Received December 18, 2007
Accepted on February 18, 2008

ORIGINAL ARTICLES

Lessons for Successful Study Enrollment from the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network Study

Susan T. Crowley ^*1, Glenn M. Chertow , Joseph Vitale , Theresa O’Connor , Jane Zhang , Roland M.H. Schein , Devasmita Choudhury ^||, Kevin Finkel ^¶, Anitha Vijayan ^**, Emil Paganini , Paul M. Palevsky , and for the VA/NIH Acute Renal Failure Trial Network Study Group

*Renal Section, Acute Care Service Line, Veterans Administration Connecticut Healthcare System, West Haven, and Nephrology Section, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut; Division of Nephrology, Departments of Medicine and Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California; Veterans Administration Cooperative Studies Program Coordinating Center, West Haven, Connecticut; Section of Critical Care Medicine, Veterans Administration Miami Medical Center, and Division of Pulmonary and Critical Care Medicine, University of Miami Miller School of Medicine, Miami, Florida; ||Renal Section, Medical Specialty Service Line, Veterans Administration North Texas Healthcare Center, and Renal Division, Department of Medicine, University of Texas Southwestern Medical School, Dallas, Texas; ¶Division of Renal Diseases and Hypertension, Department of Medicine, University of Texas Medical School, Houston, Texas; **Renal Division, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri; Dialysis and Extracorporeal Therapy, Department of Nephrology and Hypertension, Cleveland Clinic Foundation, Cleveland, Ohio; and Renal Section, Medical Specialty Service Line, Veterans Administration Pittsburgh Healthcare System, and Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

¹ To whom correspondence should be addressed. E-mail: susan.crowley{at}yale.edu.

	Abstract

Background and objectives: 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.

Design, setting, participants, & measurements: 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.