Bioequivalence and Bioavailability Forum

Dear All,

We have conducted a 12 subjects biostudy. From the concentration time data it was observed that for some subjects data was missing at 96 and 120 hr time point and for other subjects data was missing for 72 and 168 hrs. There are certain subjects for whom 48 hr observation is missing. Data corresponding to these time points is missing either in Period 1 or Period 2 or in both the periods.

Now my question is how to treat the absent value (e.g. corresponding to 96 and 120hr) while feeding the data in WinNonlin. Some Options comes to my mind are:

1. Just write Missing in place of Absent corresponding to 96 and 120hr data point and follow the usual procedure of NCA to generate the PK Parameters.
   
   
2. Other option can be exclude all the data form 96 hr onward when sampling was done upto 216 hr for both the periods and follow the usual procedure of NCA to generate the PK Parameters.

I have asked the same question to Parsight support but was not satisfied from their answer.
Parsight reply to my question was

"We suggest that ........ the 96 and 120 observation rows for both test and reference should be excluded prior to running the NCA."

From their reply again question comes to my mind is

If I follow suggested approch (in red) then for different subjects I will have different sampling points at least for the NCA analysis i.e. for some subjects sampling scheme would be 0, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 10, 12, 16, 24, 48, 72, 144, 168, 216 and for other subjects sampling scheme would be 0, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 10, 12, 16, 24, 48, 96, 120, 144, 216. Like wise for some subjects sampling scheme would look like 0, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 10, 12, 16, 24, 72, 96, 120, 144, 168, 216.

Now my question is,

1. Is it write or wrong to have different time points for different subjects in the same study?
   
2. My second question is what is wrong with the first approach which I have suggested i.e. Just write missing in place of absent corresponding to 96 and 120hr data point for Period 1 and follow the usual procedure of NCA to generate the PK Parameters.

Please suggest me the correct way of tackling this issue. Please provide some detail or literature in support of your answer.

Waiting for your invaluable response.

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Edit: Category changed. [Helmut]