title: Comparing dynamic treatment regimes using repeated-measures outcomes: modeling considerations in SMART studies.
abstract: A dynamic treatment regime (DTR) is a sequence of decision rules, each of which recommends a treatment based on a patient's past and current health status. Sequential, multiple assignment, randomized trials (SMARTs) are multi-stage trial designs that yield data specifically for building effective DTRs. Modeling the marginal mean trajectories of a repeated-measures outcome arising from a SMART presents challenges, because traditional longitudinal models used for randomized clinical trials do not take into account the unique design features of SMART. We discuss modeling considerations for various forms of SMART designs, emphasizing the importance of considering the timing of repeated measures in relation to the treatment stages in a SMART. For illustration, we use data from three SMART case studies with increasing level of complexity, in autism, child attention deficit hyperactivity disorder, and adult alcoholism. In all three SMARTs, we illustrate how to accommodate the design features along with the timing of the repeated measures when comparing DTRs based on mean trajectories of the repeated-measures outcome.
authors.affiliation: The Pennsylvania State University, State College, PA, U.S.A.
authors.forename: Xi
authors.initials: X
authors.lastname: Lu
authors.affiliation: University of Michigan, Ann Arbor, MI, U.S.A.
authors.forename: Inbal
authors.initials: I
authors.lastname: Nahum-Shani
authors.affiliation: University of California, Los Angeles, Los Angeles, CA, U.S.A.
authors.forename: Connie
authors.initials: C
authors.lastname: Kasari
authors.affiliation: University of Pennsylvania, Philadelphia, PA, U.S.A.
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Lynch
authors.affiliation: University of Pennsylvania, Philadelphia, PA, U.S.A.
authors.forename: David W
authors.initials: DW
authors.lastname: Oslin
authors.affiliation: Florida International University, Miami, FL, U.S.A.
authors.forename: William E
authors.initials: WE
authors.lastname: Pelham
authors.affiliation: University at Buffalo, the State University of New York, Buffalo, NY, U.S.A.
authors.forename: Gregory
authors.initials: G
authors.lastname: Fabiano
authors.affiliation: University of Michigan, Ann Arbor, MI, U.S.A.
authors.forename: Daniel
authors.initials: D
authors.lastname: Almirall
mesh_terms: D000293:Adolescent; D000328:Adult; D000437:Alcoholism / Q000628:therapy; D001289:Attention Deficit Disorder with Hyperactivity / Q000628:therapy; D001321:Autistic Disorder / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D013223:Statistics as Topic; D016896:Treatment Outcome
keywords: adaptive intervention; longitudinal analysis; marginal structural model; sequential multiple assignment randomized trial