title: A point-of-care clinical trial comparing insulin administered using a sliding scale versus a weight-based regimen.
abstract: BACKGROUND
  Clinical trials are widely considered the gold standard in comparative effectiveness research (CER) but the high cost and complexity of traditional trials and concerns about generalizability to broad patient populations and general clinical practice limit their appeal. Unsuccessful implementation of CER results limits the value of even the highest quality trials. Planning for a trial comparing two standard strategies of insulin administration for hospitalized patients led us to develop a new method for a clinical trial designed to be embedded directly into the clinical care setting thereby lowering the cost, increasing the pragmatic nature of the overall trial, strengthening implementation, and creating an integrated environment of research-based care.
  
  
  OBJECTIVE
  We describe a novel randomized clinical trial that uses the informatics and statistics infrastructure of the Veterans Affairs Healthcare System (VA) to illustrate one key component (called the point-of-care clinical trial - POC-CT) of a 'learning healthcare system,' and settles a clinical question of interest to the VA.
  
  
  METHODS
  This study is an open-label, randomized trial comparing sliding scale regular insulin to a weight-based regimen for control of hyperglycemia, using the primary outcome length of stay, in non-ICU inpatients within the northeast region of the VA. All non-ICU patients who require in-hospital insulin therapy are eligible for the trial, and the VA's automated systems will be used to assess eligibility and present the possibility of randomization to the clinician at the point of care. Clinicians will indicate their approval for informed consent to be obtained by study staff. Adaptive randomization will assign up to 3000 patients, preferentially to the currently 'winning' strategy, and all care will proceed according to usual practices. Based on a Bayesian stopping rule, the study has acceptable frequentist operating characteristics (Type I error 6%, power 86%) against a 12% reduction of median length of stay from 5 to 4.4 days. The adaptive stopping rule promotes implementation of a successful treatment strategy.
  
  
  CONCLUSIONS
  Despite clinical equipoise, individual healthcare providers may have strong treatment preferences that jeopardize the success and implementation of the trial design, leading to low rates of randomization. Unblinded treatment assignment may bias results. In addition, generalization of clinical results to other healthcare systems may be limited by differences in patient population. Generalizability of the POC-CT method depends on the level of informatics and statistics infrastructure available to a healthcare system.
  
  
  CONCLUSIONS
  The methods proposed will demonstrate outcome-based evaluation of control of hyperglycemia in hospitalized veterans. By institutionalizing a process of statistically sound and efficient learning, and by integrating that learning with automatic implementation of best practice, the participating VA Healthcare Systems will accelerate improvements in the effectiveness of care.
authors.affiliation: Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Cooperative Studies Program, VA Boston Healthcare System, Boston, MA, USA. louis.fiore@va.gov
authors.forename: Louis D
authors.initials: LD
authors.lastname: Fiore
authors.forename: Mary
authors.initials: M
authors.lastname: Brophy
authors.forename: Ryan E
authors.initials: RE
authors.lastname: Ferguson
authors.forename: Leonard
authors.initials: L
authors.lastname: D'Avolio
authors.forename: John A
authors.initials: JA
authors.lastname: Hermos
authors.forename: Robert A
authors.initials: RA
authors.lastname: Lew
authors.forename: Gheorghe
authors.initials: G
authors.lastname: Doros
authors.forename: Chester H
authors.initials: CH
authors.lastname: Conrad
authors.forename: Joseph A Gus
authors.initials: JA
authors.lastname: O'Neil
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Sabin
authors.forename: James
authors.initials: J
authors.lastname: Kaufman
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Swartz
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Lawler
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Liang
authors.forename: J Michael
authors.initials: JM
authors.lastname: Gaziano
authors.forename: Philip W
authors.initials: PW
authors.lastname: Lavori
mesh_terms: D001835:Body Weight; D057186:Comparative Effectiveness Research; D004305:Dose-Response Relationship, Drug; D057286:Electronic Health Records; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy*; D007328:Insulin / Q000008:administration & dosage* / Q000627:therapeutic use; D007902:Length of Stay; D050316:Medical Order Entry Systems; D019095:Point-of-Care Systems; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design
chemical_list: D007328:Insulin