Estimands and estimators of two-level methods using return to baseline strategy for longitudinal clinical trials with incomplete daily patient reported outcomes.

ABSTRACT

Returning to baseline (RTB) has been a practical method for handling missing data. Here we consider longitudinal clinical trials with daily patient reported outcomes (PROs), where efficacy endpoints are often defined as the average daily values in a cycle (such as a month or a week). The conventional method treats data at cycle level and ignores daily values. In this paper, we build a two-level constrained longitudinal data analysis (cLDA) model on daily values and propose two-level RTB method to impute daily values. Standard multiple imputation (MI) approach and likelihood-based approach are proposed and evaluated by simulations.