Bioequivalence and Bioavailability Forum

Dear All,

the paper by Willavize and Morgenthien, Nonparametric confidence intervals for Tmax in sequence-stratified crossover studies (Pharmaceutical Statistics 2008), has already been cited in this forum (for example here).

I tried to reproduce the results presented in the paper using the median scaling method (MS) and the simplified nonparametric methd (NP). Both these approaches, as stated in the sections 3 and 4.1, request the point estimates and the confidence limits to be divided by 2 as a final step. Since MS and NP provide estimates of 2*delta, twice the shift in location, this step is necessary to obtain estimates of delta.

I suppose that the results presented in Table II refer to delta. Please note that in this table also the estimates obtained from a simple ANOVA model (indicated as normal theory method, NT) are presented, and clearly their comparison with estimates of 2*delta would make little sense. However, with MS and NP I obtain exactly the same point estimates and confidence intervals reported in Table II skipping the division by 2. In my opinion, all the results presented in the table for MS and NP should be divided by 2 in order to obtain estimates of delta instead of estimates of 2*delta.

Maybe someone else who already tried to apply the methods described in the paper can help me clarify this point? If you are interested, I would be happy to share with you the SAS code used. Thank you very much for your help.