Professor Malcolm MacLeod (BSc(Hons) MBChB PhD FRCP Ed)
Professor of Neurology and Translational Neuroscience
- Centre for Clinical Brain Sciences
- Edinburgh CAMARADES group
- NHS Forth Valley
Contact details
- Email: Malcolm.macleod@ed.ac.uk
Responsibilities & affiliations
- Member, UK Home Office Animals in Science Committee
- Commissioner, Commission for Human Medicines, Medicines and Healthcare Products Regulatory Agency (MHRA)
Research summary
Every week around 3500 new pieces of research involving animals are published. It is almost impossible for anyone to stay up to date with current knowledge. We have also shown that much of that work is at substantial risk of bias - and the effects observed in animals may be substantially overstated as a consequence.
In our research we are developing tools to provide unbiased summaries of what is already known, including tools to assess whether effects in animals may be overstated. We then use this information to help guide better design of clinical trials testing treatments in humans.
Examples of trials we have helped design using this approach include EuroHYP-1 - a trial of brain cooling in stroke - and MS-SMART, a trial in secondary progressive multiple sclerosis.
Research aims and areas of interest
My group has led the development and application of systematic review and meta-analysis to the analysis of data from animal studies modelling neurological diseases such as stroke. This work allows an overview of how effective the drug is in animals; identification of the limits to efficacy in animals which might be relevant to human clinical trials; and an assessment of the risk that the findings of animal studies are biased because of poor experimental design.
Now we are using this information to provide guidance to those using, funding, publishing and measuring the contribution of research involving animals. With others we are seeking to develop ways of providing real-time summaries of the current state of knowledge to guide future research and to help with research resource allocation decisions. We are also developing techniques of meta-moderation and mediation analysis to better understand pathophysiological pathways in animal models of human diseases such as multiple sclerosis.
I am involved in clinical trials in stroke including EuroHYP-1, a 1500-patient trial of brain cooling for acute ischaemic stroke; FOCUS, a trial of antidepressants following stroke; and phase 1 studies testing the effectiveness of local brain cooling in reducing brain temperature.
Research group members
- Dr Emily Sena, Senior Post Doc and Deputy Group Leader
- Dr Gillian Currie, Post-doc
- Dr Jing Liao, Programmer
- Zsanett Bahor, PhD student
- Alexandra Bannach-Brown, Joint Aarhus-Edinburgh MSc/PhD student
Collaborators
- Prof David Howells, Florey Neurosciences Institute, Melbourne, Australia
- Prof Andrew Rice, Imperial College, London
- Prof Uli Dirnagl, Charite, Berlin
- Prof Greg Wegener, Aarhus University, Denmark
Sources of funding
- European Commission Seventh Framework Programme (FP7)
- NC3Rs (National Centre for the Replacement, Refinement & Reduction of Animals in Research)
Research activities
-
Identifying stroke therapeutics from preclinical models: A protocol for a novel application of network meta-analysis
In:
F1000Research, vol. 8, pp. 11
DOI: https://doi.org/10.12688/f1000research.15869.1
Contribution to journal › Article (Published) -
Machine learning algorithms for systematic review: reducing workload in a preclinical review of animal studies and reducing human screening error
In:
Systematic Reviews, vol. 8, no. 1
DOI: https://doi.org/10.1186/s13643-019-0942-7
Contribution to journal › Article (E-pub ahead of print) -
Protocol for a systematic review of guidelines for rigour in the design, conduct and analysis of biomedical experiments involving laboratory animals
In:
BMJ Open Science, vol. 2, no. 1, pp. e000004
DOI: https://doi.org/10.1136/bmjos-2018-000004
Contribution to journal › Article (E-pub ahead of print) -
PRECIOUS : PREvention of Complications to Improve OUtcome in elderly patients with acute Stroke. Rationale and design of a randomised, open, phase III, clinical trial with blinded outcome assessment
(8 pages)
In:
European Stroke Journal, vol. 3, no. 3, pp. 291-298
DOI: https://doi.org/10.1177/2396987318772687
Contribution to journal › Article (Published) -
The reproducibility opportunity
In:
Nature Human Behaviour
DOI: https://doi.org/10.1038/s41562-018-0398-0
Contribution to journal › Comment/debate (Published)