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Ken Peh ★ Malaysia, 2014-05-22 21:42 (4416 d 18:53 ago) Posting: # 12991 Views: 4,147 |
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Dear All, EMEA guideline mentions that "10% of the samples should be reanalysed in case the number of samples is less than 1000 samples and 5% of the number of samples exceeding 1000 samples. Furthermore, it is advised to obtain samples around Cmax and in the elimination phase". I would be glad to have your feedback and comments on the following questions:
Thank you. Regards, Ken |
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Helmut ★★★   Vienna, Austria, 2014-05-23 15:12 (4416 d 01:23 ago) @ Ken Peh Posting: # 12995 Views: 3,409 |
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Hi Ken, the idea of ISR is to obtain information about potential problems with reproducibility (metabolite interaction, sample homogeneity) within the entire range of concentrations. Obviously the highest concentrations are expected around Cmax and the lowest in the elimination phase. Some regulators expect samples to be selected before starting the analyses. This works only if
— Dif-tor heh smusma 🖖🏼 Довге життя Україна! ![[image]](https://static.bebac.at/pics/Blue_and_yellow_ribbon_UA.png) Helmut Schütz ![[image]](https://static.bebac.at/img/CC by.png) The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes |
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Ohlbe ★★★ France, 2014-05-24 22:16 (4414 d 18:19 ago) @ Helmut Posting: # 13006 Views: 3,326 |
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Dear Ken and Helmut, ❝ the idea of ISR is to obtain information about potential problems with reproducibility (metabolite interaction, sample homogeneity) within the entire range of concentrations. Obviously the highest concentrations are expected around Cmax and the lowest in the elimination phase. In addition you may get a different ratio of parent/metabolite, which may make metabolite back-conversion more visible. ❝ This works only if [...] I would add another potential problem to the list: what if the concentration in your elimination phase sample is BLQ ? One possibility to pre-define the samples to be re-analysed would be to write in the protocol that you will select the Cmax sample and the last sample with a concentration above 2 or 3 times the LLOQ. The samples themselves will not be listed, but the criteria used for selection would not leave any room for interpretation, which hopefully would be sufficient for regulators (or sponsors) who want the samples to be selected in advance. — Regards Ohlbe |
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Ken Peh ★ Malaysia, 2014-05-28 15:56 (4411 d 00:39 ago) @ Ohlbe Posting: # 13014 Views: 3,114 |
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Dear Helmut and Ohlbe, Thanks to both of you for the suggestions. Is it necessary to pick samples of all the subjects for ISR ? For example, if we have 30 subjects, do we need to run ISR of all the 30 subjects ? Can we have ISR from 24 subjects as long as we fulfill the requirement of the numbers in the guideline ?  Kindly comment. Thank you. Regards, Ken |
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Ohlbe ★★★ France, 2014-05-28 16:27 (4411 d 00:08 ago) @ Ken Peh Posting: # 13015 Views: 3,156 |
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Dear Ken, I don't think it is mandatory to have samples from each and every subject. It would be feasible in a BE trial but not in a Phase 3 trial or in preclinical studies anyway. However a representative number of subjects should be included: it would not be acceptable to re-analyse all samples from just a couple of subjects, as it would reduce the chances to see problems affecting only a limited number of subjects or of runs. — Regards Ohlbe |
Ing. Helmut Schütz