Quentin Anstee joins Stephen Harrison, Jörn Schattenberg, Louise Campbell, and Roger Green to share recently developed insights about NITs and what the clinical trial best practices around them should be. Quentin started by offering five key takeaways from his recent talks at The Liver Forum and ICFL in Vienna
(1) As we have discussed on this podcast and elsewhere, trial endpoints around balloon hepatocytes are, in Quentin’s words, “not sufficiently robust.” (2) Rapidly attaining response from a given test (ALT, for example) is not necessarily a guarantee of early efficacy. (3) “Simple indirect biomarker panels like FIB-4” need to be interpreted with caution. (4) Since we do not have a single perfect gold standard test (neither histological nor non-invasive), we should consider a standard for clinical trial assessment that is a composite of multiple different types of tests, perhaps one liquid, one physical (MRE?) and one histological. Finally, (5) We need to develop a battery of NITs that are both applied and reported in all cases, instead of running large numbers of NITs and only reporting the ones that support the targeted medication.
This stimulating set of opening comments motivates the group to dive deeply into the entire issue of how we deploy and analyze NITs. One key question is longitudinal. Quentin points out that early response to a composite test (like FIB-4) might not suggest endpoint efficacy over time. Similar to this, it also suggests that a positive 26-week result in a composite or liquid test might not mean much if the drop comes in the first couple of weeks and then maintains the lower level the next few months. This leads Stephen to suggest that researchers evaluate change at three levels: early change, late change, and sustained change. It also leads to a discussion of “stacking” tests so that a respondent would need to achieve multiple successful test scores for the researcher to be confident that the patient’s response is positive.
These are only a few insights from a far larger set that emerges during this discussion. Dive in for yourself to see what you find most intriguing.