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

Charis Wong; Maria Stavrou; Liz Elliott; Jenna Gregory; P. Nigel Leigh; Ashwin Pinto; Tim Williams; Jeremy Chataway; Robert Swingler; Mahesh K B Parmar; Nigel Stallard; Christopher J Weir; Richard A Parker; Amina Chaouch; Hisham Hamdalla; John Ealing; George Gorrie; I. Morrison; Callum Duncan; Peter Connelly; Francisco Javier Carod-Artal; Richard Davenport; Pablo Garcia Reitboeck; Aleksandar Radunovic; Venkataramanan Srinivasan; Jenny Preston; Arpan Mehta; Danielle Leighton; Stella Glasmacher; Emily Beswick; Jill Williamson; Amy Stenson; Christine Weaver; Judith Newton; Dawn Lyle; Rachel S. Dakin; Malcolm MacLeod; Suvankar Pal; Siddharthan Chandran

doi:10.1093/braincomms/fcab242

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

Charis Wong, Maria Stavrou, Liz Elliott, Jenna Gregory, P. Nigel Leigh, Ashwin Pinto, Tim Williams, Jeremy Chataway, Robert Swingler, Mahesh K B Parmar, Nigel Stallard, Christopher J Weir, Richard A Parker, Amina Chaouch, Hisham Hamdalla, John Ealing, George Gorrie, I. Morrison, Callum Duncan, Peter ConnellyFrancisco Javier Carod-Artal, Richard Davenport, Pablo Garcia Reitboeck, Aleksandar Radunovic, Venkataramanan Srinivasan, Jenny Preston, Arpan Mehta, Danielle Leighton, Stella Glasmacher, Emily Beswick, Jill Williamson, Amy Stenson, Christine Weaver, Judith Newton, Dawn Lyle, Rachel S. Dakin, Malcolm MacLeod, Suvankar Pal, Siddharthan Chandran^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Journal	Brain Communications
Volume	3
Issue number	4
Early online date	23 Oct 2021
DOIs	https://doi.org/10.1093/braincomms/fcab242 https://doi.org/10.1093/braincomms/fcab242
Publication status	E-pub ahead of print - 23 Oct 2021

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Cellular And Molecular Insights Into Neurodegeneration Mediated By The C9orf72 Gene Mutation
Mehta, A., Chandran, S. & Hardingham, G.
MRC
1/08/17 → 30/01/21
Project: Research

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Wong, C., Stavrou, M., Elliott, L., Gregory, J., Leigh, P. N., Pinto, A., Williams, T., Chataway, J., Swingler, R., Parmar, M. K. B., Stallard, N., Weir, C. J., Parker, R. A., Chaouch, A., Hamdalla, H., Ealing, J., Gorrie, G., Morrison, I., Duncan, C., ... Chandran, S. (2021). Clinical trials in amyotrophic lateral sclerosis: a systematic review and perspective. Brain Communications, 3(4). Advance online publication. https://doi.org/10.1093/braincomms/fcab242, https://doi.org/10.1093/braincomms/fcab242

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title = "Clinical trials in amyotrophic lateral sclerosis: a systematic review and perspective",

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.",

author = "Charis Wong and Maria Stavrou and Liz Elliott and Jenna Gregory and Leigh, {P. Nigel} and Ashwin Pinto and Tim Williams and Jeremy Chataway and Robert Swingler and Parmar, {Mahesh K B} and Nigel Stallard and Weir, {Christopher J} and Parker, {Richard A} and Amina Chaouch and Hisham Hamdalla and John Ealing and George Gorrie and I. Morrison and Callum Duncan and Peter Connelly and {Javier Carod-Artal}, Francisco and Richard Davenport and Reitboeck, {Pablo Garcia} and Aleksandar Radunovic and Venkataramanan Srinivasan and Jenny Preston and Arpan Mehta and Danielle Leighton and Stella Glasmacher and Emily Beswick and Jill Williamson and Amy Stenson and Christine Weaver and Judith Newton and Dawn Lyle and Dakin, {Rachel S.} and Malcolm MacLeod and Suvankar Pal and Siddharthan Chandran",

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doi = "10.1093/braincomms/fcab242",

language = "English",

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Wong, C, Stavrou, M, Elliott, L, Gregory, J, Leigh, PN, Pinto, A, Williams, T, Chataway, J, Swingler, R, Parmar, MKB, Stallard, N, Weir, CJ , Parker, RA, Chaouch, A, Hamdalla, H, Ealing, J, Gorrie, G, Morrison, I, Duncan, C, Connelly, P, Javier Carod-Artal, F, Davenport, R, Reitboeck, PG, Radunovic, A, Srinivasan, V, Preston, J, Mehta, A, Leighton, D, Glasmacher, S, Beswick, E, Williamson, J, Stenson, A, Weaver, C, Newton, J, Lyle, D, Dakin, RS, MacLeod, M , Pal, S & Chandran, S 2021, 'Clinical trials in amyotrophic lateral sclerosis: a systematic review and perspective', Brain Communications, vol. 3, no. 4. https://doi.org/10.1093/braincomms/fcab242, https://doi.org/10.1093/braincomms/fcab242

TY - JOUR

T1 - Clinical trials in amyotrophic lateral sclerosis

T2 - a systematic review and perspective

AU - Wong, Charis

AU - Stavrou, Maria

AU - Elliott, Liz

AU - Gregory, Jenna

AU - Leigh, P. Nigel

AU - Pinto, Ashwin

AU - Williams, Tim

AU - Chataway, Jeremy

AU - Swingler, Robert

AU - Parmar, Mahesh K B

AU - Stallard, Nigel

AU - Weir, Christopher J

AU - Parker, Richard A

AU - Chaouch, Amina

AU - Hamdalla, Hisham

AU - Ealing, John

AU - Gorrie, George

AU - Morrison, I.

AU - Duncan, Callum

AU - Connelly, Peter

AU - Javier Carod-Artal, Francisco

AU - Davenport, Richard

AU - Reitboeck, Pablo Garcia

AU - Radunovic, Aleksandar

AU - Srinivasan, Venkataramanan

AU - Preston, Jenny

AU - Mehta, Arpan

AU - Leighton, Danielle

AU - Glasmacher, Stella

AU - Beswick, Emily

AU - Williamson, Jill

AU - Stenson, Amy

AU - Weaver, Christine

AU - Newton, Judith

AU - Lyle, Dawn

AU - Dakin, Rachel S.

AU - MacLeod, Malcolm

AU - Pal, Suvankar

AU - Chandran, Siddharthan

PY - 2021/10/23

Y1 - 2021/10/23

N2 - 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.

AB - 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.

U2 - 10.1093/braincomms/fcab242

DO - 10.1093/braincomms/fcab242

M3 - Article

VL - 3

JO - Brain Communications

JF - Brain Communications

IS - 4

ER -

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

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Cellular And Molecular Insights Into Neurodegeneration Mediated By The C9orf72 Gene Mutation

Cite this