Improving the efficiency of clinical trials in multiple sclerosis-Reference-Cited by-同舟云学术

Improving the efficiency of clinical trials in multiple sclerosis

Published:2023-08 Issue:9 Volume:29 Page:1136-1148
ISSN:1352-4585
Container-title:Multiple Sclerosis Journal
language:en
Short-container-title:Mult Scler

Author:

Marrie Ruth Ann¹^ORCID,Sormani Maria Pia²^ORCID,Apap Mangion Sean³,Bovis Francesca⁴,Cheung Winson Y⁵,Cutter Gary R⁶^ORCID,Feys Peter⁷,Hill Michael D⁸,Koch Marcus Werner⁹^ORCID,McCreary Morgan¹⁰^ORCID,Mowry Ellen M¹¹,Park Jay JH¹²,Piehl Fredrik¹³^ORCID,Salter Amber¹⁰^ORCID,Chataway Jeremy¹⁴

Affiliation:

1. Departments of Internal Medicine and Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada

2. Department of Health Sciences, University of Genoa, Genoa, Italy/IRCCS Ospedale Policlinico San Martino, Genoa, Italy

3. Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK

4. Department of Health Sciences, University of Genoa, Genoa, Italy

5. Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

6. Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA

7. REVAL Rehabilitation Research Center, REVAL, Faculty of Rehabilitation Sciences, Hasselt University, Hasselt, Belgium/Universitair MS Centrum, UMSC, Hasselt, Belgium

8. Departments of Clinical Neurosciences, Community Health Sciences, Medicine, and Radiology, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

9. Departments of Clinical Neurosciences, Community Health Sciences, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

10. Department of Neurology, Section on Statistical Planning and Analysis, UT Southwestern Medical Center, Dallas, TX, USA

11. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

12. Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada

13. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

14. Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK/National Institute for Health Research, University College London Hospitals, Biomedical Research Centre, London, UK/Medical Research Council Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK

Abstract

Background:Phase 3 clinical trials for disease-modifying therapies in relapsing-remitting multiple sclerosis (RRMS) have utilized a limited number of conventional designs with a high degree of success. However, these designs limit the types of questions that can be addressed, and the time and cost required. Moreover, trials involving people with progressive multiple sclerosis (MS) have been less successful.Objective:The objective of this paper is to discuss complex innovative trial designs, intermediate and composite outcomes and to improve the efficiency of trial design in MS and broaden questions that can be addressed, particularly as applied to progressive MS.Methods:We held an international workshop with experts in clinical trial design.Results:Recommendations include increasing the use of complex innovative designs, developing biomarkers to enrich progressive MS trial populations, prioritize intermediate outcomes for further development that target therapeutic mechanisms of action other than peripherally mediated inflammation, investigate acceptability to people with MS of data linkage for studying long-term outcomes of clinical trials, use Bayesian designs to potentially reduce sample sizes required for pediatric trials, and provide sustained funding for platform trials and registries that can support pragmatic trials.Conclusion:Novel trial designs and further development of intermediate outcomes may improve clinical trial efficiency in MS and address novel therapeutic questions.

Funder

National Multiple Sclerosis Society

European Committee for Treatment and Research in Multiple Sclerosis

Publisher

SAGE Publications

Subject

Neurology (clinical),Neurology

Link

http://journals.sagepub.com/doi/pdf/10.1177/13524585231189671

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