I have seen and done it multiple ways.
For before sample analysis, I have also seen it limited to the first X participants so that you can get an in-study cut point factor before too much time passes. Since immunogenicity testing is typically done in larger batches, this really depends on the enrollment speed of your study.
I have seen the second approach used much more in oncology trials for orphan cancer indications. Those studies can enroll very slowly so it can take a while before you get enough baseline samples. In that case, I have had the lab reprocess all the data with the new cut point factors. If the cut point factor goes down, it is pretty straightforward because you put more samples into the confirmation tier. If the cut point factor goes up, then you have a number of samples that were now put through confirmation and potentially titration that are now screen negative. If the confirmation step was negative, then it is typically masked. If zero or a few confirmation were positive, then the titration result would still be reported under a deviation so as to not under report. If there are a lot of confirmation positive, then I'd say you have evidence that supports to continue using the original cut point factor from validation rather than the study-specific cut point factor.
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Joleen White Ph.D.
AAPS 2023 Global Health Community Past Chair
Bioanalytical 101 Course Development
Head of Bioassay Development
Gates Medical Research Institute
Cambridge MA
[email protected]Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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Original Message:
Sent: 03-28-2023 21:17
From: Ritankar Majumdar
Subject: When to perform the in-study cut point evaluation?
Hi Ngoc,
Wouldnt the determination of when the in-study cut point should be evaluated depending on whether a sufficient number of pre-dose individuals have been screened and enrolled into the clinical study? In most case, this condition is not fulfilled in option 1.
Ritankar.
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Ritankar Majumdar
Senior Lead Scientist
Covance Inc. - Chantilly, Va
Chantilly VA
[email protected]
Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
Original Message:
Sent: 03-18-2023 17:12
From: Ngoc Pham
Subject: When to perform the in-study cut point evaluation?
The question is posted on behalf of the member(s) from the Early Career Bioanalytical Subteam (ECBS):
When should we perform the in-study cut point evaluation?
Option 1: before the sample testing: ISCPs may end up very close to validation CPs (i.e. not necessary to establish ISCPs).
Option 2: during the sample testing: if a new set of CPs was established, previously generated data would then be changed. How should we monitor this process if the data has been delivered to the clinical team?
We look forward to receiving the inputs from the community! Thank you.
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Ngoc Pham
Senior Scientist
Merck & Co
West Point PA
[email protected]
Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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