title: Instrumental variables and interactions in the causal analysis of a complex clinical trial.
abstract: We consider the application of instrumental variable techniques in a longitudinal clinical trial in paediatric HIV/AIDS, with a substantial degree of non-compliance to randomized treatment (Nelfinavir versus placebo) and with left censoring of the outcome variable (HIV RNA concentration). We consider in detail the assumptions and implications behind the inclusion and exclusion of interactions between randomized arm and baseline covariates in modelling actual treatment received, and between treatment and baseline covariates in modelling outcome. Estimated treatment effects were sensitive to inclusion of interactions, and we show how such sensitivity can be explored and explained.
authors.affiliation: Medical Research Council Biostatistics Unit, Institute of Public Health, University Forvie Site, Robinson Way, Cambridge, CB2 2SR, UK. simon.bond@mrc-bsu.cam.ac.uk
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Bond
authors.forename: Ian R
authors.initials: IR
authors.lastname: White
authors.forename: A
authors.initials: A
authors.lastname: Sarah Walker
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D002648:Child; D003627:Data Interpretation, Statistical; D005260:Female; D006678:HIV / Q000254:growth & development; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D015233:Models, Statistical; D019888:Nelfinavir / Q000627:therapeutic use; D010349:Patient Compliance; D012367:RNA, Viral / Q000097:blood; D016032:Randomized Controlled Trials as Topic / Q000379:methods*
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D019888:Nelfinavir