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jag009 ★★★ NJ, 2013-08-19 22:40 (3895 d 09:08 ago) Posting: # 11308 Views: 7,589 |
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Hi all, Apparently not... Question. If a study requires partial AUC at early phase of the plasma concentration-time curve, is it acceptable to implement in the protocol "Subject will be removed from the study if more than x blood draws cannot be collected within x min of schedule time during post-dose 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4 hours?" Given the fact that the variability of PAUC can be high, can the above be implemented at all? I know it probably doesn't happen but... Obvious with the above example, the subject will be dropped out if he/she misses the 4 hr sample since PAUC0-4 requires 4 hour timepoint. My answer to my questio? "As long as you state it in the protocol" Why I asked? Tada, some CRO managed to screw up some early timepoint collection by as much as 35mins!  Thanks John Edit: Category changed. [Helmut] |
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Helmut ★★★   Vienna, Austria, 2013-08-20 17:43 (3894 d 14:05 ago) @ jag009 Posting: # 11322 Views: 6,179 |
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Hi John, ❝ Apparently not... Otherwise it would be boring, isn’t it? ❝ Question. If a study requires partial AUC at early phase of the plasma concentration-time curve, is it acceptable to implement in the protocol "Subject will be removed from the study if more than x blood draws cannot be collected within x min of schedule time during post-dose 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4 hours?" Maybe; actually no qualified opinion.  ❝ Given the fact that the variability of PAUC can be high, can the above be implemented at all? Again – maybe. You will loose power what you terribly need for this metric… ❝ Obvious with the above example, the subject will be dropped out if he/she misses the 4 hr sample since PAUC0-4 requires 4 hour timepoint. ❝ ❝ […] Tada, some CRO managed to screw up some early timepoint collection by as much as 35mins! That’s a fucking lot! What happened? Normaly time deviations outside an “allowance window” stated in the protocol must be not only documented as such but also a comment in the CRF should be given justifiying the event. 35min?! BTW, if you ask Phoenix/WinNonlin for partial AUCs (and sampling wasn’t performed exactly at the cut-off time point) an interpolation between two adjacent time points (before/after) is used; linear if C2 ≥ C1 and log/linear if C2 < C1. Makes sense, IMHO. — 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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jag009 ★★★ NJ, 2013-08-20 20:09 (3894 d 11:38 ago) @ Helmut Posting: # 11323 Views: 5,987 |
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Hi Helmut! ❝ ❝ […] Tada, some CRO managed to screw up some early timepoint collection by as much as 35mins! ❝ ❝ That’s a fucking lot! What happened? Normaly time deviations outside an “allowance window” stated in the protocol must be not only documented as such but also a comment in the CRF should be given justifiying the event. 35min?! 4 out of 30 subjects had this fiasco. Get this one --> Sampling time at 3.5 and 4.0 hour... They were late 35 mins for the 3.5 (meaning it crossed over into the 4 hr timepoint). They then draw a 4 hr timepint sample with a delay of 11 mins (It's obvious why, they didn't want to miss collecting a sample!!!)So now I have a 3.5hr sample with a +35min deviation and a 4 hr with a +11min deviation!!! what should I use for PAUC0-4?????? Reason for deviation? Couldn't get blood from sites of puncture! 35mins!???? how many time did they poke on the subjects arm(s)!!!!! I wouldn't have gone ballistic if the reason was "Subject went into hiding somewhere in the dosing area" |
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Helmut ★★★ Vienna, Austria, 2013-08-20 20:16 (3894 d 11:31 ago) @ jag009 Posting: # 11325 Views: 6,013 |
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Hi John! ❝ 4 out of 30 subjects had this fiasco. Very strange, indeed! ❝ So now I have a 3.5hr sample with a +35min deviation and a 4 hr with a +11min deviation!!! what should I use for PAUC0-4?????? If you want you can post the time course of this subject (scheduled & actual times, concentrations). Let’s see. ❝ Reason for deviation? Couldn't get blood from sites of puncture! 35mins!???? how many time did they poke on the subjects arm(s)!!!!! Do you believe in this “reason”? ❝ I wouldn't have gone ballistic if the reason was "Subject went into hiding somewhere in the dosing area"  — 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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jag009 ★★★ NJ, 2013-08-20 20:19 (3894 d 11:28 ago) @ Helmut Posting: # 11326 Views: 5,985 |
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Hi Helmut, ❝ If you want you can post the time course of this subject (scheduled & actual times, concentrations). Let’s see. Study is in progress with period 1 completed... Will update. ❝ ❝ Reason for deviation? Couldn't get blood from sites of puncture! 35mins!???? how many time did they poke on the subjects arm(s)!!!!! ❝ Do you believe in this “reason”? What can I do? ❝ ❝ I wouldn't have gone ballistic if the reason was "Subject went into hiding somewhere in the dosing area" Playing hide and seek with the person holding needle... John |
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Helmut ★★★ Vienna, Austria, 2013-08-20 20:34 (3894 d 11:14 ago) @ jag009 Posting: # 11327 Views: 6,043 |
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Hi John, ❝ ❝ ❝ Reason for deviation? Couldn't get blood from sites of puncture! 35mins!???? how many time did they poke on the subjects arm(s)!!!!! ❝ ❝ Do you believe in this “reason”? ❝ ❝ What can I do? Likely nothing. If you audit the site now, which answer do you expect? Even if they come up with something (relying on their memory “Oops, I remember it was just five minutes late, not 35. Sorry!”) – will it be more credible than was written (GCP…) in the CRF? Fishy. Whenever possible monitor at least the first period of all studies. — 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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jag009 ★★★ NJ, 2013-08-20 21:54 (3894 d 09:53 ago) @ Helmut Posting: # 11330 Views: 5,924 |
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Hi Helmut, ❝ Likely nothing. If you audit the site now, which answer do you expect? Even if they come up with something (relying on their memory “Oops, I remember it was just five minutes late, not 35. Sorry!”) – will it be more credible than was written (GCP…) in the CRF? Fishy. ❝ Whenever possible monitor at least the first period of all studies. The joke of the day... My monitor was there but left after 3 hours because she was satisfied with the performance observed during her stay (-1 day upto 3 hour post-dose draw). |
Ing. Helmut Schütz