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Title: Why don't multicenter randomized controlled trials (RCT) confirm the positive findings of single center RCTs in acute care? (Zeno's Paradox of the Tortoise and Achilles revisited).
Authors: Landoni, Giovanni;Pieri, Marina;Young, Paul J;Bellomo, Rinaldo
Affiliation: School of Medicine, The University of Melbourne, Melbourne, Australia
Australian and New Zealand Intensive Care Research Centre, Monash University School of Public, Clayton, Australia
Health and Preventive Medicine, Melbourne, Australia
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
Vita-Salute San Raffaele University, Milan, Itay
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Itay
Medical Research Institute of New Zealand, Wellington, New Zealand
Intensive Care Unit, Wellington Hospital, Wellington, New Zealand
Department of Intensive Care, Austin Health, Heidelberg, Victoria, Australia
Department of Intensive Care, Royal Melbourne Hospital, Melbourne, Australia
Issue Date: 30-Oct-2018
EDate: 2018-10-30
Citation: Minerva anestesiologica 2018; online first: 30 October
Abstract: It is a common observation that many multicenter randomized controlled trials (mRCT) performed in critically ill patients do not achieve the positive findings often seen in single centre studies (sRCT). This has, of course, relevant consequences for clinical practice, as mRCTs have higher scientific validity compared to sRCTs. The aim of this manuscript was to review and discuss the several potential causes of this phenomenon and to relate them to the future of mRCTs in critical care medicine. Overall, this seems to recall the old mythologic story of Achilles and the tortoise: although mRCTs (i.e. Achilles) are much more powerful, indeed, they always arrive later in time compared to the sRCTs (i.e. the tortoise) from which they were powered. However, sRCTs are more prone to several bias compared to mRCTs, such as local effect bias, selection and performance bias, detection and reporting bias, analysis and attrition bias, concomitant therapy bias, low fragility index and publication bias. In this sense, it is high time the critical care community should see the positive findings of sRTCs with a very high level of scientific caution, unless they are confirmed by mRCTs. MRCTs represent the final step of the process of evidence based medicine and in the end (however slowly and painfully) such evidence catches up with sRCT and truly helps changes practice worldwide.
DOI: 10.23736/S0375-9393.18.13070-7
ORCID: 0000-0002-1650-8939
PubMed URL: 30394068
Type: Journal Article
Appears in Collections:Journal articles

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