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Sereng ☆ USA, 2023-03-13 18:08 (640 d 12:00 ago) Posting: # 23494 Views: 4,870 |
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Dear colleagues, my associate is using the term "full replicate" to describe a four-way crossover BE study of Test (Fed), Test (Fasted), Reference (Fed) and Reference (Fasted), with each treatment given only once. In my view, this is not an appropriate us of the term "full replicate" but I want to be certain. Additionally, what is the appropriate term, "Full Replicate" or "Fully Replicate"? Regards — Biostatistically Challenged CEO |
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Mahmoud ★ Jordan, 2023-03-13 21:27 (640 d 08:41 ago) @ Sereng Posting: # 23495 Views: 4,433 |
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Dear Sir ========= You can use the following design 1 B-A-C-D-A-C 2 A-D-B-C-C-A 3 D-C-A-A-B-C 4 C-A-D-C-A-B 5 A-C-C-B-D-A 6 C-B-A-A-C-D SABE for fast and food accepted by FDA Six period with six sequences B= Test under fast A= Ref under fast D= Test under fed C= Ref under fed |
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Sereng ☆ USA, 2023-03-14 00:38 (640 d 05:30 ago) @ Mahmoud Posting: # 23496 Views: 4,457 |
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Hi Mahmoud, thank you for your response. I think you may have misunderstood my question. I have always understood a "full replicate" design to be one where each treatment condition is repeated twice. Therefore, if the Test was being compared with Reference in the fasted state, a full replicate would involve giving both the Test and Reference on two occasions. Is this correct? Furthermore, calling a four-way fed fasted crossover study (Test Fed & Fasted, and Ref Fed & fasted), each given once a Full Replicate study would be wrong. is this correct? — Biostatistically Challenged CEO |
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Mahmoud ★ Jordan, 2023-03-14 09:44 (639 d 20:24 ago) @ Sereng Posting: # 23497 Views: 4,365 |
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Dear Sir ======= If you neeed to genrate two studies fed and fast separately you can use the following design sequence 1 TRRT sequence 2 RTTR but the best to do only one study for fed and fast with six sequence and six period |
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Achievwin ★★ US, 2023-03-27 21:08 (626 d 10:00 ago) @ Mahmoud Posting: # 23513 Views: 4,024 |
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Dear Experts Can TRT, RTR be called two sequence full replicate in three way cross over? can it be a substitute for RTRT or TRTR, or TTRR or RRTT (in four period fully replicated design)? The goal is to do a 3-period cross-over yet to capture ISCV for Test and Reference separately. Can this type of design address RSABE for warfarin by FDA? (Nothing) Achievwin   |
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mittyri ★★ Russia, 2023-03-28 00:16 (626 d 06:52 ago) @ Achievwin Posting: # 23514 Views: 4,002 |
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Dear Achievwin! ❝ Can TRT, RTR be called two sequence full replicate in three way cross over? I would say in three periods. For me 'a way' is closer to the sequence (subject's way ). But that's just my feeling, I see many people are using it, so your wording is rather correct.❝ can it be a substitute for RTRT or TRTR, or TTRR or RRTT (in four period fully replicated design)? Bloody partial replicate goes away and is being substituted to that design in GL. I would opt for it. — Kind regards, Mittyri |
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Achievwin ★★ US, 2023-03-28 05:06 (626 d 02:02 ago) @ mittyri Posting: # 23516 Views: 3,955 |
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Fantastic advise thank you ❝ Bloody partial replicate goes away and is being substituted to that design in GL. I would opt for it. |
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Helmut ★★★   Vienna, Austria, 2023-03-28 11:03 (625 d 20:05 ago) @ mittyri Posting: # 23517 Views: 3,999 |
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Hi mittyri & Achievwin, ❝ ❝ can [TRT, RTR] be a substitute for RTRT or TRTR, or TTRR or RRTT (in four period fully replicated design)? ❝ Hey! Look at the fresh FDA draft ❝ Bloody partial replicate goes away and is being substituted to that design in GL. Yes and no. The partial replicate was nowhere mentioned in the previous (2001) guidance. On page 8 (after the 2-sequence 4-period full replicate) we read: Other replicated crossover designs are possible. For example, a three-period design, as shown below, could be used. $$\small{\begin{array}{rcccc}& & & \text{Period}\\\\ & & 1 & 2 & 3\\\\ & 1 & \textbf{T} & \textbf{R} & \textbf{T}\\ \text{Sequence}\\ & 2 & \textbf{R} & \textbf{T} & \textbf{R} \end{array}}$$ However, the partial replicate (and not the TRT|RTR) is still stated in the ANDA draft… ❝ I would opt for it. So would I. Not at least because of the nasty issues of the partial replicate in A. — 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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Brus ★ Spain, 2023-03-14 11:10 (639 d 18:58 ago) @ Sereng Posting: # 23498 Views: 4,310 |
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Dear Sereng, From my understanding, this is not a replicate study. 4-ways is not always a replicate. There can be 4 periods but with 4 different formulations, or in different administration conditions, and in those cases it would not be a "full replicate". In your case, according to my humble opinion it is not a "full replicate" since they are administered in different conditions (fast VS fed). In your case, I think it would be more accurate to call it "4-ways food effects". At least in our own previous experiences, this is the way we have approached it. Best regards, |
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Helmut ★★★ Vienna, Austria, 2023-03-14 11:37 (639 d 18:31 ago) @ Sereng Posting: # 23499 Views: 4,414 |
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Hi Sereng, ❝ … my associate is using the term "full replicate" to describe a four-way crossover BE study of Test (Fed), Test (Fasted), Reference (Fed) and Reference (Fasted), with each treatment given only once. In my view, this is not an appropriate us of the term "full replicate" but I want to be certain. You are right. For some of the designs see the vignette of the R package replicateBE.For the named food-interaction study you have three options. Primarily you are interested to demonstrate BE in fasted and fed state. The assessment of food effects of test and reference is just ‘nice to know’.
