Anatomy of a clinical trial – FEAST (2011)
Should you give IV fluid boluses to acutely sick African children, in shock with Malaria, Sepsis, Meningitis and other febrile illnesses? Will it help to help keep them alive until antibiotics, antimalarials or other treatments kick in? Twenty years of medical practice said you should, that fluid resuscitation can cheat death and buy time. But this large Randomized Controlled Clinical trial (3000+ children across seven sites), the only ever done to evaluate fluid resuscitation in children, found fluid boluses to be harmful resulting in higher mortality. It was true of all febrile illnesses tested in the trial and all definitions of shock. But despite only low quality evidence to support fluid resuscitation, seven years later the FEAST results remain hugely controversial.
These two films use the FEAST Trial to lay open the workings of a randomised controlled clinical trial. In FEAST the staff running the trial were able to see which children received fluid boluses and which did not. They consistently noticed that symptoms of shock improved in children who received boluses. Arms and legs warmed up. Sometimes children even came out of a coma. It was similar experience recorded in previous observational studies that had led to the adoption of fluid resuscitation for children in shock and led to it becoming worldwide standard practice for over twenty years. So when asked on camera to predict the result of the trial, the FEAST staff almost all believed that fluid boluses would be beneficial. In fact the trial showed the opposite – that the improvement in symptoms did not translate to less deaths. On the contrary, the trial was stopped early with a statistically significant result showing harm. The disbelief shown in the film on the faces of the nurses and doctors who ran the study at being told the result, was echoed in the wider medical community, resulting in a long and sometimes heated debate about the future of fluids in emergency children’s medicine.
This first film tells the story of a major clinical trial which set out to show that a central tenet of children’s emergency medicine in the first world, could be safely rolled out in Africa. In fact it showed fluid resuscitation to be harmful, calling into question previous low quality observational evidence upon which 20 years of clinical practice had been built.
The second film, narrated by the FEAST trial manager, focuses more closely on the workings of a randomised controlled clinical trial. It shows why this is the best quality of evidence, and why observational evidence cannot always differentiate between improvement of symtoms and real benefit. This would be good viewing for anyone interested in medical research.