title: Lessons for successful study enrollment from the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network Study.
abstract: OBJECTIVE
  Design elements of clinical trials can introduce recruitment bias and reduce study efficiency. Trials involving the critically ill may be particularly prone to design-related inefficiencies.
  
  
  METHODS
  Enrollment into the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network Study was systematically monitored. Reasons for nonenrollment into this study comparing strategies of renal replacement therapy in critically ill patients with acute kidney injury were categorized as modifiable or nonmodifiable.
  
  
  RESULTS
  4339 patients were screened; 2744 fulfilled inclusion criteria. Of these, 1034 were ineligible by exclusion criteria. Of the remaining 1710 patients, 1124 (65.7%) enrolled. Impediments to informed consent excluded 21.4% of potentially eligible patients. Delayed identification of potential patients, physician refusal, and involvement in competing trials accounted for 4.4, 2.7, and 2.3% of exclusions. Comfort measures only status, chronic illness, chronic kidney disease, and obesity excluded 11.8, 7.8, 7.6, and 5.9% of potential patients. Modification of an enrollment window reduced the loss of patients from 6.6 to 2.3%.
  
  
  CONCLUSIONS
  The Acute Renal Failure Trial Network Study's enrollment efficiency compared favorably with previous intensive care unit intervention trials and supports the representativeness of its enrolled population. Impediments to informed consent highlight the need for nontraditional acquisition methods. Restrictive enrollment windows may hamper recruitment but can be effectively modified. The low rate of physician refusal acknowledges clinical equipoise in the study design. Underlying comorbidities are important design considerations for future trials that involve the critically ill with acute kidney injury.
authors.affiliation: Renal Section (111F), VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT 06516, USA. susan.crowley@yale.edu
authors.forename: Susan T
authors.initials: ST
authors.lastname: Crowley
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Chertow
authors.forename: Joseph
authors.initials: J
authors.lastname: Vitale
authors.forename: Theresa
authors.initials: T
authors.lastname: O'Connor
authors.forename: Jane
authors.initials: J
authors.lastname: Zhang
authors.forename: Roland M H
authors.initials: RM
authors.lastname: Schein
authors.forename: Devasmita
authors.initials: D
authors.lastname: Choudhury
authors.forename: Kevin
authors.initials: K
authors.lastname: Finkel
authors.forename: Anitha
authors.initials: A
authors.lastname: Vijayan
authors.forename: Emil
authors.initials: E
authors.lastname: Paganini
authors.forename: Paul M
authors.initials: PM
authors.lastname: Palevsky
mesh_terms: D058186:Acute Kidney Injury / Q000401:mortality / Q000628:therapy*; D015982:Bias; D002986:Clinical Trials as Topic / Q000379:methods; D016638:Critical Illness; D017583:Hemodiafiltration; D006801:Humans; D007258:Informed Consent; D007362:Intensive Care Units; D015337:Multicenter Studies as Topic; D009316:National Institutes of Health (U.S.); D018579:Patient Selection; D016032:Randomized Controlled Trials as Topic; D006435:Renal Dialysis; D012107:Research Design; D016896:Treatment Outcome; D014481:United States; D014493:United States Department of Veterans Affairs