Challenges in conducting a pediatric longitudinal prevention study: Lessons from the ACE-inhibitor after anthracycline trial

Abstract

The ACE-inhibitor After Anthracyclines (AAA) trial was the first randomized, double-blind, placebo-controlled prevention study aimed at reducing the rate of a chemotherapy associated late side effects in pediatric oncology survivors. A prevention study in this population faced major obstacles to the successful completion of the trial. This report discusses the challenges investigators faced when specific aspects of the trial threatened its completion, including aspects of study design; methods of recruitment of patients; methods to determine pediatric dosing; techniques to increase drug compliance and retention of patients; study conduct; use of information systems to track results; analytic techniques; and investigator relationships with NIH institutes as well as the Data and Safety Monitoring Board (DSMB). The lessons learned from the AAA trial experience may aid in the improved structuring of future prevention trials utilizing a randomized, double-blind methodology in a population of survivors of pediatric cancer.