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Eligible patients underwent randomization by a computer program to determine the sequence of three crossover arms.
TEAEs with a change in severity across phases or that resolved and then restarted in the crossover phase were counted both in the dose-optimization and crossover arms.
Further data from the crossover arms of the BIG 1 98 trial may provide an answer to this question, but it will be several years before these data are mature.
In BIG 1-98, at a median follow-up of 8.0 years from random assignment, there was no significant difference between one of the crossover arms (tamoxifen followed by letrozole) versus letrozole alone, but there was a trend against starting with tamoxifen and then switching (DFS hazard ratio = 1.07; OS hazard ratio = 1.10; both P = 0.36; Table 2) [ 54].
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The patients allocated to the control group represent the crossover arm of the study.
The other BIG 1-98 crossover arm also addressed the question of tamoxifen after 2 to 3 years of letrozole.
Initially, we planned to implement a crossover arm for the CG in order to achieve the sample size as early as possible [ 28].
This was shown specifically by a crossover arm in a UFT/LV trial (Borner et al, 2002), but has also been reported in other studies, and was repeated by patient representatives advising the NICE committee on guidance recommendations.
Because of this low adherence and the ensuing cancellation of the crossover arm, it was not possible to assess the CG together with the IG in the follow-up evaluation.
A limitation of this study in assessing effect on cortisol is that it was a secondary endpoint in this study and the design was not optimized for measuring this parameter (e.g. it did not include a placebo crossover arm) and it is clear that there was a time effect in the study with a decline in cortisol concentrations between day −1 and day 7 in all ethnic groups, including Caucasians.
If a poacher need guns, for instance, here we have a crossover with arms trafficking.' Routes for trafficking ivory may also be used for trafficking weapons and the more profitable line may then be used to finance other ventures, Interpol say.
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Justyna Jupowicz-Kozak
CEO of Professional Science Editing for Scientists @ prosciediting.com