2024
Safety and efficacy of memantine and trazodone versus placebo for motor neuron disease (MND SMART): stage two interim analysis from the first cycle of a phase 3, multiarm, multistage, randomised, adaptive platform trial.
Pal S, Chataway J, Swingler R, Macleod MR, Carragher NO, Hardingham G, Selvaraj BT, Smith C, Wong C, Newton J, Lyle D, Stenson A, Dakin RS, Ihenacho A, Colville S, Mehta AR, Stallard N, Carpenter JR, Parker RA, Keerie C, Weir CJ, Virgo B, Morris S, Waters N, Gray B, MacDonald D, MacDonald E, Parmar MKB, Chandran S. The Lancet Neurology (2024). https://doi.org/10.1016/S1474-4422(24)00326-0
- Results of the first two drugs definitvely tested in the MND-SMART trial. Read more in the news article: First results published from innovative platform trial, MND-SMART, aiming to speed up delivery of treatments for motor neuron disease | MND-SMART
2023
Factors impacting trial participation in people with motor neuron disease
Beswick E, Johnson M, Newton J, Dakin R, Stenson A, Abrahams A, Carson A, Chandran S, Pal S. J Neurol (2023). doi:10.1007/s00415-023-12010-8
The role of placebo control in clinical trials for neurodegenerative diseases
Mehta AR, Carpenter JR, Nicholas JM, Chataway J, Virgo B, Parmar MKB, Chandran S, Pal S. Nat Med. 2023 Sep 14. doi: 10.1038/d41591-023-00080-0. (article not freely available; unformatted version available via Edinburgh Research Explorer)
- The MND-SMART trial team, and the people living with MND who are co-producing the trial, have considered the pros and cons of including a placebo group in a trial like MND-SMART. Read more in the news article: The role of placebo control in clinical trials for neurodegenerative diseases.
Systematic, comprehensive, evidence-based approach to identify neuroprotective interventions for motor neuron disease: using systematic reviews to inform expert consensus
- Detailed description of the systematic, structured and evidence-based approach used to select the first two drugs used in MND-SMART (trazodone and memantine). Read more in the news article: New publication: How we selected drugs for the MND-SMART clinical trial.
Statistical analysis plan for the motor neuron disease systematic multi-arm adaptive randomised trial (MND-SMART)
Parker RA, Weir CJ, Pham TM, White IR, Stallard N, Parmar MKB, Swingler RJ, Dakin RS, Pal S, Chandran S. Trials. 2023 Jan 16;24(1):29. doi: 10.1186/s13063-022-07007-z.
- Detailed description of the statistical analyses that will be applied to the trial data. The plan has been designed to minimise bias, and maximise the likelihood of deriving accurate results that give clinically meaningful information about the treatment effects of the drugs being tested.
2022
Motor Neuron Disease Systematic Multi-Arm Adaptive Randomised Trial (MND-SMART): a multi-arm, multi-stage, adaptive, platform, phase III randomised, double-blind, placebo-controlled trial of repurposed drugs in motor neuron disease
Wong C, Dakin RS, Williamson J, Newton J, Steven M, Colville S, Stavrou M, Gregory JM, Elliott E, Mehta AR, Chataway J, Swingler RJ, Parker RA, Weir CJ, Stallard N, Parmar MKB, Macleod MR, Pal S, Chandran S. BMJ Open. 2022 Jul 7;12(7):e064173. doi: 10.1136/bmjopen-2022-064173.
- Detailed description of the MND-SMART trial protocol. Read more in the news article: MND Study Protocol Published
Smarter adaptive platform clinical trials in neurology: a showcase for UK innovation
Arpan R. Mehta, Suvankar Pal, Jeremy Chataway, James R. Carpenter, Mahesh K. B. Parmar, Siddharthan Chandran. Brain. 2022 Aug;145(8):e64-65. doi: 10.1093/brain/awac169 (article not freely available; unformatted version available via Edinburgh Research Explorer)
- In this Letter to the Editor, the authors discuss how innovation in clinical trial design - learning from cancer trials - and novel laboratory techniques have opened up opportunities for innovation in trials for brain conditions, particularly through the ACORD collaboration [see 2021 article below]. MND-SMART is used as an example of a next-generation neurology trial.
2021
Trials for neurodegenerative diseases: time to innovate
Arpan R Mehta, Jeremy Chataway, Suvankar Pal, Mahesh K B Parmar, Siddharthan Chandran. Lancet Neurology. 2021 Dec;20(12):984. doi: 10.1016/S1474-4422(21)00388-4 (freely available via PubMedCentral)
- This short comment introduces the concept of complex clinical trial designs for neurodegenerative diseases, and suggests that there is much to be learned from advances in cancer trials. The article introduces ACORD (A Collaboration Of groups developing, Running and reporting platform trials in neurodegenerative Diseases), a UK-wide consortium hosted by the Medical Research Council Clinical Trials Unit at University College London, to share ideas and approaches.
Prospective observational cohort study of factors influencing trial participation in people with motor neuron disease (FIT-participation-MND): a protocol
Beswick E, Glasmacher SA, Dakin R, Newton J, Carson A, Abrahams S, Chandran S, Pal S. BMJ Open. 2021 Mar 23;11(3):e044996. doi: 10.1136/bmjopen-2020-044996.
- This paper describes the protocol for an MND-SMART substudy, which examined the factors that affect whether people join MND-SMART, and crucially, what affects whether they stay in the trial. Improved understanding of these factors may improve trial protocol design, optimise recruitment and retention. Read more in the news article: MND-SMART substudy 1