Martina Baiardo Redaelli1, Giovanni Landoni2, Stefania Di Sanzo3, Samuele Frassoni4, Chiara Sartini5, Luca Cabrini6, Giacomo Monti7, Mara Scandroglio8, Alberto Zangrillo9, Rinaldo Bellomo10. 1. Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: baiardoredaelli.martina@hsr.it. 2. Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. Electronic address: landoni.giovanni@hsr.it. 3. Department of Cardiac Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy. 4. Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: s.frassoni1@campus.unimib.it. 5. Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy. 6. Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: cabrini.luca@hsr.it. 7. Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: monti.giacomo@hsr.it. 8. Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: scandroglio.mara@hsr.it. 9. Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. Electronic address: zangrillo.alberto@hsr.it. 10. Faculty of Medicine, University of Melbourne, Melbourne, Australia. Electronic address: Rinaldo.BELLOMO@austin.org.au.
Abstract
PURPOSE: Confounders in randomized controlled trials (RCTs) reporting significant effects on mortality in critically ill patients using non-surgical techniques have not been systematically explored. We aimed to identify factors unrelated to the reported intervention that might have affected the findings and robustness of such trials. METHODS: We searched Pubmed/MEDLINE for all RCTs on any non-surgical interventions reporting an effect on unadjusted mortality in critically ill patients between 1/1/2000 and 1/12/2015. We assessed: the number needed to treat/harm (NNT or NNH), sample size, trial design (blinded/unblinded, single or multinational, single or multicenter (sRCT or mRCT)), intention to treat (ITT) analysis, and countries of origin. RESULTS: Almost half of RCTs were sRCTs. Median sample size was small, and 1/3 were not analyzed according to ITT principle. Lack of ITT analysis was associated with greater effect size (p=0.0028). Harm was more likely in mRCTs (p=0.002) and/or in blinded RCTs (p=0.003). Blinded RCTs had double sample size (p=0.007) and an increased NNT/NNH (p=0.002). Finally, mRCTs had higher NNT (p=0.005) and NNH (p=0.02), and harm was only detected in studies from Western countries (p=0.007). CONCLUSIONS: These observations imply that major systematic biases exist and affect trial findings irrespective of the intervention being studied.
PURPOSE: Confounders in randomized controlled trials (RCTs) reporting significant effects on mortality in critically illpatients using non-surgical techniques have not been systematically explored. We aimed to identify factors unrelated to the reported intervention that might have affected the findings and robustness of such trials. METHODS: We searched Pubmed/MEDLINE for all RCTs on any non-surgical interventions reporting an effect on unadjusted mortality in critically illpatients between 1/1/2000 and 1/12/2015. We assessed: the number needed to treat/harm (NNT or NNH), sample size, trial design (blinded/unblinded, single or multinational, single or multicenter (sRCT or mRCT)), intention to treat (ITT) analysis, and countries of origin. RESULTS: Almost half of RCTs were sRCTs. Median sample size was small, and 1/3 were not analyzed according to ITT principle. Lack of ITT analysis was associated with greater effect size (p=0.0028). Harm was more likely in mRCTs (p=0.002) and/or in blinded RCTs (p=0.003). Blinded RCTs had double sample size (p=0.007) and an increased NNT/NNH (p=0.002). Finally, mRCTs had higher NNT (p=0.005) and NNH (p=0.02), and harm was only detected in studies from Western countries (p=0.007). CONCLUSIONS: These observations imply that major systematic biases exist and affect trial findings irrespective of the intervention being studied.
Authors: Alessandro Putzu; Carolina Maria Pinto Domingues de Carvalho E Silva; Juliano Pinheiro de Almeida; Alessandro Belletti; Tiziano Cassina; Giovanni Landoni; Ludhmila Abrahao Hajjar Journal: Ann Intensive Care Date: 2018-09-27 Impact factor: 6.925