Nonparametric inference for time-dependent incremental cost-effectiveness ratios.

As the costs of medical care increase, more studies are evaluating cost in addition to effectiveness of treatments. Cost-effectiveness analyses in randomized clinical trials have typically been conducted only at the end of follow-up. However, cost-effectiveness may change over time. We therefore propose a nonparametric estimator to assess the incremental cost-effectiveness ratio over time. We also derive the asymptotic variance of our estimator and present formulation of Fieller-based simultaneous confidence bands. Simulation studies demonstrate the performance of our point estimators, variance estimators, and confidence bands. We also illustrate our methods using data from a randomized clinical trial, the second Multicenter Automatic Defibrillator Implantation Trial. This trial studied the effects of implantable cardioverter-defibrillators on patients at high risk for cardiac arrhythmia. Results show that our estimator performs well in large samples, indicating promising future directions in the field of cost-effectiveness.