Table 6.

Methodologic Recommendations for Acute Respiratory Distress Syndrome Research

	Summary of Methodologic Recommendations	Illustrative Examples
Precision medicine	• Dissect the clinical syndrome of ARDS into the underlying subphenotypes or endotypes and test interventions targeted at biological pathways	• A trial comparing the efficacy of multiple interventions based on biomarkers and clinical outcomes among critically ill adults with a specific ARDS phenotype
Preclinical models	• Develop preclinical models of ARDS that better represent human disease	• Blinded, randomized trial of interventions in large-animal models that recapitulate ARDS etiology and biology in humans and subsequent treatment
Biomarker development	• Develop reliable biomarkers of prognosis and treatment response to bridge from preclinical research to late-phase clinical trials	• Research using preclinical models and existing or prospective human studies to understand and validate the role of specific molecules in the development, progression, and resolution of ARDS
Novel research designs	• Employ novel trial designs and leverage the EHR to improve the efficiency of ARDS clinical trials	• Cluster-randomized trial using electronic health records to identify potential participants, monitor delivery of the intervention, and continuously transmit curated, deidentified data to a coordinating center
Long-term outcomes	• Develop and incorporate a core set of long-term patient-important outcomes into ARDS clinical trials to improve understanding of patient trajectory, acute illness, and recovery	• Trial comparing a novel intervention with current clinical care with regard to long-term patient-important outcomes

Definition of abbreviations: ARDS = acute respiratory distress syndrome; EHR = electronic health record.