Abstract: In clinical trials with multiple visits, dropouts often occur and the population of patients who dropped out may be different from the population of patients who completed the study. To assess treatment effects over the population of all randomized patients, which is called the intention-to-treat analysis and is required by regulatory agencies, last observation analysis (LOAN) focuses on the last observation of each patient prior to dropout. As a type of LOAN, the last observation carry-forward (LOCF) method treats the last observation prior to dropout as the missing observation at the end of the trial and applies standard tests designed for the case of no dropout. Regulatory agencies such as the U.S. Food and Drug Administration (FDA) have expressed concerns about the validity of the LOCF methods. In this paper we study the validity of LOAN and LOCF tests under an analysis of covariance model, which includes the analysis of variance model as a special case. In situations where LOAN is relevant, we provide explicit conditions under which LOCF tests are asymptotically valid and we derive asymptotically valid tests when LOCF tests are invalid.
Key words and phrases: Dropout, intention-to-treat analysis, last observation carry-forward, balanced design, balanced covariates.