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. The VA/NIH Acute Renal Failure Trial Network (ATN) Study was designed to compare strategies of renal replacement therapy (RRT) in critically ill subjects with acute kidney injury (AKI).
Reasons for subject non-enrollment into the ATN Study were systematically monitored and categorized as modifiable or non-modifiable.
4339 subjects were screened; 2744 fulfilled inclusion criteria. Of these, 1034 were ineligible based on exclusion criteria. Of the remaining 1710 patients, 1124 (65.7%) enrolled. Impediments to informed consent excluded 21.4% of potentially eligible subjects; surrogate unavailability accounted for 1/3 of these exclusions. Delayed identification of potential subjects, physician refusal, and involvement in competing trials accounted for 4.4%, 2.7%, and 2.3% of exclusions. Comfort measures only (CMO) status, chronic illness, chronic kidney disease (CKD), and obesity excluded 11.8%, 7.8%, 7.6%, and 5.9% of potential subjects. Modification of an enrollment window reduced the loss of subjects from 6.6% to 2.3%.
The ATN Study’s enrollment efficiency compared favorably with previous ICU intervention trials and supports the representativeness of its enrolled population. Impediments to informed consent in the critically ill with AKI highlight the need for nontraditional acquisition methods. Restrictive enrollment windows may hamper subject 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 involving the critically ill with AKI.
Mesh terms: Acute Kidney Injury, Clinical Trial, Research Design, Recruitment, Enrollment, Critical Care, External Validity