Yeah, so we looked at the collateral score, and so collateral score and outcomes in ESCAPE-MeVO were very strongly associated, but there was only a weak treatment effect modification, meaning collaterals could very well tell you if the patient does well or not, irrespective of treatment, but the ability to predict benefit of treatment of thrombectomy in that case was there, but it was weak. Nevertheless, I think that’s an important signal...
Yeah, so we looked at the collateral score, and so collateral score and outcomes in ESCAPE-MeVO were very strongly associated, but there was only a weak treatment effect modification, meaning collaterals could very well tell you if the patient does well or not, irrespective of treatment, but the ability to predict benefit of treatment of thrombectomy in that case was there, but it was weak. Nevertheless, I think that’s an important signal. The trial was not powered to detect these interaction effects. So the fact that we found one, despite the relatively small patient numbers, I think means that there is something there. And also just the qualitative effect, looking at the different subgroups where patients with poor collateral status were actually harmed by thrombectomy, it seems patients with good collateral status, they clearly benefited. And there was a mild benefit in those with moderate status. So that makes biological sense as well, because collaterals help to keep the brain alive over time. And you can imagine recanalizing that brain is just like a recipe for disaster almost. So that makes the, explains the kind of harm in the poor collateral status patients. In addition to that, there are a few other hints towards treatment effect modification from other trials. So we did find one with time, which was actually much clearer than the collateral effect modification where early treated patients seem to benefit from thrombectomy. The later treated patients didn’t. And there’s also some data from the other trials, like the DISTAL trial and the ORIENTAL-MeVO trial, that patients with higher NIHSS, so with more severe strokes, seem to benefit. And that makes total sense again, because if the patient doesn’t have any deficits to begin with, well, then what are you treating? So that makes sense. And I think taking all these things together and then wrapping that up in a modern trial design with adaptive enrichment rules that is able to, a trial that’s enabled to enrich by NIHSS, for example, symptom severity and by time, and then even incorporating intra-arterial thrombolytics into that trial to improve recanalization status. I think that will eventually be the best shot at proving thrombectomy benefit in acute patients. And we are actually starting a trial on that. So that’s hopefully starting in early next year or hopefully December this year. And I think the Swiss group is working on a similar trial. So I think people are thinking about how to tackle this.
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