Lessons for successful study enrollment from the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network Study.
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.
Crowley
Susan T
ST
Renal Section (111F), VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT 06516, USA. susan.crowley@yale.edu
Chertow
Glenn M
GM
Vitale
Joseph
J
O'Connor
Theresa
T
Zhang
Jane
J
Schein
Roland M H
RM
Choudhury
Devasmita
D
Finkel
Kevin
K
Vijayan
Anitha
A
Paganini
Emil
E
Palevsky
Paul M
PM
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