Use of Self-Matching to Control for Stable Patient Characteristics While Addressing Time-Varying Confounding on Treatment Effect: A Case Study of Older Intensive Care Patients.
Exposure-crossover design offers a non-experimental option to control for stable baseline confounding through self-matching while examining causal effect of an exposure on an acute outcome. This study extends this approach to longitudinal data with repeated measures of exposure and outcome using data from a cohort of 340 older medical patients in an intensive care unit (ICU). The analytic sample included 92 patients who received ≥1 dose of haloperidol, an antipsychotic medication often used for patients with delirium. Exposure-crossover design was implemented by sampling the 3-day time segments prior (Induction)and posterior (Subsequent)to eachtreatment episodeof receiving haloperidol. In the full cohort, there was a trend of increasing delirium severity scores (Mean±SD: 4.4±1.7) over the course of the ICU stay. After exposure-crossover sampling, the delirium severity score decreased from theInduction(4.9) to theSubsequent(4.1) intervals, with thetreatment episodefalling in-between (4.5). Based on a GEE Poisson model accounting for self-matching and within-subject correlation, the unadjusted mean delirium severity scores was -0.55 (95% CI: -1.10, -0.01) points lower for theSubsequentthan theInductionintervals. The association diminished by 32% (-0.38, 95%CI: -0.99, 0.24) after adjusting only for ICU confounding, while being slightly increased by 7% (-0.60, 95%CI: -1.15, -0.04) when adjusting only for baseline characteristics. These results suggest that longitudinal exposure-crossover design is feasible and capable of partially removing stable baseline confounding through self-matching. Loss of power due to eliminating treatment-irrelevant person-time and uncertainty around allocating person-time to comparison intervals remain methodological challenges.
Department of Internal Medicine, Program on Aging, Yale School of Medicine, New Haven, CT, USA.
Ling
L
Han
Department of Internal Medicine, Program on Aging, Yale School of Medicine, New Haven, CT, USA; Department of Internal Medicine, Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.
M A
MA
Pisani
Department of Internal Medicine, Program on Aging, Yale School of Medicine, New Haven, CT, USA.
K L B
KL
Araujo
Department of Internal Medicine, Program on Aging, Yale School of Medicine, New Haven, CT, USA; Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA.
Heather G
HG
Allore
Exposure-crossover design; causal effects; confounding; generalized estimating equation; self-matching