Between-trial heterogeneity in ARDS research
Intensive Care Medicine, vol. 47, pp. 422–434
Abstract
PURPOSE: Most randomized controlled trials (RCTs) in patients with acute respiratory distress syndrome (ARDS) revealed indeterminate or conflicting study results. We aimed to systematically evaluate between-trial heterogeneity in reporting standards and trial outcome. METHODS: A systematic review of RCTs published between 2000 and 2019 was performed including adult ARDS patients receiving lung-protective ventilation. A random-effects meta-regression model was applied to quantify heterogeneity (non-random variability) and to evaluate trial and patient characteristics as sources of heterogeneity. RESULTS: = 88%, p < 0.0001). Reported baseline patient characteristics explained some of the outcome heterogeneity, but only six trials (9%) reported all four independently predictive variables (mean age, mean lung injury score, mean plateau pressure and mean arterial pH). The 28-day control group mortality adjusted for patient characteristics (i.e. the residual heterogeneity) ranged from 18 to 45%. Trials with significant benefit in the primary outcome reported a higher control group mortality than trials with an indeterminate outcome or harm (mean 28-day control group mortality: 44% vs. 28%; p = 0.001). CONCLUSION: Among ARDS RCTs in the lung-protective ventilation era, there was large variability in the description of baseline characteristics and significant unexplainable heterogeneity in 28-day control group mortality. These findings signify problems with the generalizability of ARDS research and underline the urgent need for standardized reporting of trial and baseline characteristics.
Authors 8
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Jenny Juschten corresponding
Amsterdam University Medical Centers · Vrije Universiteit Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Anesthesiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. j.juschten@amsterdamumc.nl
Department of Intensive Care, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, mail stop ZH 7D-172, 1081HV, Amsterdam, The Netherlands. j.juschten@amsterdamumc.nl
Research VUmc Intensive Care (REVIVE), Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. j.juschten@amsterdamumc.nl
Department of Intensive Care, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, mail stop ZH 7D-172, 1081HV, Amsterdam, The Netherlands
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Amsterdam University Medical Centers · Vrije Universiteit Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Intensive Care, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, mail stop ZH 7D-172, 1081HV, Amsterdam, The Netherlands
Research VUmc Intensive Care (REVIVE), Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
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Tingjie Guo Aachen Division of System Biomedicine and Pharmacology Leiden Academic Centre for Drug Research
Leiden University · Amsterdam University Medical Centers · Vrije Universiteit Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Intensive Care, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, mail stop ZH 7D-172, 1081HV, Amsterdam, The Netherlands
Division of System Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden, The Netherlands
Research VUmc Intensive Care (REVIVE), Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
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OLVG · Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Department of Intensive Care, OLVG Hospital, Amsterdam, The Netherlands
Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), Amsterdam UMC, Universiteit Van Amsterdam, Amsterdam, The Netherlands
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Mahidol University · University of Oxford · Mahidol Oxford Tropical Medicine Research Unit · Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Department of Intensive Care, Amsterdam UMC, Universiteit Van Amsterdam, Amsterdam, The Netherlands
Mahidol-Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand
Nuffield Department of Medicine, University of Oxford, Oxford, UK
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Amsterdam University Medical Centers · Vrije Universiteit Amsterdam
Affiliation as printed
Department of Anesthesiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
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Amsterdam University Medical Centers · Vrije Universiteit Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Intensive Care, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, mail stop ZH 7D-172, 1081HV, Amsterdam, The Netherlands
Research VUmc Intensive Care (REVIVE), Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
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Amsterdam University Medical Centers · Vrije Universiteit Amsterdam
Affiliation as printed
Department of Anesthesiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
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