Observational vs randomized: David vs Goliath for thromboprophylaxis in critically ill patients?

Excerpt

The study by Stelfox et al. [1] has several major strengths. First, the authors tailored to each ICU a multicomponent intervention to encourage the use of LMWH for VTE prophylaxis, based on available local resources and involved usual multidisciplinary staff (nurses, physicians, pharmacists). Then, a careful examination of exclusion criteria and patient characteristics confirms that the authors did include an all-round critical care population, as consecutive medical, surgical, and cardiovascular surgical patients admitted to ICUs were included in the study unless they presented with a primary bleeding disorder, neurological disorder, or injury. As a consequence, all patients potentially eligible for pharmacological prophylaxis—12,342 patients from a population of 17,242 patients (72%) admitted to the ICUs—were included in the study. Further, the size of the sample studied is a major determinant of the risk of reporting false negative findings. For example, to detect a difference between two groups of 1% (from 3% to 2%), with an alpha risk of 5%, sample sizes of 6000 and 10,000 patients would respectively allow a 70% and 89% power of the study, as shown in Fig. 1a. In the study by Stelfox et al. [1], the risk of finding no difference when a true difference did exist was very low. The inclusion of 12,342 patients allowed a type II error of 6% for detecting a difference of 1% (from 3% to 2% rate of VTE) between the two groups, corresponding to an elevated power of 94% (Fig. 1b) [1]. This sample size was also enough to conclude an equivalence [9] between groups with an equivalence limit of 1%, with a power of more than 90%. Moreover, the difference-in-difference statistical analysis using interrupted time series analysis with segmented linear regression models was the method of choice to assess the effects of a multicomponent intervention over time [10].

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