title: Addressing challenges of clinical trials in acute pain: The Pain Management of Vaso-occlusive Crisis in Children and Young Adults with Sickle Cell Disease Study.
abstract: Neuropathic pain is a known component of vaso-occlusive pain in sickle cell disease; however, drugs targeting neuropathic pain have not been studied in this population. Trials of acute pain are complicated by the need to obtain consent, to randomize participants expeditiously while optimally treating pain. We describe the challenges in designing and implementing the Pain Management of Vaso-occlusive Crisis in Children and Young Adults with Sickle Cell Disease Study (NCT01954927), a phase II, randomized, double-blind, placebo-controlled trial to determine the effect of gabapentin for vaso-occlusive crisis.
  
  
  
  In the Pain Management of Vaso-occlusive Crisis in Children and Young Adults with Sickle Cell Disease Study, we aim to assess the analgesic effect of gabapentin during vaso-occlusive crisis. Difficulties we identified included avoiding delay of notification of study staff of potential participants which we resolved by automated notification. Concern for rapid randomization and drug dispensation was addressed through careful planning with an investigational pharmacy and a single liquid formulation. We considered obtaining consent during well-visits to avoid the time constraints with acute presentations, but the large number of patients and limited duration that consent is valid made this impractical.
  
  
  
  In all, 79% of caregivers/children approached have agreed to participate. The trial is currently active, and enrollment is at 45.8% of that targeted (76 of 166) and expected to continue for two more years. Maintaining staff availability after-hours remains problematic, with 8% of screened patients missed for lack of available staff.
  
  
  
  Lessons learned in designing a trial to expedite procedures in the acute pain setting include (1) building study evaluations upon a standard-of-care backbone; (2) implementing a simple study design to facilitate consent and data capture; (3) assuring ample, well-trained study staff; and (4) utilizing technology to automate procedures whenever possible.
  
  
  
  This study design has circumvented many of the logistical barriers usually associated with acute pain trials and may serve as a prototype for future studies.
authors.affiliation: Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA kerri.nottage@stjude.org.
authors.forename: Kerri A
authors.initials: KA
authors.lastname: Nottage
authors.affiliation: Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Jane S
authors.initials: JS
authors.lastname: Hankins
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Lane G
authors.initials: LG
authors.lastname: Faughnan
authors.affiliation: Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Dustin M
authors.initials: DM
authors.lastname: James
authors.affiliation: Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Richardson
authors.affiliation: Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Robbin
authors.initials: R
authors.lastname: Christensen
authors.affiliation: Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Guolian
authors.initials: G
authors.lastname: Kang
authors.affiliation: Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Smeltzer
authors.affiliation: Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Cancio
authors.affiliation: Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Winfred C
authors.initials: WC
authors.lastname: Wang
authors.affiliation: Division of Anesthesiology, Department of Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Doralina L
authors.initials: DL
authors.lastname: Anghelescu
mesh_terms: D000208:Acute Disease; D059787:Acute Pain / Q000188:drug therapy*; D000293:Adolescent; D000328:Adult; D000588:Amines / Q000008:administration & dosage*; D000700:Analgesics / Q000008:administration & dosage*; D000755:Anemia, Sickle Cell / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D000077206:Gabapentin; D006801:Humans; D007223:Infant; D008297:Male; D059408:Pain Management / Q000379:methods*; D010147:Pain Measurement; D012107:Research Design; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage*
chemical_list: D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin
keywords: Vaso-occlusive crisis; gabapentin; neuropathic pain; sickle cell disease