title: A trial of in-hospital, electronic alerts for acute kidney injury: design and rationale.
abstract: BACKGROUND
  Acute kidney injury is common in hospitalized patients, increases morbidity and mortality, and is under-recognized. To improve provider recognition, we previously developed an electronic alert system for acute kidney injury. To test the hypothesis that this electronic acute kidney injury alert could improve patient outcome, we designed a randomized controlled trial to test the effectiveness of this alert in hospitalized patients. The study design presented several methodologic, ethical, and statistical challenges.
  
  
  OBJECTIVE
  To highlight the challenges faced and the solutions employed in the design and implementation of a clinical trial to determine whether the provision of an early electronic alert for acute kidney injury would improve outcomes in hospitalized patients. Challenges included how to randomize the delivery of the alert system and the ethical framework for waiving informed consent. Other methodologic challenges included the selection and statistical evaluation of our study outcome, a ranked-composite of a continuous covariate (creatinine) and two dichotomous outcomes (dialysis and death), and the use of the medical record as a source of trial data.
  
  
  METHODS
  We have designed a randomized trial to assess the effectiveness of an electronic alert system for acute kidney injury. With broad inclusion criteria, and a waiver of informed consent, we enroll and randomize virtually every patient with acute kidney injury in our hospital.
  
  
  RESULTS
  As of 31 March 2014, we have enrolled 2373 patients of 2400 targeted. Pre-alert data demonstrated a strong association between severity of acute kidney injury and inpatient mortality with a range of 6.4% in those with mild, stage 1 acute kidney injury, to 29% among those with stage 3 acute kidney injury (p < 0.001). We judged that informed consent would undermine the scientific validity of the study and present harms that are out of proportion to the very low risk intervention.
  
  
  CONCLUSIONS
  Our study demonstrates the feasibility of designing an ethical randomized controlled trial of an early electronic alert for acute kidney injury without obtaining informed consent from individual participants. Our study outcome may serve as a model for other studies of acute kidney injury, insofar as our paradigm accounts for the effect that early death and dialysis have on assessment of acute kidney injury severity as defined by maximum achieved serum creatinine.
authors.affiliation: Renal, Electrolyte and Hypertension Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA francisw@mail.med.upenn.edu.
authors.forename: Francis Perry
authors.initials: FP
authors.lastname: Wilson
authors.affiliation: Renal, Electrolyte and Hypertension Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Reese
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA Pulmonary, Allergy and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Michael Gs
authors.initials: MG
authors.lastname: Shashaty
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Susan S
authors.initials: SS
authors.lastname: Ellenberg
authors.affiliation: Renal, Electrolyte and Hypertension Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Yevgeniy
authors.initials: Y
authors.lastname: Gitelman
authors.affiliation: Renal, Electrolyte and Hypertension Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Amar D
authors.initials: AD
authors.lastname: Bansal
authors.affiliation: Department of Information Services, University of Pennsylvania, Philadelphia PA, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Urbani
authors.affiliation: Renal, Electrolyte and Hypertension Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Harold I
authors.initials: HI
authors.lastname: Feldman
authors.affiliation: Pulmonary, Allergy and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Barry
authors.initials: B
authors.lastname: Fuchs
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000175:diagnosis*; D003404:Creatinine / Q000097:blood*; D004311:Double-Blind Method; D001330:Electronic Data Processing; D057286:Electronic Health Records; D006760:Hospitalization; D006801:Humans; D017063:Outcome Assessment, Health Care
chemical_list: D003404:Creatinine
keywords: Acute kidney injury; acute renal failure; composite outcomes; ethics; waiver of informed consent