Lessons learned from prematurely terminated clinical trials.
Controlled clinical trials in cardiovascular disease are the cornerstone for therapeutic advances in this field of medicine. Since the introduction of the concept of controlled clinical trials, there has been substantial progress in the design, conduct, and analysis of such studies. A growing awareness of ethical issues emerging from such trials has led to increased public and investigator scrutiny, and the routine requirement for interim data analysis. A benefit of such interim analysis is that either an entire clinical trial or a specific treatment limb can be stopped if the observed findings warrant premature termination. For example, highly positive findings, as were noted in the Heart Outcomes Prevention Evaluation (HOPE) study, led to its closure about 1 year early after 4.5 years of treatment. Alternatively, the doxazosin treatment limb of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) and the amlodipine treatment limb of the African-American Study of Kidney Disease and Hypertension (AASK) were stopped early because of negative findings. Finally, economic considerations can enter into the decision to close a study early as was the case in the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) trial. Most such decisions rely heavily on information obtained from independent data and safety monitoring boards. Such boards ensure patient safety by providing an unbiased ongoing review of data, which would otherwise be unavailable until a study's completion. Early termination of a clinical trial can have important clinical implications and, in particular, can redirect patterns of clinical practice.
Sica
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Division of Nephrology, Medical College of Virginia of Virginia Commonwealth University, Box 980160, Richmond, VA 23298, USA. dsica@ hsc.vcu.edu
D002318:Cardiovascular Diseases / Q000188:drug therapy*; D018849:Controlled Clinical Trials as Topic; D006801:Humans; D013997:Time Factors