A structural mean model to allow for noncompliance in a randomized trial comparing 2 active treatments.
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.
Fischer
Krista
K
MRC Biostatistics Unit, Institute of Public Health, University Forvie Site, Robinson Way, Cambridge, UK. krista.fischer@ut.ee
Goetghebeur
Els
E
Vrijens
Bernard
B
White
Ian R
IR
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
D005473:Fluoxetine; D017374:Paroxetine
J Antimicrob Chemother. 2005 May;55(5):616-27
15772145
Stat Med. 1997 May 15;16(9):1017-29
9160496
BMJ. 1996 Jul 6;313(7048):36-9
8664772
J Clin Pharmacol. 2005 Apr;45(4):461-7
15778427
Stat Methods Med Res. 2005 Aug;14(4):327-47
16178136
Int Clin Psychopharmacol. 2008 Jan;23(1):36-42
18090506
Acta Psychiatr Scand. 2004 Sep;110(3):201-7
15283740
Stat Methods Med Res. 2011 Jun;20(3):191-215
19036909
Br J Psychiatry. 2003 Oct;183:323-31
14519610
Biol Psychiatry. 1998 Jul 15;44(2):77-87
9646889
Stat Med. 1991 Jan;10(1):45-52
2006355
Ann Intern Med. 2000 Sep 19;133(6):464-70
10975965
Stat Med. 1998 Feb 15;17(3):269-302; discussion 387-9
9493255
J Health Econ. 2003 Mar;22(2):151-85
12606142
Biostatistics. 2008 Apr;9(2):277-89
17681993