Variations in time to benefit among clinical trials of cholesterol-lowering drugs

•Time to benefit (TTB) is quite variable across trials of lipid-lowering drugs. •TTB appears to be shorter with statins than with other drugs. •Among statin trials, TTB is shorter with atorvastatin than with other statins. •For new trials, curves that do not separate for 24-30 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. 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. To compare TTB among clinical trials of cholesterol-lowering drugs. 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. 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. 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.