Earlier this year in the CHEST magazine, four renowned critical care physicians from Spain and the US published an opinion piece „ARDS – Lessons Learned From the Heart“. The Acute Respiratory Distress Syndrome (ARDS, sometimes referred to as Shock Lung), was first described in 1967. Bringing death to many affected patients, the condition was extensively studied since, with multiple million-dollar clinical studies trying to find a cure, conducted in hundreds of hospitals all over the world especially during the last two decades.
The authors describe that many conditions can lead to ARDS and wonder whether ARDS is a distinct clinical entity at all. They raise their disappointment about the multitude of failed studies from the past decades, and postulate to focus on distinct endophenotypes of patients, such as those with diffuse alveolar damage (DAD). No doubt they are right – and it is high time such insights start to spread.
Unfortunately, while „ARDS“ comes in handy as a four letter acronym, and the scientific community as well as regulators used to believe to finally have a grasp on the condition – it wasn’t quite that easy. In reality, experts knew early on that this syndrome can be caused by many underlying conditions.
Doubts around the suitability of „ARDS“ as enrollment criterion for clinical studies were raised already in the 1990s. Let me give just two examples. Mark Palazzo and Neil Soni published their visionary viewpoint „Critical-care studies: redefining the rules“ in THE LANCET in 1998. They had recognized that trials should study patients with common underlying conditions (insults) rather that the patients‘ responses, such as sepsis or ARDS.
We propose that critical-care trial designs are radically changed
(Palazzo, Soni, 1998)
In 2001, the UK Medical Research Council International Working Party lead by Jonathan Cohen has, in the CRITICAL CARE MEDICINE journal, initiated a comprehensive discussion titled „New Strategies for Clinical Trials in Patients with Sepsis and Septic Shock“, a treasure trove for all who have the ambition to think twice when designing critical care studies.
Working in critical care research since those times, I have been astonished to observe how little recognition these and several other intelligent articles have found. Many academic and industry studies have simply ignored known facts – and have forseeably failed.
The fatal consequences: On one hand, therapeutic progress for critically ill patients was not what it could have been. On the other, lots of scarce research money was wasted. And, on top, is it ethical to ask patients for participation in clinical trials which are almost certain to fail, because they repeat well identified mistakes?
Coming back to the 2015 CHEST piece – it is wonderful that the word seems to spread. Better late than never. And now let’s apply the wealth of knowledge and experience on how to conduct critical care studies. We owe it to our patients.