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Ken Peh ★ Malaysia, 2014-03-27 20:14 (4077 d 03:07 ago) Posting: # 12731 Views: 7,938 |
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Dear All, Appreciate to have your feedback on the following questions.
Regards, Ken |
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Ohlbe ★★★ France, 2014-03-31 12:54 (4073 d 11:28 ago) @ Ken Peh Posting: # 12742 Views: 6,826 |
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Dear Ken, ❝ Do we have to reject the standard curve if the LLOQ and the standard next to LLOQ are out of the range ? EMEA guideline allows throwing 2 out of 8 standard calibrators. In this case, the criteria is fulfilled ? Most of the time the low QC sample is placed between the 2nd and 3rd calibration samples. If you exclude the first 2 calibration samples, the third becomes the LLOQ, and you loose your LQC. Impossible to validate the run. ❝ When we reanalyze the study samples, what is the criteria to accept the value of reanalyzed sample and reject the initial value ? Can we pick the initial concentration if the difference between the reanalyzed concentration and the initial concentration is less than 20% ? Thank you. It depends what the reason was to reanalyse the sample. Analytical reason : if you consider the first value to be unreliable, pick the repeat value, even if close to the initial value. For PK repeats or confirmation of weird data (not to be done for EU submissions): you can keep the initial concentration if confirmed by the second. In any case the decision tree should be well defined in your SOP, or you could be accused of cherry picking. — Regards Ohlbe |
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Ken Peh ★ Malaysia, 2014-03-31 20:41 (4073 d 03:41 ago) @ Ohlbe Posting: # 12745 Views: 6,762 |
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Dear Ohlbe, Thank you very much. Regards, Ken |
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Ken Peh ★ Malaysia, 2014-04-01 20:36 (4072 d 03:46 ago) @ Ohlbe Posting: # 12752 Views: 6,794 |
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Dear Ohlbe, ❝ It depends what the reason was to reanalyse the sample. Analytical reason : if you consider the first value to be unreliable, pick the repeat value, even if close to the initial value. For PK repeats or confirmation of weird data (not to be done for EU submissions): you can keep the initial concentration if confirmed by the second. Do we need to inject the third time if the repeat value and the initial value are far apart ? I have seen some CROs inject the third time to confirm whether the repeat or the initial value should be picked. How far the difference in value between repeat and initial value to justify for the third injection ? ❝ In any case the decision tree should be well defined in your SOP, or you could be accused of cherry picking. How detail we should write in our SOP ? Besides SOP, can we define in in-house guideline ? Appreciate your comments. Thank you. Regards, Ken |
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Ohlbe ★★★ France, 2014-04-01 21:12 (4072 d 03:10 ago) @ Ken Peh Posting: # 12753 Views: 6,735 |
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Dear Ken, ❝ Do we need to inject the third time if the repeat value and the initial value are far apart ? I have seen some CROs inject the third time to confirm whether the repeat or the initial value should be picked. If the repeat was for an analytical reason: no. If it was a PK repeat or anomalous value: yes, I would do a 3rd analysis. Or actually, I would rather do the repeat analysis in duplicate. ❝ How far the difference in value between repeat and initial value to justify for the third injection ? There is nothing written in any guideline... ❝ How detail we should write in our SOP ? Besides SOP, can we define in in-house guideline ? You can call it an SOP, or internal guideline, or whatever. But it needs to be defined in writing in advance, in a controlled document which is part of your quality system, with clear decision rules for each type of repeat and the various situations. — Regards Ohlbe |
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Ken Peh ★ Malaysia, 2014-06-23 11:09 (3989 d 13:12 ago) @ Ohlbe Posting: # 13122 Views: 6,480 |
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Dear Ohlbe, Would highly appreciate your comments again on sample reanalysis. If the repeat is for analytical reason, and the 2nd value is far apart from the initial value, how do we justify the acceptance of the 2nd value ? What are the analytical reasons that can be given ? QCs passed. ❝ ❝ How far the difference in value between repeat and initial value to justify for the third injection ? If the repeat is for abnormal value, if we repeat in duplicate, which repeat should be taken, the 2rd or the 3nd repeat ?? is the purpose of 3rd repeat for confirmation ? Then, we should take the 2rd repeat as final value ? Have you ever come across a scenario that the 3rd repeat is different from the 2rd repeat ? Again, what is the specification or criteria we need to set to accept the value ? Can we use ISR as a guide, set 20% as acceptance value ? How do we justify to inspector on this issue ? Thank you. Regards, Ken |
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Ohlbe ★★★ France, 2014-07-03 01:21 (3979 d 23:01 ago) @ Ken Peh Posting: # 13203 Views: 6,325 |
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Dear Ken, Sorry for the delayed answer. ❝ If the repeat is for analytical reason, and the 2nd value is far apart from the initial value, how do we justify the acceptance of the 2nd value ? What are the analytical reasons that can be given ? QCs passed. If you re-analyse the sample for an analytical reason, that's normally because you consider that the initial value is not reliable (e.g. variation in IS response). Having a difference between the initial and the repeat value is somewhat expected. ❝ How far the difference in value between repeat and initial value to justify for the third injection ? Again, if the repeat analysis is for an analytical reason: if the first value is not reliable, why compare it to the second value ? ❝ If the repeat is for abnormal value, if we repeat in duplicate, which repeat should be taken, the 2rd or the 3nd repeat ?? is the purpose of 3rd repeat for confirmation ? Then, we should take the 2rd repeat as final value ? Several possibilities have been described, with decision trees which depend on the difference between the 1st, 2nd and 3rd values. Again, there is nothing described in any guidelines. You may be able to find decision trees published somewhere. Sorry I don't have any reference to provide. ❝ Have you ever come across a scenario that the 3rd repeat is different from the 2rd repeat ? Again, what is the specification or criteria we need to set to accept the value ? Yes, sure, it happens. That's part of the decision trees... You may get in a situation where the value is not reportable, if there is too much difference between the 3 results. ❝ How do we justify to inspector on this issue ? Show the inspector your SOP... And if they're not happy with your decision tree, show them where it comes from. — Regards Ohlbe |
Ing. Helmut Schütz