Clinical trials in multiple sclerosis: potential future trial designs

Navid Manouchehri, Yinan Zhang, Amber Salter, Rehana Z. Hussain, Hans Peter Hartung, Bernhard Hemmer, Ralf Linker, Benjamin M. Segal, Gary Cutter, Olaf Stuve

Research output: Contribution to journalReview article

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.

Original languageEnglish (US)
JournalTherapeutic Advances in Neurological Disorders
Volume12
DOIs
StatePublished - May 1 2019

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Multiple Sclerosis
Clinical Trials
Biomarkers
Endophenotypes
Therapeutics
Sample Size
Proteomics
Population

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology

Cite this

Clinical trials in multiple sclerosis : potential future trial designs. / Manouchehri, Navid; Zhang, Yinan; Salter, Amber; Hussain, Rehana Z.; Hartung, Hans Peter; Hemmer, Bernhard; Linker, Ralf; Segal, Benjamin M.; Cutter, Gary; Stuve, Olaf.

In: Therapeutic Advances in Neurological Disorders, Vol. 12, 01.05.2019.

Research output: Contribution to journalReview article

Manouchehri, N, Zhang, Y, Salter, A, Hussain, RZ, Hartung, HP, Hemmer, B, Linker, R, Segal, BM, Cutter, G & Stuve, O 2019, 'Clinical trials in multiple sclerosis: potential future trial designs', Therapeutic Advances in Neurological Disorders, vol. 12. https://doi.org/10.1177/1756286419847095
Manouchehri, Navid ; Zhang, Yinan ; Salter, Amber ; Hussain, Rehana Z. ; Hartung, Hans Peter ; Hemmer, Bernhard ; Linker, Ralf ; Segal, Benjamin M. ; Cutter, Gary ; Stuve, Olaf. / Clinical trials in multiple sclerosis : potential future trial designs. In: Therapeutic Advances in Neurological Disorders. 2019 ; Vol. 12.
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