Challenges of using external data in clinical trials- an illustration in patients with COVID-19.

ABSTRACT

BACKGROUND: To improve the efficiency of clinical trials, leveraging external data on control and/or treatment effects, which is almost always available, appears to be a promising approach. METHODS: We used data from the experimental arm of the Covidicus trial evaluating high-dose dexamethasone in severely ill and mechanically ventilated COVID-19 patients, using published data from the Recovery trial as external data, to estimate the 28-day mortality rate. Primary approaches to deal with external data were applied. RESULTS: Estimates ranged from 0.241 ignoring the external data up to 0.294 using hierarchical Bayesian models. Some evidence of differences in mortality rates between the Covidicus and Recovery trials were observed, with an matched adjusted odds ratio of death in the Covidicus arm of 0.41 compared to the Recovery arm. CONCLUSIONS: These indirect comparisons appear sensitive to the method used. None of those approaches appear robust enough to overcome randomized clinical trial data. TRIAL REGISTRATION Covidicus Trial NCT04344730, First Posted 14/04/2020; Recovery trial NCT04381936.