title: A latent variable approach in simultaneous modeling of longitudinal and dropout data in schizophrenia trials.
abstract: Dropouts impact clinical trial outcome analyses. Ignoring missing data is not an acceptable option when planning, conducting or interpreting the analysis of a clinical trial. Treatment related efficacy and safety data observed in the trial may not always be sufficient in explaining the dropouts' mechanism. Nevertheless, these dropout data may carry important treatment-related information and present as an outcome by itself. Traditional analyses involve the use of the time-to-event approach assuming that the dropouts' hazard is solely related to the efficacy or safety profiles observed in a study. A latent variable approach was developed to generalize this approach and to implement a more flexible dropout hazard function in a schizophrenia trial. This unobserved latent variable was used to jointly model the longitudinal efficacy data and dropout profiles across treatments. The analysis provides a framework to model informative dropouts simultaneously with primary efficacy outcomes and make intelligent decisions in drug development.
authors.affiliation: Clinical Pharmacology Modeling and Simulation, GlaxoSmithKline, King of Prussia, PA, USA.
authors.forename: Navin
authors.initials: N
authors.lastname: Goyal
authors.forename: Roberto
authors.initials: R
authors.lastname: Gomeni
mesh_terms: D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008137:Longitudinal Studies; D000077152:Olanzapine; D010352:Patient Dropouts / Q000706:statistics & numerical data*; D016016:Proportional Hazards Models; D012559:Schizophrenia / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D000077152:Olanzapine
keywords: Clinical Trial Simulation; Dropout analysis; Latent Variable; NONMEM; PANSS; Schizophrenia