New publication: How we selected drugs for the MND-SMART clinical trial

Picture of the publication's first page on the BMJ Open Journal website

Feb 2023: We have published the detailed strategy for selection of the first two drugs in the MND-SMART clinical trial.

To select the first drugs for the MND-SMART clinical trial, we have used a systematic, evidence-based approach.

Charis Wong, a final year PhD student working with the CAMARADES group at the Centre for Clinical Brain Sciences, University of Edinburgh, has undertaken an in-depth analysis, the results of which have recently been published in the journal, BMJ Open.

Charis shared with us a summary of her recent publication.

Our methods of selecting the first two drugs (memantine and trazodone) in MND-SMART have recently been published. To guide drug selection, we worked with the CAMARADES group who are leaders in evidence synthesis.

Using a process call systematic review, we gathered, assess, and summaries published studies to guide decisions on drug selection by our expert panel.

We reviewed clinical studies in MND and other neurodegenerative diseases. We looked at studies in other neurodegenerative diseases as brain and nerve cells may be affected in a similar way in these disease as in MND. We also reviewed published MND preclinical (animal and cell) studies.

Our research retrieve nearly 30,000 clinical publications. We identified 595 interventions, of which 66 drugs were studied in at least one publication in MND or in two other diseases. Our large team of reviewers gathered data from publications for these drugs. Using a scoring system based on how effective and safe these drugs were, and how well the studies were conducted, we calculated scores and ranked each drug.

The expert panel used data from both clinical and preclinical reviews to inform discussions on shortlisting and selection of drugs for MND-SMART. They also considered new evidence such as from papers published after the reviews were started. By using this approach, we were able to provide a comprehensive, unbiased summary of published studies to guide expert panel decisions.

To help select future drugs, we are making this process more efficient by using artificial intelligence and automation. This will help us to keep u with the pace of studies being published. We are also expanding our approach to include different types of data such as stem cell drug screening data and data from drug and trial databases.

MND-SMART is a Euan MacDonald Centre clinical trial and is the UKs largest multi-arm, multi-stage clinical trial for MND.

Charis's PhD is supervised by Professor Malcolm Macleod (CAMARADES group) and Professor Siddharthan Chandran (Director, Euan MacDonald Centre).


Further reading and related links

You can read the published paper in full here on the BMJ Open website (open access)

Charis Wong's profile on the Anne Rowling Clinic webpage

CAMARADES University of Edinburgh webpages

Previous news article on systematic review in MND trials

Research case studies - stem-cells and MND 'in a dish'

MND-SMART website

Professor Malcolm Macleod

Professor Siddharthan Chandran

This article was published on: Monday, February 06, 2023