title: A multiple imputation strategy for sequential multiple assignment randomized trials.
abstract: Sequential multiple assignment randomized trials (SMARTs) are increasingly being used to inform clinical and intervention science. In a SMART, each patient is repeatedly randomized over time. Each randomization occurs at a critical decision point in the treatment course. These critical decision points often correspond to milestones in the disease process or other changes in a patient's health status. Thus, the timing and number of randomizations may vary across patients and depend on evolving patient-specific information. This presents unique challenges when analyzing data from a SMART in the presence of missing data. This paper presents the first comprehensive discussion of missing data issues typical of SMART studies: we describe five specific challenges and propose a flexible imputation strategy to facilitate valid statistical estimation and inference using incomplete data from a SMART. To illustrate these contributions, we consider data from the Clinical Antipsychotic Trial of Intervention and Effectiveness, one of the most well-known SMARTs to date.
authors.affiliation: Biostatistics Unit, Group Health Research Institute, Seattle, WA, 98101, U.S.A.; Department of Biostatistics, University of Washington, Seattle, WA, 98195, U.S.A.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Shortreed
authors.forename: Eric
authors.initials: E
authors.lastname: Laber
authors.forename: T
authors.initials: T
authors.lastname: Scott Stroup
authors.forename: Joelle
authors.initials: J
authors.lastname: Pineau
authors.forename: Susan A
authors.initials: SA
authors.lastname: Murphy
mesh_terms: D014150:Antipsychotic Agents / Q000627:therapeutic use; D003627:Data Interpretation, Statistical; D003657:Decision Making; D006801:Humans; D008137:Longitudinal Studies; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012044:Regression Analysis; D012559:Schizophrenia / Q000188:drug therapy
chemical_list: D014150:Antipsychotic Agents
keywords: dynamic treatment regimes; individualized treatment; missing data; multiple imputation; sequential multiple assignment randomized trials; treatment policies