GMR, theta 0 and that all [Two-Stage / GS Designs]

posted by Silva – Portugal, 2017-03-09 12:38  – Posting: # 17145
Views: 9,393

Dear d_labes
Many thanks for your explanations. So just to clarify my mind…
Using theta0 in power2stage as 0.8 or 1.25, I’m informing the system that, after studies have been simulated based on expected GMR, n1, CV and target power, test product is truly non bioequivalent, because true T/R is 0.8 or 1.25 and therefore the respective 90% CI will always be outside the [0.80.1.25] bioequivalence range.
The algorithm will then calculate the number of simulated studies that wrongly rejected the Null Hypothesis and divide this number by the total number of simulated studies. The ratio represents TIE.

Considering a study design under Potvin’s method B framework (type I TSD), i.e. and expected GMR of 0.95, an n1 between 12 and 60 subjects, a CV between 10 and 100% and a target power of 0.8, no simulations are required if, on the end of the study, GMR was 0.95 and CV between 10 and 100%. Am I thinking appropriately?
But if expected GMR is for example 0.91, n1 between 12 and 60 subjects, CV between 10 and 100% and target power is 0.8, there is a violation of method B assumptions, right?
And therefore simulations are needed based on true data at the end of trial in order to calculate if TIE was below the nominal alpha of 0.05. So, assuming a final GMR of 0.91, a CV of 34%, n1 = 16, a target power of 0.8, and no futility rule, power2stage simulation conditions would be:
power.2stage(method = c("B"), alpha0 = 0.05, alpha = c(0.0294, 0.0294),n1=16, GMR=0.91, CV=0.34, targetpower = 0.8, pmethod = c("nct"), usePE = FALSE, Nmax = Inf, min.n2=0, theta0=0.8, theta1=0.8, theta2=1.25, npct = c(0.05, 0.5, 0.95), setseed = TRUE, details = TRUE)
With this simulation scenario:
1e+05 sims. Stage 1 - Time consumed (secs):
   user  system elapsed
    0.4     0.0     0.4
Keep calm. Sample sizes for stage 2 (98482 studies)
will be estimated. May need some time.
Time consumed (secs):
   user  system elapsed
    1.3     0.0     1.3
Total time consumed (secs):
   user  system elapsed
      2       0       2

Method B: alpha (s1/s2) = 0.0294 0.0294
Target power in power monitoring and sample size est. = 0.8
BE margins = 0.8 ... 1.25
CV = 0.34; n(stage 1)= 16; GMR = 0.91
GMR = 0.91 and mse of stage 1 in sample size est. used
Futility criterion Nmax = Inf

1e+05 sims at theta0 = 0.8 (p(BE)='alpha').
p(BE)    = 0.04385
p(BE) s1 = 0.01512
Studies in stage 2 = 98.48%

Distribution of n(total)
- mean (range) = 100.5 (16 ... 332)
- percentiles
 5% 50% 95%
 46  96 170


Based on this results:Am I interpreting correctly this results?
Best rgs and thks for all the patience!

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