Early stopping in clinical trials and epidemiologic studies for "futility": conditional power versus sequential analysis.
Early stopping of a clinical trial is well accepted when there is enough evidence for a significant effect. However, during the course of a trial, there can be reasons to consider early termination for "futility." In epidemiologic studies, costly or destructive laboratory tests or slow case accrual can make it desirable to stop a study early for reasons of efficiency. Estimation of the conditional power (CP) is proposed as a decision tool to stop a study early or to continue it. We consider the disadvantages of this method. We propose (group) sequential continuation of the trial or study as a less arbitrary strategy. We re-analyzed two data sets from the literature to illustrate the advantages of a sequential approach. We conclude that (group) sequential analyses have several advantages over CP. More studies should consider a sequential design and analysis to enable early stopping when enough evidence has accumulated to conclude a lack of the expected effect. Such a strategy can save valuable resources for more promising hypotheses.
van der Tweel
Ingeborg
I
Centre for Biostatistics, Utrecht University, Centrumgebouw Noord C122, Padualaan 14, 3584 CH Utrecht, The Netherlands. i.vandertweel@bio.uu.nl
van Noord
Paulus A H
PA
D000914:Antibodies, Viral / Q000097:blood; D001161:Arteriosclerosis / Q000821:virology; D016022:Case-Control Studies; D003661:Decision Support Techniques; D016021:Epidemiologic Studies; D006801:Humans; D008181:Lupus Nephritis / Q000628:therapy; D018447:Medical Futility; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D013223:Statistics as Topic
D000914:Antibodies, Viral