Comparing the efficacy, exposure, and cost of clinical trial analysis methods

This study aimed to compare three commonly used analysis methods for clinical trials in epilepsy in terms of statistical efficiency, nonefficacious exposure, and cost. A realistic seizure diary simulator was employed to produce 102 000 trials, which were analyzed by the 50%-responder rate method (RR50), median percentage change (MPC), and time to prerandomization (TTP). Half the trials compared a placebo to a drug that was 20% better, and the other half compared two placebos. The former were used to calculate statistical power; the latter were used for type 1 error rates. Based on the number of patients needed to achieve 90% power, expected number of patient-days of nonefficacious exposures and expected cost were calculated for each method. MPC demonstrated the highest efficacy, lowest exposure, and lowest cost. RR50 demonstrated the lowest efficacy, highest exposure, and highest cost. Costs were: MPC $1 295 000, TTP $1 315 720, and RR50 $2 331 000. Selecting an optimal analysis method for a primary outcome in an epilepsy trial can have consequences in terms of nonefficacious exposure and cost. This study provides evidence supporting the use of MPC (preferred) or TTP, and evidence suggesting that RR50 would incur high costs and excess exposures.