The First Controlled Clinical Experiment
One of the first controlled trials is ascribed to James Lind, during an ocean voyage in 1747. Lind, a Scottish physician, thought citrus fruit could cure scurvy, then a major problem amongst sailors during months-long journeys.
Lind divided allocated twelve sailors wirth scurvy into six groups of two. They all received the same diet but, in addition, group one was given a quart of cider daily, group two twenty-five drops of elixir of vitriol (sulfuric acid), group three six spoonfuls of vinegar, group four half a pint of seawater, group five received two oranges and one lemon, and the last group a spicy paste plus a drink of barley water. The treatment of group five stopped after six days when they ran out of fruit, but by that time one sailor was fit for duty while the other had almost recovered. Apart from that, only group one also showed some effect of its treatment.
REMAP-CAP is a modern randomised controlled trial design featuring many elements which improve on the foundations of frequentist trials. In addition, it has a sleeper function, ready to be rapidly activated during a pandemic.
The act of randomly allocating study participants to different groups allows for causation to be inferred
The clinical trial is embedded into routine clinical practice, making it easier for patients to benefit from involvement in clinical trials, while clinical practice benefits from the results generated by the trials
Patients can be entered into multiple domains and receive more than one trial intervention. REMAP-CAP relies on a complex Bayesian framework to achieve this
As the trial progress and data accumulates, randomisation becomes adaptive, meaning future participants become more likely to receive the presently most beneficial intervention
Community-acquired pneumonia is the "platform" condition upon which the entire REMAP-CAP trial is based
Prof Alistair Nichol (Dublin & Melbourne) discusses the latest controversial investigative agent to be added to the REMAP-CAP platform trial - ivermectin
Dr Lennie Derde (Utrecht) talks about the running of the REMAP-CAP trial, including her roles as Chair of the international Trial Steering Committee and European Coordinating Investigator
Prof Derek Angus (Pittsburgh) discusses the concept of a learning healthcare system and how this relates to the REMAP-CAP trial
Prof Alistair Nichol (Dublin & Melbourne) discusses the new ventilator domain soon to be launched as part of the greater REMAP-CAP trial
Prof Mathias Schultz from Jena, Germany, discusses pandemics, the current coronavirus pandemic, and the role of the REMAP-CAP trial in combating this global threat
Srin Murthy and John Marshall from Canada discuss the interventiosns chosen to be tested in the REMAP-CAP adaptive platform trial
Scott Berry, from Berry Consulting, describes the phenomenal Bayesian framework which underlies the complexity of this groundbreaking trial design
Steve Webb, one the original investigators, recounts the origins and growth of REMAP-CAP, including the constant addition of new investigators and sites to the REMAP-CAP Family