ARDS (acute respiratory distress syndrome), sometimes termed „shock lung“, is a dangerous condition observed in intensive care patients and is associated with a high mortality rate between 20 and 40%. But how frequently is ARDS diagnosed? Is the condition possibly under-diagnosed? I fully understand intensivists who may not be very keen on assigning this diagnosis. Psychologically, there is little upside in assigning it, because no specific treatment is available, but lots of downside, due to this frightening mortality rate.
One of the consequences of under-diagnosing a condition is: reduced interest by pharma managers to invest in developing new therapeutic options, because market forecasters will most likely come up with unattractive market assumptions.
Academic researchers have now joined forces to shed light on epidemiology, patterns of care, and outcome for patients with ARDS (JAMA 2016; 315: 788-800). 29’144 patients receiving invasive or non-invasive ventilation in 459 ICUs in 50 countries around the globe in a consecutive four week period were analyzed. 3022 (10.4%) were found to have ARDS by strict application of the Berlin Criteria, but more than a third of these cases were never assigned the diagnosis of ARDS by the treating physician. This in turn means:
ARDS incidence assumptions based on discharge diagnoses may underestimate the true incidence by an astonishing 50% .
ARDS patients in well controlled studies may be threatened by a mortality rate around 25%. This number, again, seems to substantially underestimate real life mortality from the condition:
We know that 40 per cent of patients with ARDS die, either of this syndrome or their primary illness or injury, so this new, global understanding of this important public health issue is enormously important for patients and clinicians.
Dr. John Laffey, University of Toronto
Higher real-life mortality, compared with clinical studies, has also been reported by Pierrakos and Vincent (Europ Resp J 2012) with ICU mortality in ARDS patients from 1993-1995 at 52% and from 2006 to 2009 at 46%.
And if you take a close look to the LUNG SAFE data, there is an important piece of encouragement for ambitious clinical development projects. Almost 60% of the patients had pneumonia, and 14% had aspiration as underlying cause of ARDS. Since 2004, it is known that patients with direct pulmonary causes of ARDS are better suited for outcome studies of pulmonary interventions, because they have less non-controllable extra-pulmonary reasons to die (statistical „noise“ jeopardizing the „signal“) – see figure below (Spragg: NEJM 2004; 351(9): 884-892).
It can be concluded that it is absolutely feasible to focus clinical studies to patients with pulmonary predispositions (and it has been done already).
So, hopefully more pharma companies, biotechs, and investors will dare to engage in this field, because there are a lot of patients who urgently need new therapies. However, I would discourage anyone from selecting a study population based on the definition of „ARDS“, but that’s another story.
View related post by Friedemann on why ARDS studies notoriously failed during the last decades, and on the promising results of the Lung Safe Study