The research prioritisation exercise. How LeoPARDS was born.

Dr Robert Orme.
Consultant Intensivist, Cheltenham General Hospital. 

Like many ‘jobbing’ intensivists I had always admired those of us who managed to get involved in serious research and get their names in the big journals. I’d also, on many an occasion, thought of important questions that I felt really needed answering with a proper clinical trial but thought that not being a proven researcher in an academic institution would render this unachievable. That’s where the Intensive Care Society really can help, as my experience of the research prioritisation exercise proves.

In 2007, around 5 patients with severe sepsis and myocardial dysfunction on our ICU in Cheltenham received levosimendan after we’d read of its promise in Andrea Morelli’s paper in Intensive Care Medicine. It seemed to make a dramatic impact and all of our patients survived. 

We felt this drug had the potential to improve outcomes in severe sepsis and so worked together to develop an idea for a clinical trial which we then entered into the 2008 Research Prioritisation Exercise. Having pitched this to the Intensive Care Society the proposal was taken forward as one of 6 for presentation at the SOA meeting in December, with the winning proposal receiving a pump-priming £50,000 grant. When, however, I lost out to Tony Gordon’s VANISH trial proposal, I thought that would be the end of the line.

However, the ICS remained hugely supportive of the idea. With the support of the then director of research, Duncan Young, the trial proposal was discussed with the HTA who didn’t feel a phase 3 clinical trial was the way forward.  However, there was clearly some support and, over the next couple of years ongoing discussions lead to a team of experienced researchers including Tony Gordon, Mervyn Singer, Danny McAuley and Gavin Perkins, plus one novice (me) being assembled to progress a phase 2 trial application. With their help and guidance I developed the trial protocol and Tony took on the role of lead investigator and submitted an application to the NIHR EME (Efficacy and Mechanism Evaluation) programme. Whilst this failed due to our choice of primary endpoint, the NIHR were keen to see a revised application and so with a new primary outcome measure decided upon we re-submitted our application in early-2011. In July 2011 we heard the amazing news that we’d been successful. I was now part of the trial team and a co-investigator on a large research grant! The LeoPARDS trial was up and running.

My involvement with the trial continued, both as part of the trial management team and as a member of the trial steering committee but also as the local PI for my Trust. With Tony’s help I wrote the trial protocol. And in January 2014 we recruited the first of 516 patients to the trial. We finished recruitment in late 2016, and the results were presented at the ESICM LIVES conference in Milan in October 2017 with a simultaneous publication in the NEJM. Little did I think when the idea first sprang into our heads in Cheltenham that 10 years later it would have led to a major RCT and an NEJM paper.

The experience of being part of a major trial was hugely rewarding and educational in so many ways. We have some fantastic researchers here in the UK and I was fortunate enough to work with them and learn from them. There is no doubt that the co-ordinated approach to research in ICM we now have as a result of the ICS’s work has transformed our ability to deliver landmark trials. Critically, the research prioritisation exercise provides the chance to get that research question that you’ve always had listened to by our leading researchers. If, like me, you’ve got an idea then submit a proposal to this year’s research prioritisation exercise. You never know, you might just get it funded and get your name in the NEJM too.