Impute the missing data by combining retrieved dropouts and return to baseline method

Currently, various methods have been proposed to handle missing data in clinical trials. Some methods assume that the missing data are missing at random (MAR), which means that it is assumed that subjects who stopped treatment would still maintain the treatment effect. In many cases, however, researchers often assume that the missing data are missing not at random (MNAR) to conduct additional sensitivity analyses. Under the MNAR assumption, whether using some conservative imputation methods such as RTB (return to baseline) method, J2R (jump to reference) method, and CR (copy reference) method, or optimistic imputation methods like multiple imputation (MI) and its derivative RD (retrieved dropout) method, biases compared to the true treatment effect can occur in some scenarios. This paper aims to propose a method that can impute results while considering the occurrence of intercurrent events, thereby reducing the bias compared to the true treatment effect. This method combines the RD method with the RTB formula, reducing the biases and standard errors associated with using either method alone. Considering the differing treatment effects between RD subjects and non-RD subjects, our imputation results often align more closely with the true drug efficacy.