The impact of non-blinding in critical care medicine trials

Purpose: It is uncertain whether, in critical care medicine, non-blinded trials are associated with a bias toward a different effect size. The aim of our study was to assess if conducting non-blinded/open label studies leads to greater effect size than blinded studies, and to provide an estimate of the weight of this difference. Materials and methods: We systematically searched all papers published in peer-reviewed journals between January 2000 and December 2015, dealing with non surgical interventions in critically ill adults and reporting a statistically significant difference in mortality. We assessed the number needed to treat (NNT) of each trial to estimate the treatment effect size and we divided studies into non-blinded, single-blinded and double-blinded. We searched for correlation between the treatment effect size and blinding, and adjusted for the other trial variables. Results: We identified 119 critically ill randomized controlled trials. Of these, 69 studies were non-blinded and 50 were blinded. The median NNT in non-blinded studies was 5 [IQR 4–7] while it was 7 [IQR 5–7] in the blinded studies (p <.001). Conclusions: The NNT for blinded studies is 40% higher than for unblinded studies. This should be taken into account when planning and interpreting the findings of non-blinded studies performed in critically ill settings.