• ARDS
• Critical Care

It is not a novel observation that the clinical trial enterprise has largely been unsuccessful in finding new and effective treatments for the acute respiratory distress syndrome (ARDS).1 2 While a significant contributor to the absence of success may be the testing of ineffective treatments, other likely contributors include selecting the wrong population and having unrealistic expectations about the possible effect of the treatment on the outcomes, most often risk of death or duration of ventilatory support.

In common with sepsis, ARDS is not a disease but rather a syndrome characterised by heterogeneity at many levels. This includes recognisable heterogeneity such as the precipitating insult and the trial participants’ phenotype (eg, age, baseline frailty and comorbidities) and less overt heterogeneity such as genotype and the biology of ARDS itself.3

Even when a trial intervention is beneficial in at least some patients with ARDS, confirming that beneficial effect in a randomised clinical trial (RCT) is critically dependent on selecting the correct participants. The likelihood of enrolling the ‘correct’ participants is increased by appropriate use of enrichment strategies.2 Predictive enrichment refers to selectively enrolling a subpopulation of patients who have an increased likelihood of responding to the test treatment, an example of which might be selecting patients with ARDS with a hyperinflammatory phenotype in studying the effect of simvastatin.4 Prognostic …