Clinical trials in amyotrophic lateral sclerosis: a systematic review and perspective-Reference-Cited by-同舟云学术

Clinical trials in amyotrophic lateral sclerosis: a systematic review and perspective

Published:2021-10-01 Issue:4 Volume:3 Page:
ISSN:2632-1297
Container-title:Brain Communications
language:en
Short-container-title:

Author:

Wong Charis¹²³^ORCID,Stavrou Maria¹²³⁴,Elliott Elizabeth¹²³⁴,Gregory Jenna M¹³⁴^ORCID,Leigh Nigel⁵,Pinto Ashwin A⁶,Williams Timothy L⁷,Chataway Jeremy⁸⁹¹⁰^ORCID,Swingler Robert³,Parmar Mahesh K B¹⁰,Stallard Nigel¹¹^ORCID,Weir Christopher J¹²,Parker Richard A¹²,Chaouch Amina¹³,Hamdalla Hisham¹³,Ealing John¹³,Gorrie George¹⁴,Morrison Ian¹⁵^ORCID,Duncan Callum¹⁶,Connelly Peter¹⁷,Carod-Artal Francisco Javier¹⁸,Davenport Richard²¹⁹,Reitboeck Pablo Garcia²⁰,Radunovic Aleksandar²¹,Srinivasan Venkataramanan²²,Preston Jenny²³,Mehta Arpan R¹²³⁴^ORCID,Leighton Danielle¹³,Glasmacher Stella¹²³,Beswick Emily¹²³,Williamson Jill¹²³,Stenson Amy¹²³,Weaver Christine¹²³,Newton Judith¹²³,Lyle Dawn¹²³,Dakin Rachel¹²³,Macleod Malcolm¹^ORCID,Pal Suvankar¹²³,Chandran Siddharthan¹²³⁴

Affiliation:

1. Centre for Clinical Brain Sciences, Chancellor's Building, 49 Little France Crescent, The University of Edinburgh, Edinburgh, EH16 4SB, UK

2. Anne Rowling Regenerative Neurology Clinic, Chancellor's Building, 49 Little France Crescent, The University of Edinburgh, Edinburgh, EH16 4SB, UK

3. Euan MacDonald Centre for MND Research, University of Edinburgh, FU303F, Chancellor’s Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK

4. UK Dementia Research Institute, Chancellor’s Building, The University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK

5. Department of Neuroscience, Brighton and Sussex Medical School, University of Sussex, Brighton, BN1 9PX, UK

6. Neurology Department, Wessex Neurosciences Centre, Southampton General Hospital, Southampton, SO16 6YD, UK

7. Department of Neurology, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, UK

8. Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London WC1B 5EH, UK

9. National Institute for Health Research, University College London Hospitals, Biomedical Research Centre, London, W1T 7DN, UK

10. MRC CTU at UCL, Institute of Clinical Trials and Methodology, University College London, London, WC1V 6LJ, UK

11. Statistics and Epidemiology, Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK

12. Edinburgh Clinical Trials Unit, Usher Institute, Level 2, NINE Edinburgh BioQuarter, 9 Little France Road, Edinburgh EH16 4UX, UK

13. Motor Neurone Disease Care Centre, Manchester Centre for Clinical Neurosciences, Salford, M6 8HD, UK

14. Department of Neurology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde, Glasgow, G51 4TF, UK

15. Department of Neurology, NHS Tayside, Dundee, DD2 1UB, UK

16. Department of Neurology, Aberdeen Royal Infirmary, Aberdeen, AB25 2ZN, UK

17. NHS Research Scotland Neuroprogressive Disorders and Dementia Network, Ninewells Hospital, Dundee, DD1 9SY, UK

18. Department of Neurology, NHS Highland, Inverness, IV2 3UJ, UK

19. Department of Clinical Neurosciences, NHS Lothian, Edinburgh, EH16 4SA, UK

20. Atkinson Morley Regional Neurosciences Centre, St. George's University Hospitals NHS Foundation Trust, London SW17 0QT, UK

21. Barts MND Centre, Barts Health NHS Trust, London, E1 1FR, UK

22. Department of Neurology, Queen Elizabeth Hospital Birmingham, Birmingham, B15 2GW, UK

23. Department of Neurology, NHS Ayrshire & Arran, KA12 8SS, UK

Abstract

Abstract Amyotrophic lateral sclerosis is a progressive and devastating neurodegenerative disease. Despite decades of clinical trials, effective disease-modifying drugs remain scarce. To understand the challenges of trial design and delivery, we performed a systematic review of Phase II, Phase II/III and Phase III amyotrophic lateral sclerosis clinical drug trials on trial registries and PubMed between 2008 and 2019. We identified 125 trials, investigating 76 drugs and recruiting more than 15 000 people with amyotrophic lateral sclerosis. About 90% of trials used traditional fixed designs. The limitations in understanding of disease biology, outcome measures, resources and barriers to trial participation in a rapidly progressive, disabling and heterogenous disease hindered timely and definitive evaluation of drugs in two-arm trials. Innovative trial designs, especially adaptive platform trials may offer significant efficiency gains to this end. We propose a flexible and scalable multi-arm, multi-stage trial platform where opportunities to participate in a clinical trial can become the default for people with amyotrophic lateral sclerosis.

Funder

MND Scotland, My Name’5 Doddie Foundation

UK Dementia Research Institute

UK DRI Ltd

UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK

Medical Research Council (MRC) and the Motor Neurone Disease Association

Publisher

Oxford University Press (OUP)

Subject

General Earth and Planetary Sciences,General Environmental Science

Link

http://academic.oup.com/braincomms/advance-article-pdf/doi/10.1093/braincomms/fcab242/40830801/fcab242.pdf