SAS: LSMEANS and ESTIMATE options [Software]

posted by vijay – 2009-04-21 04:03 (6267 d 17:10 ago) – Posting: # 3571
Views: 11,617

Hello All,
I have a few questions regarding the implementation and interpretation of PROC MIXED.
  1. What is the default multiple pairwise comparison adjustment used in PROC MIXED when we specify "LSMEANS TRT/pdiff cl" where we have more than 2 treatments? The SAS manual says that there is a default adjustment of all pairwise differences, but does not state what it is. So, I am assuming that confidence intervals produced in output "Difference of least square means" is based on some pairwise adjustment (This is not labeled ). But let's say my LSMEANS statement is “LSMEANS TRT/pdiff cl ADJUST=BON", which is bonferroni adjustment, the output states that adjustment has been made and gives both the adjusted and unadjusted values for the confidence intervals. As such is there a recommended procedure when more than 2 treatments are used.
  2. Is it redundant to use the ESTIMATE statement with contrasts, "ESTIMATE 't-r' -1 1/cl alpha=0.1' and 'LSMEANS TRT/pdiff cl alpha=0.1' in the same model. I notice that the point estimates and it's corresponding confidence intervals at the same alpha level given in the ESTIMATE part of the output for the contrast is similar to "Difference of LSMEANS" output unless a specific ADJUST= option is provided in the LSMEANS statement.
  3. I am frequently getting almost similar estimates for the standard errors of the point estimates in both the ESTIMATE and LSMEANS output. The SAS manual states, "The approximate standard errors for the LS-mean is computed as the square root of L(X'V-1X)-L'." I am assuming that the similar standard errors for the point estimates has something to do with the specification of the L matrix given that the X comes from the data. Please correct me if I am wrong. (One can find such similar estimates of SE in all outputs in chapter 4 of "Bioequivalence and Statistics in Clinical Pharmacology by Patterson and Jones").
  4. Finally, I may be totally naïve in asking this question but I still need to clarify :-). Does one use the actual AUC and Cmax parameters or the dose normalized AUC and Cmax parameters while assessing bioequivalence. Is there any difference? (I should have checked myself, just realized while writing this :-P). If we consider a scenario where a lesser dose of a new formulation (say 7.5 mg) is being tested against an old formulation (say 10 mg), then we do not need to dose normalize on the presumption that the new formulation is designed to perform as good as the old formulation but with a lesser dose due to better bioavailability.

Thanks in advance.
Vijay

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