Identifying molecular subtypes of critical illness to inform better treatments using a precision medicine framework

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Critical illness is an acute illness, from diverse aetiology, resulting in organ dysfunction, necessitating organ support to survive. Clinical, and biological heterogeneity within similar critical illnesses is the norm. More importantly, there are biological commonalities across different critical illnesses. The current paradigm in critical illness is syndromes such as sepsis, pancreatitis, polytrauma and respiratory distress syndrome (ARDS). Recently, in a concept paper, the need to de-emphasise this syndrome based framework used in critical illness to enable precision medicine for critically ill adults was stressed (Maslove et al., 2022).The primary supervisor leads a precision medicine programme to enable a treatable trait approach within critical illness - TRAITS programme. This globally unique research programme consists of data enabled adaptive randomized controlled rials (RCTs) with embedded biological characterization in adult critically ill patents. The RCT adaptation may include selection of new treatments or identification of target sub-groups within traits. In the TRAITS programme, treatable traits are conceptualised as measurable and treatable biological states with distinct biological signatures that are associated with patient outcomes. Lymphopenia with respiratory failure is an example of treatable trait. The underpinning hypothesis of this programme, supported by data, is that treatable traits agnostic of the inciting insult that led to critical illness syndromes occur and that this is a valid approach to enable time-critical precision medicine.Using clinical data, and biological samples from the TRAITS Trial, the aims are to derive, and validate the- Molecular signatures for lymphopenia-respiratory failure trait- Multivariable biomarker profiles that are either highly predictive of treatment responses to one of the treatments tested (Baricitinib or corticosteroids), or of clinical outcomes for critically ill patients with lymphopenia-respiratory failure trait.Maslove, D.M. et al. (2022) 'Redefining critical illness', Nature Medicine, 28(6), pp. 1141-1148. Available at: https://doi.org/10.1038/s41591-022-01843-x.