Data Monitoring in the Randomized Evaluation of Strategies for Left Ventricular Dysfunction Pilot Study: When Reasonable People Disagree

Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) was a pilot study to examine the effects of various doses of an angiotensin II receptor blocker (ARB) candesartan; an angiotensinconverting enzyme inhibitor (ACE-I) enalapril; and their combination on a number of surrogate outcomes (exercise tolerance, LV function, neurohormones) in patients with congestive heart failure (CHF). A subset of patients was also randomized a second time at four months after the initial randomization to receive a beta-blocker, metoprolol CR, or placebo utilizing a partial factorial design. This pilot study was used to identify a dose of candesartan to be used in a large-scale study evaluating clinical outcomes. Toward the end of the study the External Safety and Efficacy Monitoring Committee (ESEMC) recommended that the trial be terminated. The Steering Committee (SC) disagreed with this decision and requested an external expert panel to provide further input, which led to terminating the study about four weeks prior to its scheduled end. Lessons learned by the Coordinating Center and SC are presented.