PE vs GMR in Bear [🇷 for BE/BA]
❝ Very often I face with that in BE study reports submitted to EMA/FDA by different companies GMR is the metric, not PE (along with its CIs). This is the reason why I interested in what we really "calculate" and why, is it specific of particular software or using of different terminology or something else.
Even if you look into EMA guideline:
The assessment of bioequivalence is based upon 90% confidence intervals for the ratio of the population geometric means (test/reference) for the parameters under consideration.
The geometric mean ratio (GMR) should lie within the conventional acceptance range 80.00-125.00%.
They are using 'geometric means', 'geometric mean ratio' terms, but adjusted means (aka LSMeans) should be taken into account instead. As an example please see the code and conclusions in EMA PKWP Q&A
❝ In a BE study report there is a summary table for presenting BE results, where geometric means (or LSMEANs?) in natural scale, GMR (%) (or PE(%)?) and CI(%) should be reported.
❝ MEAN-ref = 3.970504
❝ MEAN-test = 4.097524
❝ MSE = 0.1563787
❝ SE = 0.08338823
❝ Estimate(test-ref) = 0.1282001
❝ Point Estimate CI90 lower CI90 upper
❝ 113.678 98.809 130.785
❝ As Yung-jin explained me that PE in R/bear is not a direct arithmetic difference, and it is estimated in a specific linear model in ANOVA.
Let's wait for Yung-jin's comments
❝ << PK Parameter Summaries >>
❝ summary Test Ref Ratio
❝ LSMEAN 4.097 3.971 1.043
MEAN-test = 4.097524 which could be rounded to 4.098, not 4.97
❝ So, Exp(LSMEAN[T])=60.159 and Exp(LSMEAN[R])=53.038, and these are geometric means, right?
❝ Does my understanding correct now?
❝ But what to report to authorities? PE or GMR? For balanced study they are equal, but for imbalanced they are slightly different.
You can try to add a footnote and describe somewhere why GeoMeans could be unequal to LSMeans
❝ And what about CIs? Should I construct them for GMR as well?
- PE vs GMR roman_max 2018-12-10 17:53 [🇷 for BE/BA]
- PE vs GMR Ohlbe 2018-12-11 00:28
- PE vs GMR mittyri 2018-12-11 16:30
- PE vs GMR roman_max 2018-12-12 16:41
- PE vs GMR ElMaestro 2018-12-12 21:39