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bharathi ☆ India, 2014-09-16 14:19 (3502 d 06:20 ago) Posting: # 13519 Views: 4,097 |
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Dear All, I am performing fasting and fed Bioequivalence studies for an X product. Design of the study is parallel as recommended by the Agency. Fasting and Fed studies are divided each into 2 groups. Fed study was completed with 2 groups (Each group with 40 subjects, 20 each of test and reference. Analysis was done and proved to be bioequivalent. In fasting study, only group 1 is completed and there's no time for the group 2 to be completed. So can I analyze and if it is bioequivalent, will Agency accepts by proposal (deviation from the protocol that group 2 was not performed?) Please can you clarify the same Regards, Bharathi |
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Helmut ★★★   Vienna, Austria, 2014-09-16 15:07 (3502 d 05:31 ago) @ bharathi Posting: # 13520 Views: 3,294 |
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Hi Bharathi, ❝ Fed study was completed with 2 groups […] Analysis was done and proved to be bioequivalent. ❝ ❝ In fasting study, only group 1 is completed and there's no time for the group 2 to be completed. What do you mean by “there's no time”? I wouldn’t call that a reasonable justification. ❝ So can I analyze and if it is bioequivalent, will Agency accepts by proposal (deviation from the protocol that group 2 was not performed?) Depends on the Agency. You are aware that your power (i.e., chance to demonstrate BE in only ½ of the planned sample size) will substantially drop? Example: CVtotal 20%, GMR 0.95, nplanned 36, power 81.0% ⇒ nactual 18, power 42.7%. OK, the patient’s risk is not affected (and this is the regulator’s main concern) – but with such a low power you are playing havoc with the producer’s risk. What does the sponsor say? Even if you pass – a posteriori power is nonsense, but well, cough… Likely you will have to face questions from some regulators. I would expect that the chance of the study to fail is higher than to pass. Then what? You cannot post hoc switch to a Two-Stage Design. Repeat the study once you “have more time”? Remember you are treating human beings (patients?), not guinea pigs. The only option I see is not to perform the assessment of BE of the first group. Submit a substantial amendment to the agency + IEC stating that you will perform a Two-Stage Design*. Hope for the best (there is no guarantee whether they will swallow your justification). If you get the approvals, perform the analysis of group 1 and continue according to the decision tree of the framework. Be aware that it is very likely that a second group is required (low power in the first group expected), which – in the worst case – might lead to a total sample size substantially larger compared to the one you originally planned for. Good luck!
— 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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bharathi ☆ India, 2015-10-01 08:57 (3122 d 11:41 ago) @ Helmut Posting: # 15508 Views: 2,643 |
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Hi Friends, I want to update the status for my previous question. As an internal regulator of the firm, the approach doesn't sound good even for me... But have to do... (proceeded for analysis of first group) and the test product is found to be bioequivalent (sponsor's luck) The same was submitted to the agency. No RTR (refuse to receive) received and no bio query yet (again sponsor's luck). Regards, Bharathi Edit: THX for the update! [Helmut] |
Ing. Helmut Schütz