Evidence map›Paper›PMID 36647114›Full record

ArticleTrials2023

Statistical analysis plan for the motor neuron disease systematic multi-arm adaptive randomised trial (MND-SMART).

Richard A Parker, Christopher J Weir, Tra My Pham, Ian R White, Nigel Stallard, Mahesh K B Parmar, Robert J Swingler, Rachel S Dakin, Suvankar Pal, Siddharthan Chandran

Registry-linked trialAbstract readClinical Trial Protocol
PubMed Full text at PMC Publisher
In one paragraph

Article in Trials, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04302870 (Motor Neurone Disease - Systematic Multi-Arm Adaptive Randomised Trial), which is not on this map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04302870 phase2 / phase3recruitingnot on this map

Motor Neurone Disease - Systematic Multi-Arm Adaptive Randomised Trial

TypeinterventionalSponsorUniversity of EdinburghRan2020 to 2030Enrolled1,150ConditionsMotor Neuron Disease, Amyotrophic Lateral SclerosisArmsMemantine Hydrochloride Oral Solution, Trazodone Hydrochloride oral solution, Placebo oral solution, Amantadine Hydrochloride Oral Solution, Tacrolimus 1Mg Cap
3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Richard A ParkerEdinburgh Clinical Trials Unit, Usher Institute, University of Edinburgh, Edinburgh, UK. Richard.Parker@ed.ac.uk.ORCID http://orcid.org/0000-0002-2658-5022
Christopher J WeirEdinburgh Clinical Trials Unit, Usher Institute, University of Edinburgh, Edinburgh, UK.
Tra My PhamMedical Research Council Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK.
Ian R WhiteMedical Research Council Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK.
Nigel StallardStatistics and Epidemiology, Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry, UK.
Mahesh K B ParmarMedical Research Council Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK.
Robert J SwinglerEuan Macdonald Centre for Motor Neuron Disease Research, University of Edinburgh, Edinburgh, EH16 4SB, UK.
Rachel S DakinEuan Macdonald Centre for Motor Neuron Disease Research, University of Edinburgh, Edinburgh, EH16 4SB, UK.
Suvankar PalEuan Macdonald Centre for Motor Neuron Disease Research, University of Edinburgh, Edinburgh, EH16 4SB, UK.
Siddharthan ChandranEuan Macdonald Centre for Motor Neuron Disease Research, University of Edinburgh, Edinburgh, EH16 4SB, UK.

Funding

Medical Research Council MC_EX_MR/N50192X/1Medical Research Council MC_UU_00004/07MRF_ MRF-024-0001-RG-PARM-C0860
6 · The paper itself

Abstract

backgroundMND-SMART is a platform, multi-arm, multi-stage, multi-centre, randomised controlled trial recruiting people with motor neuron disease. Initially, the treatments memantine and trazodone will each be compared against placebo, but other investigational treatments will be introduced into the trial later. The co-primary outcomes are the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALS-FRS-R) functional outcome, which is assessed longitudinally, and overall survival.

methodsInitially in MND-SMART, participants are randomised 1:1:1 via a minimisation algorithm to receive placebo or one of the two investigational treatments with up to 531 to be randomised in total. The comparisons between each research arm and placebo will be conducted in four stages, with the opportunity to cease further randomisations to poorly performing research arms at the end of stages 1 or 2. The final ALS-FRS-R analysis will be at the end of stage 3 and final survival analysis at the end of stage 4. The estimands for the co-primary outcomes are described in detail. The primary analysis of ALS-FRS-R at the end of stages 1 to 3 will involve fitting a normal linear mixed model to the data to calculate a mean difference in rate of ALS-FRS-R change between each research treatment and placebo. The pairwise type 1 error rate will be controlled, because each treatment comparison will generate its own distinct and separate interpretation. This publication is based on a formal statistical analysis plan document that was finalised and signed on 18 May 2022. DISCUSSION: In developing the statistical analysis plan, we had to carefully consider several issues such as multiple testing, estimand specification, interim analyses, and statistical analysis of the repeated measurements of ALS-FRS-R. This analysis plan attempts to balance multiple factors, including minimisation of bias, maximising power and precision, and deriving clinically interpretable summaries of treatment effects.

trial registrationEudraCT Number, 2019-000099-41. Registered 2 October 2019, https://www.clinicaltrialsregister.eu/ctr-search/search?query=mnd-smart ClinicalTrials.gov, NCT04302870 . Registered 10 March 2020.

Indexed as

Amyotrophic Lateral SclerosisMotor Neuron DiseaseAdaptive Clinical Trials as TopicHumansMulticenter Studies as TopicRandomized Controlled Trials as TopicTherapies, InvestigationalTranscranial Magnetic StimulationTreatment OutcomeMAMS trialMotor neuron diseaseMulti-armPlatform trialStatistical analysis plan

Identifiers

PMID36647114
PMCPMC9843918

What OpenQuestion holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.