Pharmacotherapy in congestive heart failure. Prematurely terminated clinical trials and their application to cardiovascular medicine.
Controlled clinical trials in cardiovascular disease remain the cornerstone of field-specific therapeutic advances. Since the introduction of the concept of controlled clinical trials, there has been considerable fine-tuning of 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 both interim data analysis and full conflict-of-interest disclosure. A benefit of such interim analyses is that either an entire clinical trial or a specific treatment limb can be stopped if the observed findings warrant early termination. For example, highly positive findings, as were noted in the HOPE Study (Heart Outcomes Prevention Evaluation), led to its closure after 4.5 years of treatment, which was 1 year earlier than anticipated. Also, the doxazosin treatment limb of ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) and the amlodipine treatment limb of AASK (African American Study of Kidney Disease and Hypertension) were stopped early, because of negative findings in one of their treatment limbs. Finally, economic considerations can enter into the decision to close a study early, as was the case in the CONVINCE (Controlled-Onset Verapamil Investigation of Cardiovascular Endpoints) 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 and economic implications and, in particular, can substantially redirect the pattern of clinical practice. (c)2001 CHF, Inc.
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Section of Clinical Pharmacology and Hypertension, Division of Nephrology, Medical College of Virginia of Virginia Commonwealth University, Richmond, VA 23298.