a selection of scientific papers strewn randomly

Scientific publications

Scientific publications

A list of our scientific publications related to MND-SMART. The publications describe our methodology and results in detail. All these published articles have been "peer-reviewed", which means that they have been scrutinised by two or three independent experts.

2023

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)

  • In this short correspondence the MND-SMART trial team, and the people living with MND who are co-producing the trial, consider the pros and cons of including a placebo group in a trial like MND-SMART. Including a placebo group means that some people will be randomly assigned to receive a dummy pill, and as such will not be taking the drugs being tested.

    Of course, the obvious down-side of using a placebo group is that there is no opportunity for these individuals to receive any beneficial effects of the drugs being tested. Also, if all participants were taking active drug, it would be quicker to gather enough data to draw conclusions about its effectiveness.

    However, there are strong counter-arguments in favour of including a placebo group. Using a placebo group of participants drawn from the same population at the same time as those taking active drug is the best way to avoid uncertainty about the robustness of any results, which may slow down regulatory approval and indeed mean that a further trial is needed. In addition, people randomly assigned to a placebo group have no risk of adverse side effects.

    In conclusion, the authors recommend that placebo arms should continue in MND-SMART and other similar trials, but that it is important to continue to research how to minimise the number of trial participants taking a placebo without compromising the results.

 

Systematic, comprehensive, evidence-based approach to identify neuroprotective interventions for motor neuron disease: using systematic reviews to inform expert consensus
Wong C, Gregory JM, Liao J, et al. BMJ Open 2023;13:e064169.doi: 10.1136/bmjopen-2022-064169
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.

 
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
 

 

 

 

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