title: A structural mean model to allow for noncompliance in a randomized trial comparing 2 active treatments.
abstract: We propose a structural mean modeling approach to obtain compliance-adjusted estimates for treatment effects in a randomized-controlled trial comparing 2 active treatments. The model relates an individual's observed outcome to his or her counterfactual untreated outcome through the observed receipt of active treatments. Our proposed estimation procedure exploits baseline covariates that predict compliance levels on each arm. We give a closed-form estimator which allows for differential and unexplained selectivity (i.e. noncausal compliance-outcome association due to unobserved confounding) as well as a nonparametric error distribution. In a simple linear model for a 2-arm trial, we show that the distinct causal parameters are identified unless covariate-specific expected compliance levels are proportional on both treatment arms. In the latter case, only a linear contrast between the 2 treatment effects is estimable and may well be of key interest. We demonstrate the method in a clinical trial comparing 2 antidepressants.
authors.affiliation: MRC Biostatistics Unit, Institute of Public Health, University Forvie Site, Robinson Way, Cambridge, UK. krista.fischer@ut.ee
authors.forename: Krista
authors.initials: K
authors.lastname: Fischer
authors.forename: Els
authors.initials: E
authors.lastname: Goetghebeur
authors.forename: Bernard
authors.initials: B
authors.lastname: Vrijens
authors.forename: Ian R
authors.initials: IR
authors.lastname: White
mesh_terms: D000465:Algorithms; D015982:Bias; D003198:Computer Simulation; D003865:Major Depressive Disorder / Q000188:drug therapy; D004311:Double-Blind Method; D005473:Fluoxetine / Q000627:therapeutic use; D006801:Humans; D016014:Linear Models; D015233:Models, Statistical; D015337:Multicenter Studies as Topic / Q000379:methods; D017374:Paroxetine / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D016896:Treatment Outcome; D016903:Drug Monitoring
chemical_list: D005473:Fluoxetine; D017374:Paroxetine
references.citation: J Antimicrob Chemother. 2005 May;55(5):616-27
references.pmid: 15772145
references.citation: Stat Med. 1997 May 15;16(9):1017-29
references.pmid: 9160496
references.citation: BMJ. 1996 Jul 6;313(7048):36-9
references.pmid: 8664772
references.citation: J Clin Pharmacol. 2005 Apr;45(4):461-7
references.pmid: 15778427
references.citation: Stat Methods Med Res. 2005 Aug;14(4):327-47
references.pmid: 16178136
references.citation: Int Clin Psychopharmacol. 2008 Jan;23(1):36-42
references.pmid: 18090506
references.citation: Acta Psychiatr Scand. 2004 Sep;110(3):201-7
references.pmid: 15283740
references.citation: Stat Methods Med Res. 2011 Jun;20(3):191-215
references.pmid: 19036909
references.citation: Br J Psychiatry. 2003 Oct;183:323-31
references.pmid: 14519610
references.citation: Biol Psychiatry. 1998 Jul 15;44(2):77-87
references.pmid: 9646889
references.citation: Stat Med. 1991 Jan;10(1):45-52
references.pmid: 2006355
references.citation: Ann Intern Med. 2000 Sep 19;133(6):464-70
references.pmid: 10975965
references.citation: Stat Med. 1998 Feb 15;17(3):269-302; discussion 387-9
references.pmid: 9493255
references.citation: J Health Econ. 2003 Mar;22(2):151-85
references.pmid: 12606142
references.citation: Biostatistics. 2008 Apr;9(2):277-89
references.pmid: 17681993