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

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.

Keywords: Cholesterol lowering; Clinical trials; Statins; Time to benefit.