The SMART – or Systematic Multi-arm Adaptive Randomised Trial - model tests several drugs at once often against a shared placebo, so we find out sooner which ones help people living with neurodegenerative conditions.
At the UK DRI, we run MND-SMART and AD-SMART, pioneering a model to apply to further neurodegenerative conditions.
Traditional trials test a single drug, take years to report, then are taken down. The next drug starts again from scratch. For people living with conditions like Alzheimer’s and motor neuron disease, that pace is not good enough.
It’s like building a football stadium for a single match, then tearing it down. A SMART trial keeps the stadium standing, so we can play match after match.
For too long, Alzheimer’s research has moved at the pace of one drug, one trial, one answer, sometimes taking a decade or more before we know if we’ve found something that works.
How SMART works
- Test several drugs at once. Each group of participants takes a different drug, and often all are compared with one shared placebo group. More people receive an active treatment than in a traditional trial.
- Find out what really works. People are put into groups by chance, so the groups are as similar as possible at the start. That means any differences we see in people’s health can be put down to the treatment itself. Neither participants nor researchers know who is taking what until the end of the treatment period.
- Check results along the way. At planned points, the evidence collected so far is reviewed.
- Stop, keep or add. Drugs that aren’t helping are stopped quickly and new ones take their place. People who were taking a stopped drug may be able to rejoin the trial on a different arm, if eligible. Fewer people take ineffective drugs, and the trial keeps running.
SMART trials meet the same rigorous standards as any Phase III trial, with every decision made by pre-planned rules. If positive, the trial can move seamlessly into the next Phase.
SMART trials running now
MND-SMART · since 2020
The UK’s SMART trial for MND, run from the Euan MacDonald Centre at the University of Edinburgh.
MND-SMART launched in 2020 and tested its first three drugs in just over five years. Testing them one after the other would have taken at least 15 years.
A result that says a drug doesn’t work is still progress. People stop waiting on it, and the next treatment gets its chance sooner. This information can feed back into the discovery research to provide information on mechanisms and allowing new avenues to be explored or closed off.
MND-SMART is funded by Euan MacDonald Centre for MND Research, as well as research grants from the Motor Neurone Disease Association, MND Scotland, The Alan Davidson Foundation, My Name'5 Doddie Foundation, and Baillie Gifford.
Chief Investigators
MND-SMART participants and researchers at an event in 2024
have taken part
across all four UK nations
to deliver the first answers, not 15
We already know this model works. The SMART approach, used by MND-SMART, has shown that testing multiple drugs at once, in one smart trial design, can speed up the testing of new treatments for neurodegenerative conditions.
Director & CEO
Find out more about MND-SMART:
AD-SMART · launched October 2026
The first trial of its kind for Alzheimer’s. It starts by testing two existing medicines – atomoxetine, used for ADHD, and metformin, used for type 2 diabetes – to see if they can ease symptoms and help people live well for longer.
AD-SMART aims to recruit 1,200 people, with more than 30 NHS sites planned. First results are expected in 2030.
AD-SMART is led by the UK DRI and Alzheimer’s Research UK in partnership with Health Data Research UK, with support from the MRC and NIHR.
Chief Investigator
Find out more about AD-SMART:
A model built for many conditions
Neurodegenerative conditions share causes, and they share the same problem: too few treatments, tested too slowly. The SMART model works for any condition where several promising treatments are waiting to be tested. The UK DRI is working with partners to bring it to more of the conditions we study.
What carries across from one SMART trial to the next:
- the trial design and statistics, already proven, published, and approved by the regulators
- NHS sites, staff and systems that stay open between drugs
- ways of choosing drugs with people affected, clinicians and industry
- lessons from the lab, feeding new treatments in