|| Checking for direct PDF access through Ovid
Recently adopted guidelines mandate the inclusion of detailed non-clinical and clinical QT data in future drug labels. As a result of increasing recognition of drug-induced proarrhythmias, and the bias introduced by the prescribing physician's awareness of these events, it is likely that the number of adverse drug reaction (ADR) reports of life-threatening ventricular arrhythmias and sudden death, allegedly caused by the drug, will increase. To illustrate how different approaches have been used to assess proarrhythmic liability and validate ADR reports on serious ventricular arrhythmias, this overview assesses pharmacoepidemiology studies on terfenadine and cisapride, the quality of ADR reports and the effect of label changes on prescribing patterns and other information to prescribing physicians. Clinical and pharmacoepidemiology studies, which in most cases did not demonstrate an increased risk for proarrhythmias with these two drugs, are discussed with emphasis on limitations, studied endpoints, and populations. Recommendations are made on how to improve the effectiveness of labelled precautions and contraindications, which may include the implementation of more effective alert systems. Given the low incidence of drug-induced proarrhythmias, ‘signal’ generation through ADR reports will continue to have a key role for early identification of proarrhythmic liability of newly marketed drugs. The quality of these reports varies widely, and can be improved through implementation of procedures by which complementary information is captured and events are adjudicated and classified into confidence categories using a consistent scheme across different classes of drugs.