title: Time-varying SMART design and data analysis methods for evaluating adaptive intervention effects.
abstract: In a standard two-stage SMART design, the intermediate response to the first-stage intervention is measured at a fixed time point for all participants. Subsequently, responders and non-responders are re-randomized and the final outcome of interest is measured at the end of the study. To reduce the side effects and costs associated with first-stage interventions in a SMART design, we proposed a novel time-varying SMART design in which individuals are re-randomized to the second-stage interventions as soon as a pre-fixed intermediate response is observed. With this strategy, the duration of the first-stage intervention will vary.
  
  
  
  We developed a time-varying mixed effects model and a joint model that allows for modeling the outcomes of interest (intermediate and final) and the random durations of the first-stage interventions simultaneously. The joint model borrows strength from the survival sub-model in which the duration of the first-stage intervention (i.e., time to response to the first-stage intervention) is modeled. We performed a simulation study to evaluate the statistical properties of these models.
  
  
  
  Our simulation results showed that the two modeling approaches were both able to provide good estimations of the means of the final outcomes of all the embedded interventions in a SMART. However, the joint modeling approach was more accurate for estimating the coefficients of first-stage interventions and time of the intervention.
  
  
  
  We conclude that the joint modeling approach provides more accurate parameter estimates and a higher estimated coverage probability than the single time-varying mixed effects model, and we recommend the joint model for analyzing data generated from time-varying SMART designs. In addition, we showed that the proposed time-varying SMART design is cost-efficient and equally effective in selecting the optimal embedded adaptive intervention as the standard SMART design.
authors: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 1400 Pressler Dr, FCT4.6002, Houston, TX, 77030, USA.
authors: Tianjiao
authors: T
authors: Dai
authors: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 1400 Pressler Dr, FCT4.6002, Houston, TX, 77030, USA. sshete@mdanderson.org.|Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. sshete@mdanderson.org.
authors: Sanjay
authors: S
authors: Shete
mesh_terms: D000465:Algorithms; D001699:Biometry / Q000379:methods*; D006801:Humans; D008962:Models, Theoretical; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data*; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D015203:Reproducibility of Results; D012107:Research Design; D013997:Time Factors
keywords: Adaptive interventions; Joint model; Longitudinal model; Sequential multiple assignment randomized trial (SMART); Time-varying mixed effects model (TVMEM)