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Emulating target trials using observational data

An application to estimating mortality of delays in appropriate antibiotic treatment and accounting for time-varying confounding and immortal time biases

Delays in treating bacteraemias with antibiotics to which the causative organism is susceptible are expected to adversely affect patient outcomes. However, the extent of the impact remains to be elucidated. This cannot ethically be addressed in a randomised trial. Therefore, an observational cohort study is likely to be the best alternative approach to determine the impact of delays in concordant antibiotic treatment on patient outcomes. There are, however, potentially important biases to be addressed, including time-varying confounding effect and immortal time bias. 

We described two target trials, and performed analyses on observational data aiming, as far as possible, to emulate the trials. Among 1,203 patients with Acinetobacter species hospital-acquired bacteremia in a tertiary hospital in Thailand, 682 had ≥1 days of delays to concordant treatment. Surprisingly, crude 30-day mortality was lower in patients with delays of ≥3 days compared with those who had 1–2 days of delays. Accounting for confounders and immortal time bias resolved this paradox. Emulating a target trial, we found that these delays were associated with an absolute increase in expected 30-day mortality of 6.6% (95% confidence interval: 0.2, 13.0), from 33.8% to 40.4%.


Dr Cherry Lim, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Thailand 


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