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Averroes ☆ Spain, 2014-03-31 19:48 (4058 d 10:47 ago) Posting: # 12744 Views: 5,038 |
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Dear all, One of my colleagues recently have performed a pilot study with alendronate (N=12), measuring alendronate in plasma, and results showed a CV intra of >50% for both Cmax and AUC, while CV intra described in literature is not so high (around 36-38%). When reviewing the design of that study I found that sampling points were not as frequent as they should be (they were +0.50 h, +1.00 h, +1.50 h, +2.00 h,...) but I found more appropiate a frequency of 0.25h during the first 2 h in order to charactherize Cmax properly. Do you think poor frequency of blood sampling could have influenced CV intra? Thanks, Edit: Category changed. [Helmut] |
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Helmut ★★★   Vienna, Austria, 2014-04-01 02:54 (4058 d 03:41 ago) @ Averroes Posting: # 12747 Views: 4,211 |
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¡Hola Averroes! ❝ Do you think poor frequency of blood sampling could have influenced CV intra? Absolutely! Like all bisposphonates alendronate has (very!) low and highly variable absorption, spiced with lag-times. With too few sampling time points we might get a biased estimates of the Cmax-ratio in individual subjects. Regularly missing the ‘true’ Cmax directly translates into an increased CVintra. See this example (slides 44–45). Now your colleague learned the hard way one of the purposes of a pilot study (nicely outlined by the ![[image]](img/uploaded/IAsmall.png) FDA):[…] a pilot study in a small number of subjects […] can be used to validate analytical methodology, assess variability, optimize sample collection time intervals, and provide other information. For example, for conventional immediate-release products, careful timing of initial samples may avoid a subsequent finding in a full-scale study that the first sample collection occurs after the plasma concentration peak. For modified-release products, a pilot study can help determine the sampling schedule to assess lag time and dose dumping. (my emphasis)BTW, since alendronate is well known to be a HVD, n=12 is too small by far – if he/she wanted to get reliable estimates of the ratios and CVs for sample size estimation. IMHO, alendronate would be a candidate for reference-scaling (ABEL). In that case the pilot study should be performed in a replicate design. — 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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Averroes ☆ Spain, 2014-04-03 03:09 (4056 d 03:25 ago) @ Helmut Posting: # 12761 Views: 4,041 |
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Dear Helmut, Thanks so much for your comments, I totally agree. Another item to add in our lesson learned list. I would like to take the opportunity to thanks also for this helpful forum. BTW, I will be attending the Budapest event in May, hope we could meet in person. Thanks! |
Ing. Helmut Schütz