title: Physiologic Responsiveness Should Guide Entry into Randomized Controlled Trials.
abstract: Most randomized trials in critical care report no mortality benefit; this may reflect competing pathogenic mechanisms, patient heterogeneity, or true ineffectiveness of interventions. We hypothesize that in acute respiratory distress syndrome (ARDS), randomizing only those patients who show a favorable physiological response to an intervention would help ensure that only those likely to benefit would be entered into the study. If true, this would decrease study "noise" and reduce required sample size, thereby increasing the chances of finding true-positive outcomes. It would also lessen the chances of exposing patients to treatments that are unlikely to help or that could cause harm. We present a reanalysis of randomized clinical trials of positive end-expiratory pressure in ARDS that support this hypothesis.
authors.affiliation: 1 Interdepartmental Division of Critical Care Medicine.|3 Department of Medicine.|4 Department of Physiology.|2 Division of Respirology, Department of Medicine, University Health Network and Mount Sinai Hospital, Toronto, Canada.
authors.forename: Ewan C
authors.initials: EC
authors.lastname: Goligher
authors.affiliation: 1 Interdepartmental Division of Critical Care Medicine.|3 Department of Medicine.|4 Department of Physiology.|5 Department of Anesthesia.|6 Department of Critical Care Medicine, Hospital for Sick Children, Toronto, Canada.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Kavanagh
authors.affiliation: 1 Interdepartmental Division of Critical Care Medicine.|3 Department of Medicine.|8 Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Canada.|7 Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, Canada.
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Rubenfeld
authors.affiliation: 1 Interdepartmental Division of Critical Care Medicine.|3 Department of Medicine.|4 Department of Physiology.|8 Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Canada.|2 Division of Respirology, Department of Medicine, University Health Network and Mount Sinai Hospital, Toronto, Canada.
authors.forename: Niall D
authors.initials: ND
authors.lastname: Ferguson
mesh_terms: D003422:Critical Care; D006801:Humans; D018579:Patient Selection; D011175:Positive-Pressure Respiration; D016032:Randomized Controlled Trials as Topic; D012128:Respiratory Distress Syndrome / Q000503:physiopathology* / Q000628:therapy*; D012129:Respiratory Function Tests / Q000706:statistics & numerical data; D013990:Tidal Volume / Q000502:physiology