TY - JOUR
T1 - Clinical trials in amyotrophic lateral sclerosis
T2 - a systematic review and perspective
AU - Wong, Charis
AU - Stavrou, Maria
AU - Elliott, Elizabeth
AU - Gregory, Jenna M.
AU - Leigh, Nigel
AU - Pinto, Ashwin A.
AU - Williams, Timothy L.
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, Ian
AU - Duncan, Callum
AU - Connelly, Peter
AU - Carod-Artal, Francisco Javier
AU - Davenport, Richard
AU - Reitboeck, Pablo Garcia
AU - Radunovic, Aleksandar
AU - Srinivasan, Venkataramanan
AU - Preston, Jenny
AU - Mehta, Arpan R.
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
AU - Macleod, Malcolm
AU - Pal, Suvankar
AU - Chandran, Siddharthan
N1 - MND-SMART is funded by grants from MND Scotland, My Name’5 Doddie Foundation (DOD/14/15) and specific donations to the Euan MacDonald Centre. The Chandran lab is supported by the UK Dementia Research Institute, which receives its funding from UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK. A.R.M. is a Lady Edith Wolfson Clinical Fellow and is jointly funded by the Medical Research Council (MRC) and the Motor Neurone Disease Association (MR/R001162/1)
© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.
PY - 2021
Y1 - 2021
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.
KW - amyotrophic lateral sclerosis
KW - clinical trials
KW - systematic review
KW - methodology
KW - perspective
U2 - 10.1093/braincomms/fcab242
DO - 10.1093/braincomms/fcab242
M3 - Review article
C2 - 34901853
SN - 2632-1297
VL - 3
JO - Brain Communications
JF - Brain Communications
IS - 4
M1 - fcab242
ER -