Addressing Missing Outcome Data in Randomised Controlled Trials: A Methodological Scoping Review

Background: Missing outcome data is common in trials, and robust methods to address this are needed. Most trial reports currently use methods applicable under a missing completely at random assumption (MCAR), although this strong assumption can often be inappropriate.

Objective: To identify and summarise current literature on the analytical methods for handling missing outcome data in randomised controlled trials (RCTs), emphasising methods appropriate for data missing at random (MAR) or missing not at random (MNAR).

Study Design And Setting: We conducted a methodological scoping review and identified papers through searching four databases (MEDLINE, Embase, CENTRAL, and CINAHL) from January 2015 to March 2023. We also performed forward and backward citation searching. Eligible papers discussed methods or frameworks for handling missing outcome data in RCTs or simulation studies with an RCT design.

Results: From 1878 records screened, our search identified 101 eligible papers. 90 (89%) papers described specific methods for addressing missing outcome data and 11 (11%) described frameworks for overall methodological approach. Of the 90 methods papers, 30 (33%) described methods under the MAR assumption, 48 (53%) explored methods under the MNAR assumption and 11 (12%) discussed methods under a hybrid of MAR and MNAR assumptions. Control-based methods under the MNAR assumption were the most common method explored, followed by multiple imputation under the MAR assumption.

Conclusion: This review provides guidance on available analytic approaches for handling missing outcome data, particularly under the MNAR assumption. These findings may support trialists in using appropriate methods to address missing outcome data.