What does an old children’s rhyme, a mouse, a clock and a tale of men including migrant workers with learning difficulties, have to do with my research into clinical trial design? The common factor is that “all” of these groups, grannies bouncing babies on their knees, people with learning difficulties, migrant workers, are, like many of us, people who may need medical treatment and can benefit from clinical trials. Sadly, many of them will be excluded.
Trials have been around a long time. Hickory dickory dock is reputed to date from 1744 shortly before James Lind, a ship’s surgeon on board HMS Salisbury, started his famous scurvy trial in 1747. He treated 12 sailors, two in each group with cider, sulphuric acid, usual gruel, sea water, vinegar and oranges and lemons – sailors barely able to walk, lying in their bunks with rotting bleeding gums. After six days, one sailor on oranges and lemons, was fit for duty. And as they say – the rest is history – fresh citrus fruit became part of the staple diet in the Royal Navy.
Enter the mouse – also on the ship. A pure beautiful white mouse is often the first for experimentation to determine if an intervention is safe before trials on humans. From Mice to Men, we progress through early phase trials that test safety and toxicity of a drug in a normal population to calculating safe doses and side effects in a diseased population. All of this work is essential and well regulated to protect patients, but we also need to know if a treatment will work on “all” patients who will ultimately receive the treatment in usual care.
My work has been looking at a tool to help people designing trials (trialists) consider the impact their design decisions have on the applicability of their results in clinical settings. This tool will help a trial team, right at the beginning of the design process to create trials that are more relevant to patients, health professionals and policy makers. So, imagine a clock face…
The clock is split into nine: moving clockwise, trialists consider different aspects of the trial.
- Who is chosen to participate in the trial?
- How are they enrolled into the trial?
- Where is the trial being done?
- What expertise and resources are needed to deliver the treatment?
- How should the treatment be delivered?
- What measures are in place to make sure participants comply?
- How closely are participants monitored?
- How relevant is the outcome or result to participants?
- To what extent are all data included?
If, for instance, the people designing the trial think: everyone who might get the treatment in routine care will get into the trial; and they will be invited when they attend a clinic at their usual health centre or hospital; they could be treated by any of the doctors, nurses, physios; and they go back to see the health care professional as often as usual to measure something important eg improve attention in children with Attention Deficit Disorder; then we have a large coloured in clock. If we move away from the norm, then a smaller clock, with less colouring in.
Over eighty international trialists have helped develop this tool to help trialists think through the who, where, how, when of their trial. The “clock” format is very visual – at a glance, you can tell how much a trial equates to the “real world”, how applicable the results of a trial are to usual care; lots of colour then very like the real world and if not much colour then the trial is looking at specific well controlled ideal conditions for particular people or settings. The trial design tool is fun for trial teams to use using paper or the web; a different way of working, improves discussion through making trial teams aware of the range of opinions and facilitates consensus. It aims for consistency in decision making.
Why is this important? Patient and context are key to determine if a trial can answer the question from a patient, doctor or policymaker’s perspective “Does this help me?” An innovative treatment can be the difference between life and death, consequently clinical trials are deadly serious. And expensive – medical research charities invested over 1.3 billion in UK medical research including trials in 2013. Thus, considering trial design and applicability of trial results has never been more important. We owe it to the British taxpayer to improve the health of the British public with well-designed trials and this tool has an apt acronym PRECIS-2. PRECISely when needed, this tool can help design trials from mice to men that are relevant and fit for purpose.
- PRECIS-2 website www.PRECIS-2.org;
- Article in BMJ http://www.bmj.com/content/350/bmj.h2147.full.pdf+html
- YouTube podcast with Kirsty Loudon and Shaun Treweek https://www.youtube.com/watch?v=Sj7cNCyvHVE
Kirsty Loudon, 7 January 2016
Kirsty Loudon is a Research Fellow with the NMAHP Research Unit at the University of Stirling.
Email: firstname.lastname@example.org Twitter: @
Update of a post published in the College bulletin, University of Aberdeen, July 2015.