Therapeutic Product Immunogenicity Community

Dear community members, 

For an ADA assay, we had to set screening cutpoint based on normal population with 5% FPR during validation. However, in the clinical trial in the disease population matrix we are observing a 13% FPR rate. 

Is this okay when the recommendation is 5% FPR?  What is your experience with a similar issue?

Other than having to analyze more samples in the confirmatory tier, are there regulatory risks to having a higher FPR rate?   What is your technical perspective?  Will there be questions on the technicalities of the method? Is an in-study cut point required?

Thank you!

Hi! I have seen this happen before and we interpreted it as you said below. There's no 'upper limit' on the FPR in the guidance docs that I've seen since essentially, it's just leading to more effort on your part to analyze more samples than necessary in the confirmatory tier. I think it's basically a resource use question for you: if this is a small study, then perhaps leave it as is...if it's a rather large study, may want to re-evaluate. If deciding to leave as is, then there's a reduced risk of missing potentially positive samples as a possible upside.

Dear community members, 

For an ADA assay, we had to set screening cutpoint based on normal population with 5% FPR during validation. However, in the clinical trial in the disease population matrix we are observing a 13% FPR rate. 

Is this okay when the recommendation is 5% FPR?  What is your experience with a similar issue?

Other than having to analyze more samples in the confirmatory tier, are there regulatory risks to having a higher FPR rate?   What is your technical perspective?  Will there be questions on the technicalities of the method? Is an in-study cut point required?

Thank you!