Imph
★

Algeria,
2023-07-02 13:33
(149 d 18:27 ago)

Posting: # 23645
Views: 1,257

## missing points around tmax [NCA / SHAM]

Hi,

can you please enlighten me on the most accepted way to handle missing points around tmax?

Helmut
★★★

Vienna, Austria,
2023-07-02 16:15
(149 d 15:45 ago)

@ Imph
Posting: # 23646
Views: 1,065

## Exclude the subject(s)

Hi Imph

❝ can you please enlighten me on the most accepted way to handle missing points around tmax?

Sorry, cards are stacked against you. I tried a lot with data imputation by PK modeling in the past, but nothing was accepted by agencies. However, if that doesn’t happen in many subjects, the loss in power when you exclude the subject(s) is generally not large (unless the number of eligible subjects becomes really small).

Examples:

library(PowerTOST) # 2x2x2 design defaults: T/R 0.9, target power 0.8 excl <- 0.05 # fraction of excluded subjects CV   <- seq(0.15, 0.35 0.05) x    <- data.frame(CV = CV, n = NA_integer_, power = NA_real_,                    elig = NA_real_, pow.elig = NA_real_, loss = NA_real_) for (j in 1:nrow(x)) {   tmp           <- sampleN.TOST(CV = CV[j], print = FALSE)   x$n[j] <- tmp[["Sample size"]] x$power[j]    <- tmp[["Achieved power"]]   x$elig[j] <- floor(x$n[j] * (1- excl))   x$pow.elig[j] <- suppressMessages(power.TOST(CV = CV[j], n = x$elig[j]))   x$loss[j] <- 100 * (1 - x$pow.elig[j] / x\$power[j]) } names(x)[4:6] <- c("eligibe", "power", "loss (%)") print(signif(x, 4), row.names = FALSE)    CV  n  power eligibe  power loss (%)  0.15 12 0.8305      11 0.7877    5.150  0.20 20 0.8347      19 0.8132    2.569  0.25 28 0.8074      26 0.7761    3.887  0.30 40 0.8158      38 0.7953    2.515  0.35 52 0.8075      49 0.7831    3.017

Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
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Imph
★

Algeria,
2023-07-04 12:15
(147 d 19:44 ago)

@ Helmut
Posting: # 23649
Views: 1,050

## predose sample is missing

My sincere thanks for your help.

Another question if I may, what about if predose sample is missing in period 1 or 2 in a crossover design?

Best regards.

Helmut
★★★

Vienna, Austria,
2023-07-04 12:25
(147 d 19:35 ago)

@ Imph
Posting: # 23650
Views: 1,005

## predose sample is missing

Hi Imph

❝ […] what about if predose sample is missing in period 1 or 2 in a crossover design?

Without a predose sample in period 1 it will be difficult to argue that there are no issues with the baseline. Similar for period 2 – needed to demonstrate lack of carry­over.

Therefor, exclude the subject(s).

Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
dshah
★★

India/United Kingdom,
2023-07-05 09:37
(146 d 22:23 ago)

@ Imph
Posting: # 23653
Views: 998

## predose sample is missing

HI Imph!

❝ Another question if I may, what about if predose sample is missing in period 1 or 2 in a crossover design?

How is it possible to miss the predose sample for period 1? If subject is going to be dosed- pre dose sample would be present. Dosing can always take place after pre-dose sample collection and dosing time difference can be considered for deviation.

Regards,
Divyen
Helmut
★★★

Vienna, Austria,
2023-07-05 11:08
(146 d 20:51 ago)

@ dshah
Posting: # 23654
Views: 972

## predose sample is missing

Hi Divyen,

❝ How is it possible to miss the predose sample for period 1? If subject is going to be dosed- pre dose sample would be present.

Vacutainer broken in centrifugation? Very rare but happens.

Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
Imph
★

Algeria,
2023-07-06 09:07
(145 d 22:53 ago)

@ Helmut
Posting: # 23656
Views: 930

## predose sample is missing

Hi,

❝ Vacutainer broken in centrifugation? Very rare but happens.

Exactely.

Thank you very much.
dshah
★★

India/United Kingdom,
2023-07-10 18:57
(141 d 13:02 ago)

@ Imph
Posting: # 23668
Views: 835

## predose sample is missing

Hi Imph!

I guess this sample should be considered as non reportable sample instead of missing sample. Missing sample indicates that samples are not withdrawn from subjects. If sample is taken but not analyzed or can not be reported due to XYZ reason- then they should be treated as N.R. and not as missing.
Regards,
Divyen
dshah
★★

India/United Kingdom,
2023-07-03 10:25
(148 d 21:34 ago)

@ Imph
Posting: # 23648
Views: 1,085

## missing points around tmax

Hi!
Generally CRO have SOP in place to handle such cases.
Regards,
Divyen