No firm evidence that lack of blinding affects estimates of mortality in randomized clinical trials of intensive care interventions: a systematic review and meta-analysis.

OBJECTIVE

To evaluate the effect of blinding on mortality effect estimates in randomized clinical trials (RCTs) in adult intensive care unit (ICU) patients.

STUDY DESIGN AND SETTING

A systematic review and meta-analysis of RCTs reporting mortality effect estimates of ICU interventions in adult ICU patients. We assessed differences in summarized risk ratios with 95% confidence intervals between blinded and unblinded RCTs. P < 0.10 was considered statistically significant (test of interaction).

RESULTS

We included 22 ICU interventions assessed in 269 RCTs enrolling a total of 42,007 adult ICU patients in the primary analyses. We observed statistically significant differences between blinded and unblinded RCTs for all-cause mortality at longest follow-up in one of 22 interventions (5%), for in-hospital mortality in one of 12 interventions (8%) but not for in-ICU mortality. Combining all interventions, unblinded trials reported larger summary effect estimates on all-cause mortality at longest follow-up compared to blinded trials (test of interaction, P = 0.09). However, the difference was not statistically significant following adjustment for other risk of bias domains.

CONCLUSIONS

We observed no firm evidence that lack of blinding affects estimates of mortality in RCTs of ICU interventions.