A note on the power of Fisher's least significant difference procedure.
Fisher's least significant difference (LSD) procedure is a two-step testing procedure for pairwise comparisons of several treatment groups. In the first step of the procedure, a global test is performed for the null hypothesis that the expected means of all treatment groups under study are equal. If this global null hypothesis can be rejected at the pre-specified level of significance, then in the second step of the procedure, one is permitted in principle to perform all pairwise comparisons at the same level of significance (although in practice, not all of them may be of primary interest). Fisher's LSD procedure is known to preserve the experimentwise type I error rate at the nominal level of significance, if (and only if) the number of treatment groups is three. The procedure may therefore be applied to phase III clinical trials comparing two doses of an active treatment against placebo in the confirmatory sense (while in this case, no confirmatory comparison has to be performed between the two active treatment groups). The power properties of this approach are examined in the present paper. It is shown that the power of the first step global test--and therefore the power of the overall procedure--may be relevantly lower than the power of the pairwise comparison between the more-favourable active dose group and placebo. Achieving a certain overall power for this comparison with Fisher's LSD procedure--irrespective of the effect size at the less-favourable dose group--may require slightly larger treatment groups than sizing the study with respect to the simple Bonferroni alpha adjustment. Therefore if Fisher's LSD procedure is used to avoid an alpha adjustment for phase III clinical trials, the potential loss of power due to the first-step global test should be considered at the planning stage.
Meier
Ulrich
U
Department of Medical Data Services/Clinical Biostatistics, Boehringer Ingelheim Pharma GmbH and Co. KG, Ingelheim am Rhein, Germany. meieru@ing.boehringer-ingelheim.com
D000704:Analysis of Variance; D001699:Biometry; D002986:Clinical Trials as Topic; D017326:Clinical Trials, Phase III as Topic; D003627:Data Interpretation, Statistical; D023381:Endpoint Determination; D006801:Humans; D015233:Models, Statistical; D015999:Multivariate Analysis; D010919:Placebos; D012106:Research; D012107:Research Design; D018401:Sample Size; D013678:Technology, Pharmaceutical / Q000379:methods*
D010919:Placebos