American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Sep 2017
ReviewApplying Precision Medicine to Trial Design Using Physiology: Extracorporeal CO2 Removal for ARDS.
In clinical trials of therapies for acute respiratory distress syndrome (ARDS), the average treatment effect in the study population may be attenuated because individual patient responses vary widely. This inflates sample size requirements and increases the cost and difficulty of conducting successful clinical trials. One solution is to enrich the study population with patients most likely to benefit, based on predicted patient response to treatment (predictive enrichment). ⋯ To support this claim, we simulated the predicted effect of ECCO2R on driving pressure and mortality in a preexisting cohort of patients with ARDS. Our computations suggest that restricting enrollment to patients in whom ECCO2R allows driving pressure to be decreased by 5 cm H2O or more can reduce sample size requirement by more than 50% without increasing the total number of patients to be screened. We discuss potential implications for trial design based on this framework.