Prioritising the Research Agenda for Trial Retention – Birmingham, 23rd October 2018

I’ve been in Birmingham today for the final consensus meeting of the PRioRiTy II project, so I thought I’d write a quick blog post before dinner so that you can find out a bit more about the process of research prioritisation.

Image credit: Prof Shaun Treweek

I’ve spoken on this blog before about the first PRioRiTy project, which was a prioritisation of questions around trial recruitment. That project took the same shape, though I’ve been more heavily involved in PRioRiTy II because it’s led by Dr Katie Gillies, who was one of my PhD supervisors; she’s now one of my line managers and she’s fantastic to work with. Katie was a participant in the consensus meeting for PRioRiTy, and as soon as she came back from that meeting (almost 2 years ago!), she set to work on PRioRiTy II – she moves fast because she is a complete trial methods nerd, just like me (I’ve found my people!).

So, I said she moves fast, but you might ask why it’s taken 2 years to get here. As with anything in research the process is not as simple as it looks. This prioritisation exercise was not simply a group of people getting together in a room today and deciding what we thought was most important; the process has involved many, many more people than just those in the room, and is based on the method that the James Lind Alliance (JLA) use for priority setting partnerships. The JLA method is designed to take into account the views and opinions of all stakeholders that have an interest in a specific research area. For us, that meant: trialists, methodologists, ethics committee members, researchers, patients, funders, clinicians and more, but the JLA method has been used for lots of prioritisation activities and the people involved are tailored each time to fit with the aims of the project.

We had a wonderful graphic illustrator with us today, and she captured the ‘story so far’ brilliantly in the image below. Before today we had a survey, followed by a huge amount of data analysis and question searching within the responses from that initial survey, an interim prioritisation process (some of you might have been involved with this because I posted about it here), and then came this face to face consensus meeting – so today was the culmination of a lot of views, opinions, time and effort.

A snapshot of a graphic illustration from the PRioRiTy II consensus meeting showing the story so far.

Below are a few photographs from the day – lots of serious faces, extensive discussion, and some compromises needing to be made too.

The kick off – Katherine Cowan (Senior Advisor to the JLA) did an excellent job chairing the workshop, keeping us all to time and making sure that everyone’s voice was heard within the discussions.

Image credit: Prof Shaun Treweek

In the first session of group work attendees shared their 3 most and 3 least important questions from the list of 21 that we had supplied them with in advance. From the initial survey responses we had 27 questions, which were then narrowed down to 21 questions during the interim prioritisation.

The second session of group work saw the beginning of the ranking process! Coloured tablecloths were used to distinguish questions that were most important (green), least important (red), and somewhere in the middle (yellow). This allowed participants to discuss the ranking of their group as a whole (i.e. based on the feedback from the first group session), and then physically move the questions into a more defined ranking position after discussion.

The final session – questions were laid on the floor so that the entire group could see the ranking. Katherine then went through each question in turn to ensure that the group could reach a consensus; harder than you might think!

Image credit: Trial Forge

We won’t be sharing the top 10 questions around trial retention just yet though; tomorrow we have our final Steering Group meeting (let me know if you’d like to see a blog post about what a Steering Group does within a research project!) where we will go through the top 20 questions and make sure that all the wording is clear.

We then plan on unveiling the top 10 at the Society of Clinical Trials meeting in New Orleans next May. If you’ve been reading the blog for a while you might remember that I went to the Society for Clinical Trials meeting earlier this year when it was in Portland. It’s a brilliant conference that enables trialists from around the world to meet each year to share their work. After that we also plan to do some more conference dissemination at the International Clinical Trials Methodology conference, which takes place in Brighton next October. Keep an eye out for future blog posts too – I’ll be posting the final top 10 when they’re released!

Image credit: Prof Jane Daniels

When Was the First Clinical Trial?

As you’ve probably (hopefully!) picked up from other posts on this blog, my research is centred around clinical trials and their methodology. Trials can be intimidating for people that don’t know a whole lot about them, and as I’ve mentioned before, the ‘guinea pig‘ concept seems to haunt trial participation.

In this series of posts I want to answer any questions people have – from the basic to the obscure and everything in between – and demystify clinical trials. I asked a few friends who don’t work in a trials environment what they don’t know about trials, and the obvious starting point was ‘when was the first clinical trial?’, so here we are. Read on to find out when and how and first clinical trial came about.

Some sources say the first clinical trial was conducted in 605-562 BC, as outlined in the Old Testament’s Book of Daniel. Put simply, King Nebuchagnezzar II ordered the children of royal blood to eat only meat and wine for 10 days. Daniel asked that he and three other children be allowed only to eat vegetables, bread and water. After the 10 days was over, Daniel and the three children were noticeably healthier than the children who had eaten only meat and wine. Whilst this is clearly research (though as Ben Goldacre points out, probably underpowered research), the groups were not controlled. This was probably one of the first times in evolution of human species that an open uncontrolled human experiment guided a decision about public health.

James Lind is credited with the first controlled clinical trial; controlled meaning that his study included a comparison, or control, group. The comparison group received a placebo, another treatment or no treatment at all. Lind, a Scottish Naval Surgeon, conducted the first controlled clinical trial on the 20th May 1747 on a group of sailors suffering from scurvy.

He included 6 pairs of sailors in his trial; placed them all on the same diet, and then gave each of the pairs an additional intervention. One pair had a quart of cider each day; one pair took 25 drops of elixir vitriol (sulphuric acid) three times a day; one pair had 2 spoonfuls of vinegar three times a day; one pair were put on what Lind describes as a ‘course of sea-water’; one pair each had 2 oranges and 1 lemon given to them each day; and another had what’s described as a ‘bigness of a nutmeg’ three times a day.

I know which of the treatments I have preferred at that time (i.e. not a course of seawater!).

At the end of day 6 of Lind’s trial, the pair that had eaten 2 oranges and 1 lemon each day were fit for duty and taking care of the other 5 pairs of sailors. Lind notes in his book ‘Treatise on Scurvy’ (published in Edinburgh in 1753) that he thought after the citrus fruits, the cider had the best effects.

We now know scurvy is caused by a deficiency in vitamin C, hence why fruits rich in vitamin C had his sailors fighting fit again after just 6 days.

Clinical trials like James Lind’s are what we base our current practice on. Over the years since Lind found the cure for scurvy, huge advances have been made in the methodology of trials; we now have placebos, use randomisation, adhere to various codes of conduct, and work with huge groups of patients and teams of research staff across the world in an effort to answer clinical questions.

This is the first post in a series I’m calling ‘Clinical Trials Q&A’. If you have any questions about clinical trials, what they are, why we do them, what their limitations are.. etc, please pop them in a comment or tweet me @heidirgardner and I’ll be sure to answer them in upcoming blog posts.