Whilst #2 is popular, there are drawbacks. If variabilities in fasted and fed state are different (commonly fed > fasted), you have to base the sample size on the worst case. #3 is for the courageous ones (though all of my studies were accepted by European agencies ). Both parts (fed and fasting) are TSDs like in #1. You start with a best guess sample size for the condition with lower variability. Food effects can by assessed as paired comparisons (assuming identical period effects), which is much more powerful than the parallel comparison in #1.❝ Additionally, what is the appropriate term, "Full Replicate" or "Fully Replicate"? You can either say “full replicate design” or “fully replicated design”. In the former term you use an adjective and in the latter adverbs. — 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 |
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Sereng ☆ USA, 2023-03-14 21:08 (639 d 09:00 ago) @ Helmut Posting: # 23500 Views: 4,290 |
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Hi Helmut, you are a Godsend! BTW, have you considered monetizing this site, even if it is for a modest one-time or annual subscription fee? This could also help you with resource allocation. Just a thought...... Regards — Biostatistically Challenged CEO |
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Relaxation ★ Germany, 2023-03-20 09:56 (633 d 20:12 ago) @ Helmut Posting: # 23506 Views: 4,104 |
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Hi everybody and sorry for posting this additional question late. But I cannot get to a clear answer by myself. Helmut, you stated ❝ What you must not use is the Latin Square ABCD|BCDA|CDAB|DABC. Only from a Williams’ design you can extract balanced pairwise comparisons I somehow fail to see why the extracted "pairs" are not considered balanced. They are not balanced for carry-over (which was always the most important reason for Williams), but aren't they for period and sequence? Is this what you mean here? I have no idea how to make it fancy, so I will try an ASCII-style Sequence | Treatments | IBD for A vs B So A is present once in each sequence and period and the same for B. Best regards, Relaxation. |
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mittyri ★★ Russia, 2023-03-28 01:01 (626 d 06:07 ago) @ Relaxation Posting: # 23515 Views: 3,924 |
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Dear Relaxation! let me cite the classical book written by Byron Jones and Michael G. Kenward: ❝ Although this design has maximum efficiency in the absence of carry-over effects, it is not as efficient at estimating the direct treatment effects as it could be. To achieve the highest possible efficiency the design must be balanced. The term balance refers to the combinatorial properties that the design must possess. In a balanced design, not only does each treatment occur once with each subject, but, over the whole design each treatment occurs the same number of times in each period and the number of subjects who receive treatment i in some period followed by treatment j in the next period is the same for all i != j. The design in Table 4.1[Latin square] is not balanced because treatment A is followed three times by treatment B and treatment B is never followed by treatment A. — Kind regards, Mittyri |
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Helmut ★★★ Vienna, Austria, 2023-04-21 12:01 (601 d 19:07 ago) @ Relaxation Posting: # 23533 Views: 3,294 |
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Hi Relaxation, ❝ Hi everybody and sorry for posting this additional question late. I’m also sorry for replying that late. Somehow I missed your post. ❝ Helmut, you stated ❝ ❝ What you must not use is the Latin Square ABCD|BCDA|CDAB|DABC. Only from a Williams’ design you can extract balanced pairwise comparisons ❝ ❝ I somehow fail to see why the extracted "pairs" are not considered balanced. ❝ They are not balanced for carry-over […] Is this what you mean here? Yes. Three times A → B and once B → A. — 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