Statistica Sinica 23 (2013), 1775-1791

SEQUENTIAL METHODS FOR COMPARATIVE

EFFECTIVENESS EXPERIMENTS:

POINT OF CARE CLINICAL TRIALS

Mei-Chiung Shih$^{1,2}$ and Philip W. Lavori$^{1}$

$^1$Stanford University and

$^2$VA Palo Alto Cooperative Studies Program Coordinating Center

Abstract: The goal of comparative effectiveness research (CER) is to support evidence-based choices of treatments. Currently the majority of randomized trials for CER are designed to demonstrate superiority, which often require large sample size because the effect sizes between treatments in current use are typically small to moderate and there are usually more than two treatments to be compared. We propose an alternative group sequential design for such setting. Instead of testing superiority, we aim to select high quality treatments that are within a small distance from the best treatment. The basic idea is to eliminate non-promising treatments at interim analyses that cannot be much better than the currently observed best treatment, based on generalized likelihood ratio tests. This approach can also be used for guideline implementation and for phase II selection trials.

Key words and phrases: Comparative effectiveness research, generalized likelihood ratio, guideline implementation, phase II-III trials, point of care clinical trials, sequential design.