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
DOI:
https://doi.org/10.6000/1929-6029.2016.05.01.2Keywords:
Exposure-crossover design, self-matching, confounding, causal effects, generalized estimating equation.Abstract
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 each treatment episode of 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 the Induction (4.9) to the Subsequent (4.1) intervals, with the treatment episode falling 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 the Subsequent than the Induction intervals. 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.
References
Maclure M. The case-crossover design: a method for studying transient effects on the risk of acute events. Am J Epideiol 1991; 133(2): 144-53. DOI: https://doi.org/10.1093/oxfordjournals.aje.a115853
Rothman KJ. Greenland S. Modern epidemiology. 2nd ed. Philadelphia: Lippincott Williams & Wilkins 1998; 111-112, 137.
Redelmeier DA. The exposure-crossover design is a new method for studying sustained changes in recurrent events. J Clin Epidemiol 2013; 66: 955-63. http://dx.doi.org/10.1016/j.jclinepi.2013.05.003 DOI: https://doi.org/10.1016/j.jclinepi.2013.05.003
Redelmeier DA, Zung JD, Thiruchelvam D, Tibshirani RJ. Fibromyalgia and the risk of a subsequent motor vehicle crash. J Rheumatol 2015; 42: 7. doi:10.3899/jrheum. 141315. DOI: https://doi.org/10.3899/jrheum.141315
Schlenker MB, Thiruchelvam D, Redelmeier DA. Intravitreal anti–vascular endothelial growth factor treatment and the risk of thromboembolism. Am J Ophthalmol 2015; 160(3): 569-580. http://dx.doi.org/10.1016/j.ajo.2015.06.011 DOI: https://doi.org/10.1016/j.ajo.2015.06.011
Lonergan E, Britton AM, Luxenberg J. Antipsychotics for delirium. Cochrane Database of Systematic Reviews 2007; Issue 2. Art. No.: CD005594. http://dx.doi.org/10.1002/14651858.CD005594.pub2 DOI: https://doi.org/10.1002/14651858.CD005594.pub2
Pisani MA, Bramley K, Vest MT, Akgün KM, Araujo AL, Murphy TE. Association of cumulative dose of haloperidol with next-day delirium in older medical ICU patients. Crit Care Med 2015; 43(5): 996-1002. http://dx.doi.org/10.1097/CCM.0000000000000863 DOI: https://doi.org/10.1097/CCM.0000000000000863
Goodman and Gilman’s the pharmacological basis of therapeutics. 8th ed. New York: Pergamon Press 1990; 3-32.
Rubins DB. For objective causal inference, design trumps analysis. Ann Appl Statistics 2008; 2(3): 808-840. http://dx.doi.org/10.1214/08-AOAS187 DOI: https://doi.org/10.1214/08-AOAS187
Pisani MA, Murphy TE, Van Ness PH, et al. Characteristics associated with delirium in older patients in a medical intensive care unit. Arch Intern Med 2007; 167: 1629-1634. http://dx.doi.org/10.1001/archinte.167.15.1629 DOI: https://doi.org/10.1001/archinte.167.15.1629
Ely EW, Margolin R, Francis J, et al. Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Crit Care Med 2001; 29(7): 1370-1379. http://dx.doi.org/10.1097/00003246-200107000-00012 DOI: https://doi.org/10.1097/00003246-200107000-00012
Inouye SK, Kosar CM, Tommet D, et al. The CAM-S: Development and validation of a new scoring system for delirium severity in 2 cohorts. Ann Intern Med 2014; 160: 526-533. http://dx.doi.org/10.7326/M13-1927 DOI: https://doi.org/10.7326/M13-1927
Han L, McCusker J, Cole M, Abrahamowicz M, Primeau F, Elie M. Use of medications with anticholinergic effect predicts clinical severity of delirium symptoms in older medical inpatients Arch Intern Med 2001; 161: 1099-105. http://dx.doi.org/10.1001/archinte.161.8.1099 DOI: https://doi.org/10.1001/archinte.161.8.1099
Durán CE, Azermai M, Vander Stichele RH. Systematic review of anticholinergic risk scales in older adults. Eur J Clin Pharmacol 2013; 69(7): 1485-96. http://dx.doi.org/10.1007/s00228-013-1499-3 DOI: https://doi.org/10.1007/s00228-013-1499-3
McCulloch CE, Searle SR. Generalized, linear and mixed models. New York: John Wiley & Sons 2001. DOI: https://doi.org/10.1002/9780470057339.vag009
Maclure M, Mittleman MA. Should we use a case-crossover design? Annu Rev Public Health 2000; 21: 193-221. http://dx.doi.org/10.1146/annurev.publhealth.21.1.193 DOI: https://doi.org/10.1146/annurev.publhealth.21.1.193
Stukel TA, Fisher ES, Wennberg DE, Alter DA, Gottlieb DJ, Vermeulen MJ. Analysis of observational studies in the presence of treatment selection bias. JAMA 2007; 297: 278-285. http://dx.doi.org/10.1001/jama.297.3.278 DOI: https://doi.org/10.1001/jama.297.3.278
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2016 Ling Han, M. A. Pisani, K.L. B. Araujo, Heather G. Allore
This work is licensed under a Creative Commons Attribution 4.0 International License.
Policy for Journals/Articles with Open Access
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are permitted and encouraged to post links to their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work
Policy for Journals / Manuscript with Paid Access
Authors who publish with this journal agree to the following terms:
- Publisher retain copyright .
- Authors are permitted and encouraged to post links to their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work .
