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cakhatri ★ India, 2013-04-22 13:13 (4816 d 06:56 ago) Posting: # 10451 Views: 5,073 |
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Dear members, We are planning to conduct a reference - replicate design study as per USFDA requirements for submission to Health Canada. According to the information available from Health Canada's recent guidelines there is no specific requirement for reference replicate design with respect to the statistical evaluation. Are there any other guidelines from Health Canada to address the statistical requirements or a study planned as per FDA requirements would be acceptable by Health canada. Regards Chirag |
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Helmut ★★★   Vienna, Austria, 2013-04-22 14:53 (4816 d 05:15 ago) @ cakhatri Posting: # 10453 Views: 4,377 |
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Hi Chirag! ❝ We are planning to conduct a reference - replicate design study as per USFDA requirements for submission to Health Canada. Already knowing differences in regulatory requirements what’s the point to plan a study according to country A’s guidance(s) for submission to country B?  Canada currently does not accept reference-scaling for HVDs/HVDPs – which is the main purpose of replicate designs. If you want to submit the study later on to the FDA as well you can use a replicate design (Health Canada TPD guidance Section 2.3.1) Replicated cross-over designs may also be used, where the formulations are tested more than once in the same subjects. and evaluate it by conventional (unscaled) ABE. Make sure to power the study for Canada’s requirements: 90% CI of AUC within 80-125%, PE of Cmax within 80–125% (see also this thread).— 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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cakhatri ★ India, 2013-05-17 13:37 (4791 d 06:31 ago) @ Helmut Posting: # 10597 Views: 4,129 |
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Dear Helmut, The product has already passed with reference replicate design as per USFDA guidelines. The decision to conduct pivotal as reference replicate design was based on the pilot study data. The same product now needs to be marketed in Canada and therefore partial replicate design is the only choice as it does not meet BE with a 2-way crossover design. Is there an alternate, by any chance has Health Canada approved any BE study with partial replicate design that you might have come across.. Regards Chirag |
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Helmut ★★★ Vienna, Austria, 2013-05-17 16:05 (4791 d 04:04 ago) @ cakhatri Posting: # 10598 Views: 4,219 |
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Hi Chirag! ❝ The same product now needs to be marketed in Canada and therefore partial replicate design is the only choice as it does not meet BE with a 2-way crossover design. I don’t get your point. You have to pass ABE in Canada – irrespective of design. Why do you think that a study will fail in a 2×2 and pass in a replicate? In the former case the study was simply underpowered. You need ~¾ of the 2×2 sample size in a three-period replicate and ~½ in a four-period replicate to obtain the same power. But the number of treatments (and study costs) will be roughly the same. ❝ Is there an alternate, by any chance has Health Canada approved any BE study with partial replicate design that you might have come across.. No. Don’t mix up replicate designs with reference-scaled ABE. The fact that replicate designs are acceptable in Canada does not imply scaling (see my first post). You have to meet Canada’s requirements for ABE: 90% CI of AUC with 80.0–125.0% and the PE of Cmax within 80.0–125.0% (no CI required!). BTW, the partial replicate design is an awful model – it might be possible for any software (SAS, Phoenix, R) failing to converge (search the forum). If that happens you are in serious trouble. You have data which you cannot evaluate by any means.  I would suggest full replicates only (either RTRT|TRTR or TRT|RTR). — Dif-tor heh smusma 🖖🏼 Довге життя Україна! Helmut Schütz The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes |
Ing. Helmut Schütz