Bioequivalence and Bioavailability Forum

Hi Achievwin,

diving deeper into the matter. I was guessing your example and show the syntax Detlew mentioned above:

library(PowerTOST)
power.TOST(CV = 0.73, design = "parallel", n = 424)         # total sample size
[1] 0.8511768
power.TOST(CV = 0.73, design = "parallel", n = c(212, 212)) # vector of group sizes
[1] 0.8511768

Identical…

If you are interested in post hoc power (I hope your aren’t…), always give the vector of group sizes. If you give the total sample size, the functions of PowerTOST try to keep groups (or sequences in crossovers) as balanced as possible. If your study was more unbalanced, it will calculate a power which is slightly higher than the true one.

library(PowerTOST)
n <- sampleN.TOST(CV = 0.73, targetpower = 0.85, design = "parallel")[["Sample size"]]

+++++++++++ Equivalence test - TOST +++++++++++
            Sample size estimation
-----------------------------------------------
Study design: 2 parallel groups
log-transformed data (multiplicative model)

alpha = 0.05, target power = 0.85
BE margins = 0.8 ... 1.25
True ratio = 0.95,  CV = 0.73

Sample size (total)
 n     power
424   0.851177
So far, so good. But what about dropouts? Generally you dose more subjects and the number of eligible subjects will not be exactly as anticipated…

do.rate  <- 0.1           # anticipated dropout-rate 10% in both groups
n.adj    <- ceiling(n / (1 - do.rate)) # adjust the sample size and round up (conservative)
do.act   <- c(0.12, 0.08) # actual dropout-rates in groups
eligible <- round(n.adj / 2 * (1 - do.act))
cat("total sample size       :", n, paste0("(", n / 2, " per group)"),
    "\nanticipated dropout-rate:",
    sprintf("%.3g%% (in both groups)", 100 * do.rate),
    "\ndosed subjects          :",
    sum(dosed), paste0("(", n.adj / 2, " in both groups)"),
    "\nactual dropout-rates    :",
    sprintf("%.3g%% total", 100 * (1 - sum(eligible) / n.adj)),
    paste0("(", paste(sprintf("%.3g%%", 100 * do.act), collapse = " and "),
    " in the groups)"),
    "\ntotal eligible subjects :", sum(eligible),
    paste0("(", paste(eligible, collapse = " and "), " in the groups)"), "\n")

total sample size       : 424 (212 per group)
anticipated dropout-rate: 10% (in both groups)
dosed subjects          : 472 (236 in both groups)
actual dropout-rates    : 9.96% total (12% and 8% in the groups)
total eligible subjects : 425 (208 and 217 in the groups)

power.TOST(CV = 0.73, design = "parallel", n = sum(eligible)) # guessing
Unbalanced design. n(i)=213/212 assumed.
[1] 0.8519593
Note the message!

power.TOST(CV = 0.73, design = "parallel", n = eligible)      # exact
[1] 0.8518124

The functions of PowerTOST cannot ‘know’ whether a study was unbalanced. It guesses that only if the total sample size is odd (parallel design) or not a multiple of the number of sequences (crossovers). Otherwise, you don’t get a message like above (because in a parallel design it assumes that n₁ = n₂ = n/2). Try this one:

do.rate  <- 0.10
do.act   <- c(0.125, 0.095)

total sample size       : 424 (212 per group)
anticipated dropout-rate: 10% (in both groups)
dosed subjects          : 472 (236 in both groups)
actual dropout-rates    : 11% total (12.5% and 9.5% in the groups)
total eligible subjects : 420 (206 and 214 in the groups)

power.TOST(CV = 0.73, design = "parallel", n = sum(eligible))
[1] 0.8479974
No message, estimate too high because n₁ = n₂ = n/2 = 210 is assumed!

power.TOST(CV = 0.73, design = "parallel", n = eligible)
[1] 0.8478754