Philip J Barter1, David D Waters2. 1. From the School of Medical Sciences, University of New South Wales, Sydney, Australia; Division of Cardiology, Zuckerberg San Francisco General Hospital, San Francisco, CA, USA. 2. From the School of Medical Sciences, University of New South Wales, Sydney, Australia; Division of Cardiology, Zuckerberg San Francisco General Hospital, San Francisco, CA, USA. Electronic address: David.Waters@ucsf.edu.
Abstract
BACKGROUND: Time to benefit (TTB) in clinical trials of cholesterol-lowering drugs is important because it may provide a clue as to the potential mechanism of action of the drug, it is helpful in determining when to stop a trial for futility, and it may inform treatment decisions in subjects with reduced life expectancy. OBJECTIVE: To compare TTB among clinical trials of cholesterol-lowering drugs. METHODS: We examined TTB in 24 trials of cholesterol-lowering drugs with positive outcomes. Benefit curves were constructed by subtracting the curve for a placebo or comparator drug from the curve for active treatment. RESULTS: TTB ranged from 1 to 30 (mean 13.1) months, being shorter in trials of statins (n = 17) compared to nonstatins (n = 7), 10.3 vs 20.0 months. Among statin trials, TTB was shorter with atorvastatin (n = 6) than in trials with other statins (n = 11), 4.75 compared to 11.4 months. CONCLUSIONS: TTB is variable among trials of cholesterol-lowering drugs, being shorter with statin compared to nonstatin drugs. TTB is shorter with atorvastatin than with other statins. For trials of new cholesterol-lowering drugs, outcome curves that do not separate for up to 30 months do not preclude eventual benefit.
BACKGROUND: Time to benefit (TTB) in clinical trials of cholesterol-lowering drugs is important because it may provide a clue as to the potential mechanism of action of the drug, it is helpful in determining when to stop a trial for futility, and it may inform treatment decisions in subjects with reduced life expectancy. OBJECTIVE: To compare TTB among clinical trials of cholesterol-lowering drugs. METHODS: We examined TTB in 24 trials of cholesterol-lowering drugs with positive outcomes. Benefit curves were constructed by subtracting the curve for a placebo or comparator drug from the curve for active treatment. RESULTS:TTB ranged from 1 to 30 (mean 13.1) months, being shorter in trials of statins (n = 17) compared to nonstatins (n = 7), 10.3 vs 20.0 months. Among statin trials, TTB was shorter with atorvastatin (n = 6) than in trials with other statins (n = 11), 4.75 compared to 11.4 months. CONCLUSIONS:TTB is variable among trials of cholesterol-lowering drugs, being shorter with statin compared to nonstatin drugs. TTB is shorter with atorvastatin than with other statins. For trials of new cholesterol-lowering drugs, outcome curves that do not separate for up to 30 months do not preclude eventual benefit.
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