TY - JOUR
T1 - Mortality in multicenter critical care trials
T2 - An analysis of interventions with a significant effect
AU - Landoni, Giovanni
AU - Comis, Marco
AU - Conte, Massimiliano
AU - Finco, Gabriele
AU - Mucchetti, Marta
AU - Paternoster, Gianluca
AU - Pisano, Antonio
AU - Ruggeri, Laura
AU - Alvaro, Gabriele
AU - Angelone, Manuela
AU - Bergonzi, Pier C.
AU - Bocchino, Speranza
AU - Borghi, Giovanni
AU - Bove, Tiziana
AU - Buscaglia, Giuseppe
AU - Cabrini, Luca
AU - Callegher, Lino
AU - Caramelli, Fabio
AU - Colombo, Sergio
AU - Corno, Laura
AU - Del Sarto, Paolo
AU - Feltracco, Paolo
AU - Forti, Alessandro
AU - Ganzaroli, Marco
AU - Greco, Massimiliano
AU - Guarracino, Fabio
AU - Lembo, Rosalba
AU - Lobreglio, Rosetta
AU - Meroni, Roberta
AU - Monaco, Fabrizio
AU - Musu, Mario
AU - Pala, Giovanni
AU - Pasin, Laura
AU - Pieri, Marina
AU - Pisarra, Stefania
AU - Ponticelli, Giuseppe
AU - Roasio, Agostino
AU - Santini, Francesco
AU - Silvetti, Simona
AU - Székely, Andrea
AU - Zambon, Massimo
AU - Zucchetti, Maria Chiara
AU - Zangrillo, Alberto
AU - Bellomo, Rinaldo
PY - 2015
Y1 - 2015
N2 - Objectives: We aimed to identify all treatments that affect mortality in adult critically ill patients in multicenter randomized controlled trials. We also evaluated the methodological aspects of these studies, and we surveyed clinicians' opinion and usual practice for the selected interventions. Data Sources: MEDLINE/PubMed, Scopus, and Embase were searched. Further articles were suggested for inclusion from experts and cross-check of references. Study Selection: We selected the articles that fulfilled the following criteria: publication in a peer-reviewed journal; multicenter randomized controlled trial design; dealing with nonsurgical interventions in adult critically ill patients; and statistically significant effect in unadjusted landmark mortality. A consensus conference assessed all interventions and excluded those with lack of reproducibility, lack of generalizability, high probability of type I error, major baseline imbalances between intervention and control groups, major design flaws, contradiction by subsequent larger higher quality trials, modified intention to treat analysis, effect found only after adjustments, and lack of biological plausibility. Data Extraction: For all selected studies, we recorded the intervention and its comparator, the setting, the sample size, whether enrollment was completed or interrupted, the presence of blinding, the effect size, and the duration of follow-up. Data Synthesis: We found 15 interventions that affected mortality in 24 multicenter randomized controlled trials. Median sample size was small (199 patients) as was median centers number (10). Blinded trials enrolled significantly more patients and involved more centers. Multicenter randomized controlled trials showing harm also involved significantly more centers and more patients (p = 0.016 and p = 0.04, respectively). Five hundred fifty-five clinicians from 61 countries showed variable agreement on perceived validity of such interventions. Conclusions: We identified 15 treatments that decreased/ increased mortality in critically ill patients in 24 multicenter randomized controlled trials. However, design affected trial size and larger trials were more likely to show harm. Finally, clinicians view of such trials and their translation into practice varied.
AB - Objectives: We aimed to identify all treatments that affect mortality in adult critically ill patients in multicenter randomized controlled trials. We also evaluated the methodological aspects of these studies, and we surveyed clinicians' opinion and usual practice for the selected interventions. Data Sources: MEDLINE/PubMed, Scopus, and Embase were searched. Further articles were suggested for inclusion from experts and cross-check of references. Study Selection: We selected the articles that fulfilled the following criteria: publication in a peer-reviewed journal; multicenter randomized controlled trial design; dealing with nonsurgical interventions in adult critically ill patients; and statistically significant effect in unadjusted landmark mortality. A consensus conference assessed all interventions and excluded those with lack of reproducibility, lack of generalizability, high probability of type I error, major baseline imbalances between intervention and control groups, major design flaws, contradiction by subsequent larger higher quality trials, modified intention to treat analysis, effect found only after adjustments, and lack of biological plausibility. Data Extraction: For all selected studies, we recorded the intervention and its comparator, the setting, the sample size, whether enrollment was completed or interrupted, the presence of blinding, the effect size, and the duration of follow-up. Data Synthesis: We found 15 interventions that affected mortality in 24 multicenter randomized controlled trials. Median sample size was small (199 patients) as was median centers number (10). Blinded trials enrolled significantly more patients and involved more centers. Multicenter randomized controlled trials showing harm also involved significantly more centers and more patients (p = 0.016 and p = 0.04, respectively). Five hundred fifty-five clinicians from 61 countries showed variable agreement on perceived validity of such interventions. Conclusions: We identified 15 treatments that decreased/ increased mortality in critically ill patients in 24 multicenter randomized controlled trials. However, design affected trial size and larger trials were more likely to show harm. Finally, clinicians view of such trials and their translation into practice varied.
KW - Consensus conference
KW - Critically ill patients
KW - Intensive care unit
KW - Multicenter randomized controlled trials
KW - Noninvasive ventilation
KW - Nonsurgical interventions
KW - Treatments to increase and decrease mortality
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UR - http://www.scopus.com/inward/citedby.url?scp=84942512424&partnerID=8YFLogxK
U2 - 10.1097/CCM.0000000000000974
DO - 10.1097/CCM.0000000000000974
M3 - Article
C2 - 25821918
AN - SCOPUS:84942512424
VL - 43
SP - 1559
EP - 1568
JO - Critical Care Medicine
JF - Critical Care Medicine
SN - 0090-3493
IS - 8
ER -