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.

Interventions affecting mortality in critically ill and perioperative patients: A systematic review of contemporary trials

Cabrini L.;
2017-01-01

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.
2017
Anesthesia; Critically ill; Intensive care; Mortality; Perioperative; Randomized clinical trials; RCT; Review; Trials
Baiardo Redaelli, M.; Landoni, G.; Di Sanzo, S.; Frassoni, S.; Sartini, C.; Cabrini, L.; Monti, G.; Scandroglio, M.; Zangrillo, A.; Bellomo, R....espandi
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11383/2087539
 Attenzione

L'Ateneo sottopone a validazione solo i file PDF allegati

Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 13
  • ???jsp.display-item.citation.isi??? 11
social impact