title: Local control for identifying subgroups of interest in observational research: persistence of treatment for major depressive disorder.
abstract: Caregivers are regularly faced with decisions between competing treatments. Large observational health care databases provide a golden opportunity for research on heterogeneity in patient response to guide caregiver decisions, due to their sample size, diverse populations, and real-world setting. Local control is a promising tool for using observational data to detect patient subgroups with differential response on one treatment relative to another. While standard data mining approaches find subgroups with optimal responses for a particular population, detecting subgroups that reveal treatment differences while also adjusting for confounding in observational data is challenging. Local control utilizes unsupervised clustering to form non-parametric patient-level counterfactual treatment differences and displays them as an observed distribution of effect-size estimates. Classification and regression trees (CART) then find the factors that drive the greatest outcome differentiation between treatments. In this manuscript, we demonstrate the use of this two-step strategy using local control plus CART to identify depression patients most (least) likely to benefit from treatment with duloxetine relative to extended-release venlafaxine. Prior medication costs and age were found to be factors most associated with differential outcome, with prior medication costs remaining as an important factor after sensitivity analyses using a second dataset.
authors: Eli Lilly and Company, Indianapolis, IN, USA.
authors: Douglas E
authors: DE
authors: Faries
authors: Yi
authors: Y
authors: Chen
authors: Ilya
authors: I
authors: Lipkovich
authors: Anthony
authors: A
authors: Zagar
authors: Xianchen
authors: X
authors: Liu
authors: Robert L
authors: RL
authors: Obenchain
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D017028:Caregivers / Q000193:education / Q000523:psychology; D016000:Cluster Analysis; D003511:Cyclohexanols / Q000191:economics / Q000627:therapeutic use*; D057225:Data Mining; D003657:Decision Making; D003692:Delayed-Action Preparations; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000191:economics; D016527:Drug Costs / Q000706:statistics & numerical data; D000068736:Duloxetine Hydrochloride; D005260:Female; D006266:Health Education; D006801:Humans; D007344:Insurance Claim Reporting / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D064887:Observational Studies as Topic / Q000706:statistics & numerical data*; D010043:Outcome and Process Assessment, Health Care / Q000706:statistics & numerical data*; D013223:Statistics as Topic; D018709:Statistics, Nonparametric; D013876:Thiophenes / Q000191:economics / Q000627:therapeutic use*; D000069470:Venlafaxine Hydrochloride; D055815:Young Adult
chemical_list: D003511:Cyclohexanols; D003692:Delayed-Action Preparations; D013876:Thiophenes; D000069470:Venlafaxine Hydrochloride; D000068736:Duloxetine Hydrochloride
keywords: classification trees; cluster analysis; counterfactual; patient heterogeneity
references: Value Health. 2003 Mar-Apr;6(2):90-7
references: 12641858
references: Am J Public Health. 2004 Mar;94(3):361-6
references: 14998794
references: Clinicoecon Outcomes Res. 2011;3:63-72
references: 21935334
references: Value Health. 2009 Nov-Dec;12(8):1053-61
references: 19744292
references: Stat Med. 2011 Oct 30;30(24):2867-80
references: 21815180
references: Value Health. 2008 Jan-Feb;11(1):44-7
references: 18237359
references: BMC Psychiatry. 2005 Jan 04;5:1
references: 15631624
references: Stat Med. 2011 Sep 20;30(21):2601-21
references: 21786278
references: Value Health. 2009 Nov-Dec;12(8):1044-52
references: 19793072
references: Stat Med. 1998 Oct 15;17(19):2265-81
references: 9802183
references: Gen Hosp Psychiatry. 2009 May-Jun;31(3):206-19
references: 19410099
references: J Epidemiol Community Health. 2004 Apr;58(4):265-71
references: 15026432
references: J Med Econ. 2012;15(1):134-44
references: 22014076
references: N Engl J Med. 2000 Jun 22;342(25):1878-86
references: 10861324
references: BMC Psychiatry. 2011 Jan 31;11:19
references: 21281479
references: N Engl J Med. 2000 Jun 22;342(25):1887-92
references: 10861325
references: Med Care. 2007 Oct;45(10 Supl 2):S58-65
references: 17909385
references: PLoS Med. 2008 Mar 11;5(3):e67
references: 18336067
references: Prim Care Companion J Clin Psychiatry. 2001 Dec;3(6):232-235
references: 15014590
references: Med Care. 2006 Apr;44(4):300-3
references: 16565629
references: Value Health. 2009 Nov-Dec;12(8):1062-73
references: 19793071
references: J Psychiatr Res. 2008 Jan;42(1):22-34
references: 17445831
references: Clin Trials. 2010 Oct;7(5):574-83
references: 20667935
references: JAMA. 2009 Dec 16;302(23):2580-6
references: 20009058
references: PLoS Med. 2007 Oct 16;4(10):e297
references: 17941715
references: Prim Care Companion J Clin Psychiatry. 2007;9(4):271-9
references: 17934551