From Gilead Page:
HARVONI was administered once daily by mouth in these trials. Sustained virologic response (SVR12) was the primary endpoint and was defined as HCV RNA less than LLOQ at 12 weeks after the cessation of treatment.
Thank you, Enkel, for pointing out (post#7415 on this thread and some other posts on other threads) that SVR12 is, apparently, not limited, as I had previously thought, to being HCV RNA undetected at 12 weeks after the last dose of treatment. Thanks also for backing this up with the quote above from a Gilead document which states that the definition of SVR12 used for the ION clinical trials into Harvoni (sof/led) was being below the LLOQ (Lowest Limit of Quantification) at 12 weeks post EOT (end of treatment). I assume that if this is the meaning of SVR12 used by Gilead in the ION trials it must be a meaning which is accepted not just by Gilead but also by the wider medical and scientific community.
It seems to me, if my understanding is correct, that, potentially at least, being below the LLOQ is not quite the same thing as being undetected at 12 weeks post-EOT (although clearly it includes being undetected at 12 weeks post-EOT). Is this correct? For example, does being below LLOQ for this purpose include being <LLOQ DETECTED as well as being <LLOQ UND at 12 weeks post-EOT?
This question isn't answered by the quote (above) Enkel provides from the Gilead document.
So, is the upshot of this that while the meaning of SVR12 includes being undetected at 12/52 (i.e. 12 weeks) post-EOT it is not limited to it? The meaning of SVR12 used by Gilead (above) seems to be a little more forgiving than this. It also includes having HCV RNA below the LLOQ (Lowest Limit of Quantification) at 12/52 post-EOT, which may also include, although I am not sure about this and I stand to be subsequently corrected here, being below LLOQ DETECTED.
This question may have practical implications. For example, does it mean that the best VL test to do at 12/52 post-EOT may be quantitative and not qualitative? The qualitative test is more precise at very low levels of HCV RNA but might it not also be too strict for the purpose of establishing the broader, more lenient definition of SVR12 given in the quote above? My understanding is that the qualitative test is reported simply as either detected or undetected. If this is so, then although the qualitative VL test is best for determining the more strict definition of SVR12 it would fail to identify the lenient definition of SVR12 because it cannot distinguish the result <LLOQ DETECTED, and hence potentially at least (depending on the answer to my question above) still within SVR12, from any result equal to or >LLOQ, which would constitute relapse and failure to attain SVR12.
Another thing that puzzles me about this more lenient definition of SVR12 is that if someone achieves UND at EOT but then their VL test comes back <LLOQ DETECTED at 12/52 post-EOT does this still amount to SVR12? They are below LLOQ at 12/52 but the direction of change in their VL load seems to be going the wrong way – it's getting worse, not better.