Premature termination of clinical trials--lessons learned.
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 heightened public awareness, increased investigator scrutiny, and reinforced the need for interim data analysis. 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 argue for premature termination. For example, highly positive findings, as were noted in the HOPE Study (Heart Outcomes Prevention Evaluation), led to its being stopped after 4.5 years of treatment, which was 1 year early. Alternatively, the doxazosin treatment limb of the 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 with each respectively. 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 End Points) 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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Department of Medicine, Medical College of Virginia of Virginia Commonwealth University, Richmond, VA 23298, USA. dsica@hsc.vcu.edu
D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D017408:Guidelines as Topic; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D008297:Male; D016032:Randomized Controlled Trials as Topic / Q000592:standards*; D018570:Risk Assessment; D013375:Substance Withdrawal Syndrome; D013997:Time Factors
D000959:Antihypertensive Agents