Cardiac safety study requirements apply to almost all drugs in every therapeutic area, not just cardiology. Their aim is to prevent the approval of drugs liable to increase the risk of sudden cardiac death from serious arrhythmias induced by novel agents with unrecognised electrophysiological effects.
These studies matter at every stage of drug development. Even at proof of concept, a biotechnology startup can increase investor interest by demonstrating electrocardiogram (ECG) safety up front. However, since the 1990s, guidance has evolved and uncertainty abounds regarding the correct testing approach. Here, we discuss cardiac safety best practices and how developers can avoid delays from lengthy QT studies as filing time approaches, when overheads are highest.
How Cardiotoxic Drugs Changed the Regulatory Landscape
In the 1990s, adverse event data flagged several drugs as potential cardiac bad actors. These were not obscure medications, but rather drugs with everyday applications. Terfenadine and astemizole were new, non-sedating antihistamines, grepafloxacin was a broad-spectrum antibiotic, and cisapride was a remedy for gastroesophageal reflux. These drugs in overdose, in patients with altered drug kinetics such as the elderly, or in certain drug combinations, caused QT interval prolongation and potentially fatal cardiac arrhythmias. Between 1998 and 2000, manufacturers withdrew these drugs from the market.
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