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brijeshmaroj ☆ 2011-02-08 08:16 (5612 d 22:53 ago) Posting: # 6577 Views: 5,328 |
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Hi there, In BA/ BE studies, we usually dose approximately n=10% more than the required sample size to take care of the withdrawals and drop outs to meet the required sample size at the end of the study. But are there any guidelines for ethical considerations for this? And if those extra subjects also complete the study, what is the justification for including/ excluding these extra subjects' samples for bioanalysis and including their data in statistical analysis. Do we have any regulatory guidelines for this? Thank you, Dr. Brijesh. Edit: Category changed. [Helmut] |
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Ohlbe ★★★ France, 2011-02-08 11:10 (5612 d 20:00 ago) @ brijeshmaroj Posting: # 6581 Views: 4,332 |
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Dear Dr Brijesh, ❝ But are there any guidelines for ethical considerations for this? Not that I know of. But you need to justify your sample size. Taking care of drop-outs is part of it (it would be unethical to fail to demonstrate BE just because 2 subjects dropped from the study). On the other hand you can (or rather, should) adapt the number of extra subjects to the known tolerability of the drug, and to the study design. If it is known to be create emesis, or if you have more than 2 periods, or a long wash-out, you will add more subjects. If the tolerability is known to be good and the study is "standard", you may not need 10 % extra. ❝ And if those extrasubjects also complete the study, what is the justification for including/excluding these extra subjects' samples for bioanalysis including theirdata in statistical analysis. Do we have any regulatory and guidelines for this? The EU guideline is very clear: The data from all treated subjects should be treated equally. It is not acceptable to have a protocol which specifies that 'spare' subjects will be included in the analysis only if needed as replacements for other subjects who have been excluded. It should be planned that all treated subjects should be included in the analysis, even if there are no drop-outs. Regards Ohlbe — Regards Ohlbe |
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brijeshmaroj ☆ 2011-02-08 12:18 (5612 d 18:52 ago) @ Ohlbe Posting: # 6585 Views: 4,489 |
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Dear Ohlbe, Thanks for giving me the precise reference. Could you please also let me know, if this is the same requirement as far as the FDA requirements are concerned. Has FDA mentioned this requirement anywhere in their guidance. Thanks a lot for your help. Best regards, Dr. Brijesh |
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Helmut ★★★   Vienna, Austria, 2011-02-08 13:47 (5612 d 17:23 ago) @ brijeshmaroj Posting: # 6590 Views: 4,320 |
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Dear Brijesh! ❝ Could you please also let me know, if this is the same requirement as far as the FDA requirements are concerned. Has FDA mentioned this requirement anywhere in their guidance. Do you know the Guideline Collection? Why don't you do your homework first? Sponsors should enter a sufficient number of subjects in the study to allow for dropouts. Because replacement of subjects during the study could complicate the statistical model and analysis, dropouts generally should not be replaced. Sponsors who wish to replace dropouts during the study should indicate this intention in the protocol. The protocol should also state whether samples from replacement subjects, if not used, will be assayed. If the dropout rate is high and sponsors wish to add more subjects, a modification of the statistical analysis may be recommended. Additional subjects should not be included after data analysis unless the trial was designed from the beginning as a sequential or group sequential design. Do you see the differences to EMA?— 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 |
Ing. Helmut Schütz