title: Design considerations for point-of-care clinical trials comparing methadone and buprenorphine treatment for opioid dependence in pregnancy and for neonatal abstinence syndrome.
abstract: BACKGROUND
  In recent years, the U.S. has experienced a significant increase in the prevalence of pregnant opioid-dependent women and of neonatal abstinence syndrome (NAS), which is caused by withdrawal from in-utero drug exposure. While methadone-maintenance currently is the standard of care for opioid dependence during pregnancy, research suggests that buprenorphine-maintenance may be associated with shorter infant hospital lengths of stay (LOS) relative to methadone-maintenance. There is no "gold standard" treatment for NAS but there is evidence that buprenorphine, relative to morphine or methadone, treatment may reduce LOS and length of treatment.
  
  
  METHODS
  Point-of-care clinical trial (POCCT) designs, maximizing external validity while reducing cost and complexity associated with classic randomized clinical trials, were selected for two planned trials to compare methadone to buprenorphine treatment for opioid dependence during pregnancy and for NAS. This paper describes design considerations for the Medication-assisted treatment for Opioid-dependent expecting Mothers (MOMs; estimated N = 370) and Investigation of Narcotics for Ameliorating Neonatal abstinence syndrome on Time in hospital (INFANTs; estimated N = 284) POCCTs, both of which are randomized, intent-to-treat, two-group trials. Outcomes would be obtained from participants' electronic health record at three participating hospitals. Additionally, a subset of infants in the INFANTs POCCT would be from mothers in the MOMs POCCT and, thus, potential interaction between medication treatment of mother and infant could be evaluated.
  
  
  CONCLUSIONS
  This pair of planned POCCTs would evaluate the comparative effectiveness of treatments for opioid dependence during pregnancy and for NAS. The results could have a significant impact on practice.
authors.affiliation: Addiction Sciences Division, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, 3131 Harvey Avenue, Cincinnati, OH 45229, USA. Electronic address: winhusen@carc.uc.edu.
authors.forename: Theresa
authors.initials: T
authors.lastname: Winhusen
authors.affiliation: Addiction Sciences Division, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, 3131 Harvey Avenue, Cincinnati, OH 45229, USA; Cincinnati Veterans Affairs Medical Center, 3200 Vine Street, Cincinnati, OH 45220, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Wilder
authors.affiliation: Perinatal Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, 3235 Eden Avenue, Cincinnati, OH 45267-0555, USA.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Wexelblatt
authors.affiliation: Addiction Sciences Division, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, 3131 Harvey Avenue, Cincinnati, OH 45229, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Theobald
authors.affiliation: Perinatal Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Hall
authors.affiliation: Addiction Sciences Division, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, 3131 Harvey Avenue, Cincinnati, OH 45229, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lewis
authors.affiliation: Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, PO Box 670526, Cincinnati, OH 45267-0526, USA.
authors.forename: James
authors.initials: J
authors.lastname: Van Hook
authors.affiliation: Department of Obstetrics and Gynecology, Good Samaritan Hospital, 375 Dixmyth Ave, Cincinnati, OH 45220, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Marcotte
mesh_terms: D000328:Adult; D001724:Birth Weight; D002047:Buprenorphine / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007902:Length of Stay; D008691:Methadone / Q000627:therapeutic use*; D009357:Neonatal Abstinence Syndrome / Q000188:drug therapy*; D058850:Opiate Substitution Treatment / Q000379:methods*; D009293:Opioid-Related Disorders / Q000188:drug therapy*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy; D012107:Research Design
chemical_list: D002047:Buprenorphine; D008691:Methadone
keywords: Buprenorphine; Methadone; NAS; Opioid; Point-of-care; Pregnancy