Synthetic estimators with moderating influence: the carry-over in cross-over trials revisited.
A general approach to combining alternative estimators of a parameter is described and applied to the analysis of 2x2 cross-over trials in which the treatment effect is of principal interest and carry-over is a nuisance feature. The approach requires prior information about the carry-over. Although modest information is sufficient, more information is rewarded by greater efficiency. The combination, or synthetic, estimator exhibits a moderating influence: its mean squared error is a flat function of the carry-over effect in the range of its feasible values, and for the largest feasible carry-over effect it is superior to either of the originally considered estimators. An extension of the approach is outlined and two other applications in medical research discussed. Although the method can be regarded as Bayesian in spirit, we focus on its resampling (frequentist) properties.
Longford
N T
NT
Department of Medical Statistics, De Montfort University, Leicester, UK. ntl@dmu.ac.uk
D001699:Biometry; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D018592:Cross-Over Studies; D006801:Humans; D013810:Therapeutic Equivalency; D016896:Treatment Outcome