Model comparison
All statistical analyses were conducted in RStudio (version 1.4.1717) and R (version 4.0.4). In addition to the aforementioned methods, we also conducted the analysis using a raw model, which directly estimated the treatment effects without any adjustment. In order to assess these methods, we compared the true effect with the results (point estimate and 95% confidence interval) from each model, and calculated the bias, root mean squared error (RMSE) along with coverage and width of 95% confidence interval for the treatment effects. The bias was defined as the average difference between the true value (simulated) and its estimate across the simulation replicates using the original scale for the continuous outcome and the log-transformed scale for the binary and time-to-event outcomes, such as log(HR). RMSE was the square root of the mean squared error (MSE) that was the average squared difference between the true value and its estimate across the simulation replicates. Coverage was the proportion of times the 95% confidence interval of the estimate contained the true value. Width was the average difference between the upper and lower bounds of 95% confidence interval of estimate.