title: Longitudinal missing data strategies for substance use clinical trials using generalized estimating equations: an example with a buprenorphine trial.
abstract: OBJECTIVE
  A review of substance use clinical trials indicates that sub-optimal methods are the most commonly used procedures to deal with longitudinal missing information.
  
  
  METHODS
  Listwise deletion (i.e., using complete cases only), positive urine analysis (UA) imputation, and multiple imputation (MI) were used to evaluate the effect of baseline substance use and buprenorphine/naloxone tapering schedule (7 or 28 days) on the probability of a positive UA (UA+) across the 4-week treatment period.
  
  
  RESULTS
  The listwise deletion generalized estimating equations (GEE) model demonstrated that those in the 28-day taper group were less likely to submit a UA+ for opioids during the treatment period (odds ratios (OR) = 0.57, 95% confidence interval (CI): 0.39-0.83), as did the positive UA imputation model (OR = 0.43, CI: 0.34-0.55). The MI model also demonstrated a similar effect of taper group (OR = 0.57, CI: 0.42-0.77), but the effect size was more similar to that of the listwise deletion model.
  
  
  CONCLUSIONS
  Future researchers may find utilization of the MI procedure in conjunction with the common method of GEE analysis as a helpful analytic approach when the missing at random assumption is justifiable.
authors.affiliation: College of Nursing, Washington State University, Spokane, Washington, USA; Department of Psychology, Washington State University, Pullman, Washington, USA; Program of Excellence in the Addictions, Washington State University, Spokane, Washington, USA; Program for Rural Mental Health and Substance Abuse Treatment, Washington State University, Spokane, Washington, USA; Translational Addictions Research Center, Washington State University, Spokane, Washington, USA.
authors.forename: Sterling
authors.initials: S
authors.lastname: McPherson
authors.forename: Celestina
authors.initials: C
authors.lastname: Barbosa-Leiker
authors.forename: Michael
authors.initials: M
authors.lastname: McDonell
authors.forename: Donelle
authors.initials: D
authors.lastname: Howell
authors.forename: John
authors.initials: J
authors.lastname: Roll
mesh_terms: D002047:Buprenorphine / Q000009:adverse effects / Q000652:urine; D002986:Clinical Trials as Topic / Q000379:methods*; D003627:Data Interpretation, Statistical; D006801:Humans; D008137:Longitudinal Studies / Q000379:methods; D019966:Substance-Related Disorders / Q000175:diagnosis* / Q000453:epidemiology / Q000652:urine
chemical_list: D002047:Buprenorphine
keywords: generalized estimating equations; longitudinal missing data; multiple imputation; positive urine analysis imputation; psychopharmacology clinical trials; substance use disorder treatment