypes with demonstrable different molecular pathogeneses and DMT response profiles. Newly developed DMT could potentially be assessed within specific endophenotypes and compared with pharmacogenomically relevant active comparator DMT. This approach may increase the efficiency of MS trials through homogenization of patient population and minimization of nonresponders in study groups, providing the potential for the development of targeted therapies.

KEYWORDS:

Clinical trial; Disease Modifying therapy; Endophenotypes; Multiple Sclerosis; Pharmacology; Trial design

Conflict of interest statement

Conflict of interest statement: The authors declare that there is no conflict of interest.

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