Yura
★    

Belarus,
2016-11-09 10:10
(2716 d 17:16 ago)

Posting: # 16790
Views: 6,466
 

 Design HVDP [Design Issues]

Dear all
Can I use design RTR | TRR for highly variable drugs?:-|

Thanks and regards
d_labes
★★★

Berlin, Germany,
2016-11-09 13:01
(2716 d 14:26 ago)

@ Yura
Posting: # 16791
Views: 5,691
 

 extra-reference design

Dear Yura

❝ Can I use design RTR | TRR for highly variable drugs?:-|


see this post and linked post within it. Search also the forum for "extra-reference design".

Like Helmut I would not recommend this design, although it allows the estimation of the variability of the Reference and should therefore suitable for the evaluation via scaled ABE.
Since the Test is never administered in period 3 I would expect difficulties if there is a period effect.
Moreover the partial replicate design with sequences TRR|RTR|RRT is meanwhile the de facto standard if one goes with a three period design in evaluating scaled ABE for HVD/HVDP.

Regards,

Detlew
Yura
★    

Belarus,
2016-11-10 13:18
(2715 d 14:08 ago)

@ d_labes
Posting: # 16794
Views: 5,529
 

 extra-reference design

thank you very much Dear d_labes
There was information in presentation about higt importance of sequence effect and toughening of level of its significance up to 0,1 (instead of 0,05) i. e. the effect of the period can be ignored
Kind regards
Helmut
★★★
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Vienna, Austria,
2016-11-10 14:28
(2715 d 12:58 ago)

@ Yura
Posting: # 16795
Views: 5,595
 

 extra-reference design

Hi Yura,

❝ There was information in presentation …


May I ask: Which presentation?

❝ … about higt importance of sequence effect and toughening of level of its significance up to 0,1 (instead of 0,05) i. e. the effect of the period can be ignored


α 0.1 was suggested in the past because of the low power of the test (between subjects). But:
  • Testing for a sequence effect (or better: unequal carry-over) is flawed and should be abandoned (see this post and references).
  • Testing for a period effect is futile as well. A period effect means out in cross-over studies (unless sequences are extremely (‼) unbalanced). As Detlew wrote above, a true period effect may give a biased treatment estimate in the extra-reference design. Therefore, it should not be used.

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Yura
★    

Belarus,
2016-11-10 14:49
(2715 d 12:37 ago)

@ Helmut
Posting: # 16796
Views: 5,534
 

 extra-reference design

thank you very much Dear Helmut
mittyri
★★  

Russia,
2016-11-09 13:13
(2716 d 14:13 ago)

@ Yura
Posting: # 16792
Views: 5,546
 

 Design HVDP

Dear Yura,

Radio Yerevan’s answer:
“In principle yes, but you have to demonstrate very strong reasons not to use recommended one.”

Kind regards,
Mittyri
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