title: Application of the Gradient Boosted method in randomised clinical trials: Participant variables that contribute to depression treatment efficacy of duloxetine, SSRIs or placebo.
abstract: BACKGROUND
  Randomised, placebo-controlled trials of treatments for depression typically collect outcomes data but traditionally only analyse data to demonstrate efficacy and safety. Additional post-hoc statistical techniques may reveal important insights about treatment variables useful when considering inter-individual differences amongst depressed patients. This paper aims to examine the Gradient Boosted Model (GBM), a statistical technique that uses regression tree analyses and can be applied to clinical trial data to identify and measure variables that may influence treatment outcomes.
  
  
  METHODS
  GBM was applied to pooled data from 12 randomised clinical trials of 4987 participants experiencing an acute depressive episode who were treated with duloxetine, an SSRI or placebo to predict treatment remission. Additional analyses were conducted on the same dataset using the logistic regression model for comparison between these two methods.
  
  
  RESULTS
  With GBM, there were noticeable differences between treatments when identifying which and to what extent variables were associated with remission. A single logistic regression only revealed a decreasing or increasing relationship between predictors and remission while GBM was able to reveal a complex relationship between predictors and remission.
  
  
  CONCLUSIONS
  These analyses were conducted post-hoc utilising clinical trials databases. The criteria for constructing the analyses data were based on the characteristics of the clinical trials.
  
  
  CONCLUSIONS
  GBM can be used to identify and quantify patient variables that predict remission with specific treatments and has greater flexibility than the logistic regression model. GBM may provide new insights into inter-individual differences in treatment response that may be useful for selecting individualised treatments.
  
  
  BACKGROUND
  IMPACT clinical trial number 3327; IMPACT clinical trial number 4091; IMPACT clinical trial number 4689; IMPACT clinical trial number 4298; NCT00071695; NCT00062673; NCT00036335; NCT00067912; NCT00073411; NCT00489775; NCT00536471; NCT00666757 (note that trials with IMPACT numbers predate mandatory clinical trial registration requirements).
authors: Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia; IMPACT SRC (Innovation in Mental and Physical Health and Clinical Treatment), School of Medicine, Deakin University, Geelong, VIC, Australia. Electronic address: seetald@barwonhealth.org.au.
authors: Seetal
authors: S
authors: Dodd
authors: Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia; IMPACT SRC (Innovation in Mental and Physical Health and Clinical Treatment), School of Medicine, Deakin University, Geelong, VIC, Australia; Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia; ORYGEN Research Centre, Parkville, VIC, Australia.
authors: Michael
authors: M
authors: Berk
authors: Eli Lilly Australia Pty Limited, West Ryde, NSW, Australia.
authors: Katarina
authors: K
authors: Kelin
authors: Eli Lilly and Company, Indianapolis, IN, USA.
authors: Qianyi
authors: Q
authors: Zhang
authors: Department of Pharmacology and the Institute of Physiology and Neuroscience, Sahlgrenska, Academy, Goteborg University, Goteborg, Sweden.
authors: Elias
authors: E
authors: Eriksson
authors: Eli Lilly and Company, Brussels, Belgium.
authors: Walter
authors: W
authors: Deberdt
authors: University of California, San Francisco, CA, USA.
authors: J
authors: J
authors: Craig Nelson
mesh_terms: D000328:Adult; D000368:Aged; D003863:Depression / Q000188:drug therapy*; D003866:Depressive Disorder / Q000188:drug therapy*; D000068736:Duloxetine Hydrochloride; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D013876:Thiophenes / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000068736:Duloxetine Hydrochloride; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes
keywords: Depression; Duloxetine; Gradient Boosted method; Randomised clinical trial; SSRI