What your Loewe Combination Index is not telling you
John Peterson
Presented at Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, November 17th, Bethesda, MD.
The use of baseline covariates in cross-over studies
Michael Kenward and James Roger
Published in Biostatistics, 2009, 0 (0), 1–17
Abstract: It is our experience that in many settings, crossover trials that have within-period baseline measurements are analyzed wrongly. A “conventional” analysis of covariance in this setting uses each baseline as a covariate for the following outcome variable in the same period but not for any other outcome. If used with random subject effects such an analysis leads to biased treatment comparisons; this is an example of cross-level bias. Using a postulated covariance structure that reflects the symmetry of the crossover setting, we quantify such bias and, at the same time, investigate potential gains and losses in efficiency through the use of the baselines. We then describe alternative methods of analysis that avoid the crosslevel bias. The development is illustrated throughout with 2 example trials, one balanced and orthogonal and one highly unbalanced and nonorthogonal.
John Peterson and Kevin Lief
Presented at Annual Meeting of the American Institute of Chemical Engineers, Nashville, TN, 8 Nov 2009
